Tissue-engineered heart valves.

Currently-used mechanical and biological heart valve prostheses have several disadvantages. Mechanical prostheses, based on carbon, metallic and polymeric components, require permanent anticoagulation treatment, and their usage often leads to adverse reactions, e.g. thromboembolic complications and endocarditis. Xenogenous and allogenous biological prostheses are associated with immune reaction, thrombosis and degeneration, and thus they have a high rate of reoperation. Biological prostheses of autologous origin, such as pulmonary autografts, often burden the patient with a complicated surgery and the risk of reoperation. Therefore, efforts are being made to prepare bioartificial heart valves with an autologous biological component by methods of tissue engineering. They should be biocompatible, durable, endowed with appropriate mechanical properties and able to grow with a child. For this purpose, scaffolds composed of synthetic materials, such as poly(lactic acid), poly(caprolactone), poly(4-hydroxybutyrate), hydrogels or natural polymers, e.g. collagen, elastin, fibrin or hyaluronic acid, have been seeded with autologous differentiated, progenitor or stem cells. Promising results have been obtained with nanostructured scaffolds, and also with cultivation in special dynamic bioreactors prior to implantation of the bioartificial grafts into an animal organism.

Expression of cyclin D1, Ki-67 and PCNA in non-small cell lung cancer: prognostic significance and comparison with p53 and bcl-2.

Uncontrolled cell proliferation is the hallmark of malignant tumours. Thus, the proliferative potential of tumour cells is an important prognostic factor. However, evaluation of the prognostic significance of the expression of proteins involved in regulation of cell proliferation remains controversial. In the present study, expression of Ki-67, PCNA and cyclin D1 was estimated in a group of 89 surgically resected non-small cell lung carcinomas using immunohistochemistry. The results were compared with expression of bcl-2 and p53 and with clinicopathological parameters including patients' survival. Ki-67 and PCNA were found to be moderately and highly expressed in 39% and 44% of the tumours, respectively. There was a strong correlation between Ki67 and PCNA expression. Forty five of 88 tumours (51%) showed overexpression of cyclin D1. Surprisingly, cyclin D1 was mainly localized in the cytoplasm and only a small group of tumours (9/88, 10%) showed nuclear staining as well. Bcl-2 and p53 expression was observed in 69% and 30% of the tumours, respectively. All these markers were found to be independent of clinicopathological parameters, except for Ki-67 and bcl-2 expression, which was associated with squamous cell carcinomas. It is concluded that none of the markers that were studied can be used as an independent prognostic factor, whereas the following combinations of markers may have favourable prognostic value: p53 positivity and low Ki-67 expression, p53 positivity and lack of cyclin D1 expression, bcl-2 positivity and low Ki-67 expression, and lack of cyclin D1 expression and low Ki-67 expression.

CD44 and its v6 spliced variant in lung carcinomas: relation to NCAM, CEA, EMA and UP1 and prognostic significance.

CD44 is a polymorphic family of cell surface glycoproteins that was recently reported to have important role in cell adhesion and migration as well as modulation of cell-matrix interactions. Thus, expression of CD44 has been proposed to be associated with malignant behavior of tumors like invasive growth and formation of metastasis. The expression of CD44s and its v6 isoform (CD44v6) was determined immunohistochemically in 106 lung tumors of various histophenotypes, degrees of differentiation, and clinical stages. The results were compared with the expression of NCAM, CEA, EMA and UP1 and with clinicopathological parameters including patients' survival. CD44s was expressed in all histophenotypes of non-small cell lung carcinomas (NSCLC) with tendency being squamous cell lung carcinoma (SqCC) > bronchioloalveolar adenocarcinoma (BAC) > conventional adenocarcinoma (ConAC) (91, 66.7 and 38.9%, respectively). Almost identical distribution of positivity revealed CD44v6 in all three subgroups of NSCLC mentioned above (91, 66.7 and 36.1%, respectively). In the subgroup of neuroendocrine tumors, CD44s and CD44v6 were restrictedly expressed in small cell lung carcinomas (2/14 tumors), while all 3 typical carcinoids were strongly positive for these markers. Expression of NCAM and CEA was significantly higher in adenocarcinoma subgroup than those in SqCC subgroup (45.7 and 75% vs. 14.8 and 39%, respectively). NCAM expression was also significantly different in BACs and in ConACs (69.2 vs. 36.4%, p < 0.05). The expression of CD44 was related to the differentiation of SqCC. The carcinomas with keratinization were CD44 positive. Adenocarcinomas producing mucin were CD44 negative. The expression of CD44, NCAM, CEA, EMA and UP1 did not correlate with lymph node metastasis and disease stage. CD44V6 was the only marker that its expression was closely related to patients' survival. The absence CD44v6 but not CD44s in NSCLC group was associated with significantly longer survival of patients compared to patients with CD44v6 positive tumors. This difference was even higher in tumors negative for CD44v6 and simultaneously NCAM and/or CEA positive. The data of this study suggest that CD44v6 might be an independent prognostic factor in NSCLC. Moreover, our data give another evidence of diverse role of CD44 in the differentiation and progression of non-small cell lung carcinomas and neuroendocrine carcinomas of the lung.

