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Biomedical subjects

A Szadowska

Publications and source records attributed to A Szadowska.

At least 19 recordsLinked to original sources
PubMed2001

Clinical impact of molecular and cytogenetic findings in synovial sarcoma.

Synovial sarcoma is an aggressive soft-tissue tumor that accounts for up to 10% of soft-tissue sarcomas. Cytogenetically, synovial sarcoma is characterized by the t(X;18)(p11;q11), found in more than 95% of the tumors. This translocation results in rearrangements of the SYT gene in 18q11 and one of the SSX1, SSX2, or SSX4 genes in Xp11, creating a SYT/SSX1, SYT/SSX2, or SYT/SSX4 chimeric gene. It has been shown that patients with SYT/SSX1 fusion genes have a shorter metastasis-free survival than do patients with SYT/SSX2. Previous studies have also suggested that clonal evolution may be associated with disease progression. In the present study, RT-PCR analysis showed that all 64 examined synovial sarcomas from 54 patients had SYT-SSX chimeric genes. SYT/SSX1 was found in 40 tumors from 33 patients, SYT/SSX2 in 23 tumors from 20 patients, and SYT/SSX4 in one case. Two patients had variant SYT/SSX2 transcripts, with 57 bp and 141 bp inserts, respectively, between the known SYT and SSX2 sequences. Patients with tumors with SYT/SSX1 fusions had a higher risk of developing metastases compared to those with SYT/SSX2 fusions (P = 0.01). The reciprocal transcripts SSX1/SYT and SSX2/SYT were detected using nested PCR in 11 of the 40 samples with SYT/SSX1 and 5 of the 23 samples with SYT/SSX2, respectively. Among 20 blood samples, SYT/SSX1 and SYT/SSX2 were detected in one sample each. The t(X;18), or variants thereof, was found cytogenetically in all patients but three. Among 32 primary tumors, the t(X;18) or a variant translocation was the sole anomaly in 10. In contrast, of the seven metastatic lesions that were investigated prior to radiotherapy, only one had a t(X;18) as the sole anomaly; all other tumors displayed complex karyotypes. Cytogenetic complexity in primary tumors was, however, not associated with the development of metastases. Tumors with SYT/SSX2 less often (4/12 vs. 7/15) showed complex karyotypes than did tumors with SYT/SSX1, but the difference was not significant. Combining cytogenetic complexity and transcript data, we found that the subgroup of patients with tumors showing simple karyotypes and SYT/SSX2 fusion had the best clinical outcome (2/8 patients developed metastases), and those with tumors showing complex karyotypes together with SYT/SSX1 fusion the worst (6/7 patients developed metastases). This corresponded to 5-year metastasis-free survival rates of 0.58 and 0.0, respectively (P = 0.02).

Adolescent↗
PubMed2000

Serial transplants of DMBA-induced mammary tumors in fischer rats as model system for human breast cancer: V. Myoepithelial-mesenchymal conversion during passaging as possible cause for modulation of pineal-tumor interaction.