Cytokeratins and lung carcinomas.

BACKGROUND: Recently, cytokeratins (CK) were studied as tumor markers for many carcinomas. In lung cancer they appeared to be useful in distinguishing primary from secondary tumors, in histological typing as well as in evaluating patient's prognosis. However, the results have yet to be conclusive. In this study, expression of CK7, CK10/13, CK18, CK19, CK20 was investigated in a group of 72 surgically resected specimens of lung including 31 adenocarcinomas, 30 squamous cell carcinomas and 11 neuroendocrine carcinomas. Cytokeratin immunophenotypes were analyzed in comparison to histological characteristics of tumors, TNM stages and patients survival. RESULTS: CK7, CK10/13 and CK18 can be used in distinguishing the lung adenocarcinomas from the lung squamous cell carcinomas: CK7(+), CK10/13(-), CK18(+) for adenocarcinomas; CK7(-), CK10/13(+), CK18(-) for squamous cell carcinomas. Relatively higher CK7 and CK18 immunostaining rates of the squamous cell carcinomas with high keratinization, with high percentage of dead cells and with late stages of disease suggested their prognostic significance but it was not confirmed when comparing different survival groups. Both adenocarcinomas and squamous cell carcinomas were stained strongly with antibody against CK19 (90.3% and 86.7% respectively) but much less with anti-CK20 antibody (9.7% and 3.3% respectively). In general, neuroendocrine tumors of the lung were non-reactive for these cytokeratins except CK18, among them all carcinoid tumors expressed CK18 abundantly.

[Expression of p53, p21 and bcl-2 in prognosis of lung carcinomas]. / Exprese p53, p21 a bcl-2 v prognostice plicních karcinomu.

Expression of suppressor genes 53 and bcl-2 as well as of protein p21 (partly induced by p53 gene) was analyzed in a group of 77 resection specimens and bronchial excision of lung carcinomas (of all basic histological types--squamous cell, neuroendocrine, adenocarcinoma, undifferentiated). Simultaneously the relation of tumor immunophenotype and level of differentiation, cell death and 2-year-survival of patients was evaluated. Gene p53 showed non-only an expected strong expression in squamous cell carcinomas but especially in adenocarcinomas, which were newly characterized by exceptional hyper-expression of p53 in lowly differentiated variants. Expression level of protein p21 and gene p53 was parallel only in adenocarcinomas and undifferentiated carcinomas but discordant in squamous cell and neuroendocrine carcinomas. Positivity of p21 slightly prevailed in well-differentiated variants of the histological types but an exceptional positivity was found even in all the undifferentiated carcinomas. Gene bcl-2 revealed a paradox of strong expression in lowly differentiated neuroendocrine and undifferentiated carcinomas. The level of bcl-2 expression in squamous cell carcinomas was found higher than in references. Among tumors with cell death there was an inverted relation of bcl-2 and p53 expression (high/low) in neuroendocrine carcinomas but both of them were mostly negative in squamous cell carcinomas. A more frequent 2-year-survival of squamous cell carcinomas was verified for bcl-2 positive tumors and newly for p53 positive squamous cell carcinomas. Evaluation of the expression of p53, p21 and bcl-2 in lung carcinomas is so equivocal that its prognostic usage was found to be only complementary to the direct immunohistochemical investigation of the growth activities.

[Expression of the nm 23 gene in pulmonary carcinomas]. / Exprese genu nm 23 v plicních karcinomech.

Gene nm 23 may have an antimetastatic function but relevant data in the literature are ambiguous even in the same types of malignant tumors. In a group of 77 lung carcinomas there was not found any relation of gene nm 23 expression to the histologic type of tumor or the level of its differentiation and to the finding of metastases in resected lung materials either. Adenocarcinomas showed a negative relation of nm 23 expression to later occurrence of metastases and to a decreased survival of patients which squamous, neuroendocrine and undifferentiated carcinomas did not. Unexpected low expression or negativity of nm 23 in tumors of little progression and rare high positivities in some lung carcinomas with metastases could be explained by gene nm 23 mutations or inactivation. Results of the study do not encourage the usage of nm 23 as a reliable prognostic marker in lung carcinomas.

[Sarcomatous hepatocellular carcinoma]. / Sarkomatoidní hepatocelulární karcinomy.

Atypical variants of liver carcinomas may represent diagnostic pitfalls when compared with classical types. We described two cases of unusual hepatocellular carcinoma with sarcomatoid pattern. Both were large tumors in elderly people. Their immunohistochemical investigation showed a coexpression of various epithelial and mesenchymal markers. There were positivities of antibodies against cytokeratin, actin and desmin in the first case, against cytokeratin, chromogranin and actin in the second case and against EMA and A1AT in both of them. Such a tumor was not found either in five year bioptic and four year necroptic archival material or in the Hlava Institute histopathological collection. The frequency of the tumor was about 4% of all hepatocellular carcinomas according to the literature.