An elevation of melatonin secretion parallel to an enhanced production of macrophage-derived biopterin was observed in female F344 Fischer rats bearing passage 2 serial transplants derived from a malignant mammary tumor induced by 7,12-dimethylbenz[a]anthracene (DMBA). As opposed to that both parameters were depressed at passage 12. These results indicate the presence of divergent immunoneuroendocrine interactions during different phases of tumor growth. Since these biochemical events must have their common origin in changes taking place within these tumor transplants the current histopathological study was initiated. The primary tumor used for serial transplantation was a moderately differentiated adenocarcinoma of the mammary gland showing cytokeratin-positive epithelial components located in the inner epithelial tubule layer. In addition, bland-looking round or elongated actin-positive myoepithelial cells were detected which apart from epithelial cells are known to constitute the main cellular components of the mammary ductal system which resemble smooth muscle cells both morphologically and functionally. The tumor of passage 1 showed glandular tubules, lined by an inner epithelial layer, and many nests of clear, bland-looking actin-positive myoepithelial cells lying around tubules as well as in the stroma between actin-negative epithelial elements. The tumor of passage 2 used for transplantation consisted of a chaotic mixture of epithelial carcinomatous cells, forming a few irregular small tubules or solid nests, and, predominantly, of elongated plump or spindle-shaped, "myoid" atypical myoepithelial cells with a strong actin-positive reaction and some of these cells showed a focal vimentin expression. The tumor was characterized as a carcinosarcoma. At passage 12 epithelial cells were not identified. The tumor displayed features of a pleomorphic sarcoma consisting mainly of giant cells with bizarre nuclei being cytokeratin- and desmin-negative, weakly vimentin-positive but strongly actin-positive. These results indicate that DMBA-induced mammary tumor cells in female F344 Fischer rats undergo dramatic morphological changes during serial transplantation characterized by a total loss of malignant epithelial (carcinomatous) cells and the emergence and subsequent predominance of malignant (sarcomatous) mesenchymal cells. It appears that these sarcomatous cells develop out of myoepithelial cells since atypical myoepithelial cells with a strong actin-positive reaction showed a focal vimentin expression at passage 2 indicating myofibroblastic differentiation as part of mesenchymal transition. The loss of epithelial cell elements as well as a parallel transition of myoepithelial to mesenchymal cell elements during passaging could lead to a lack of immunological recognition of these tumor transplants and to depression of melatonin. Possible mechanisms involved in these phenomena as well as the relevance of these findings for a better understanding of the role of melatonin in human mammary cancer are discussed.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1999

Malignant fibrous histiocytomas and H-ras-1 oncogene point mutations.

AIMS: To investigate the types and the frequencies of H-ras-1 gene mutations in malignant fibrous histiocytomas. METHODS: Thirty five samples of malignant fibrous histiocytoma tissue were searched for point mutations within "hot spot" codons 12 and 13 of the H-ras-1 oncogene by the specific "nested" polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) and a direct cycle sequencing procedure. RESULTS: In contrast to previous reports, none of the tumours contained a point mutation or any other changes within or around the hot spot gene sequences. CONCLUSIONS: These data indicate that H-ras-1 oncogenic activation is not required in the molecular pathway of malignant fibrous histiocytoma formation and cannot be used as a discriminating factor for diagnostic sarcoma typing.

Exons↗
PubMed1999

Expression of P53, MDM2 and Ki-67 antigens in soft tissue sarcomas.

The expression of P53 and MDM2 proteins was examined by immunohistochemistry in 115 soft-tissue sarcomas (STSs), including 32 malignant peripheral nerve sheath tumours, 27 liposarcomas, 18 leiomyosarcomas, 16 synovial sarcomas, 14 fibrosarcomas and 8 dermatofibrosarcomas, to investigate their possible association with clinicopathologic features and proliferative rate. Positivity for P53 and MDM2 was found in 9.7% and 28.1% tumours, respectively. The fraction of P53 and MDM2 positive tumours was the highest in leiomyosarcomas (16.7% and 17.2%, respectively) and the lowest in dermatofibrosarcomas (0% and 4.3%, respectively). Overall, P53(-)/MDM2(+) phenotype predominated (20.2%), while 7.9% of tumours were both P53 and MDM2 positive, and 1.8% of tumours were only P53 positive. P53 accumulation was associated with a high histological malignancy grade and a higher proliferative rate. MDM2 immunoreactivity was revealed in tumours of all malignancy grades and there was no association between MDM2 positivity and tumours proliferative activity. These results suggest that P53 overexpression underlays rather late events in the oncogenesis of STSs, which might be a determinant of their proliferative rate. In contrast, MDM2 deregulation seems to be an early rather than a late event in STSs, which may occur without involving stabilization and inactivation of P53 gene.

Adult↗
PubMed1998

Recurrent chromosome changes in two adult fibrosarcomas.

Cytogenetic analysis of two adult fibrosarcomas revealed clonal chromosomal rearrangements including unbalanced translocations between chromosomes 2 and 19, with the same segment, 2q21-qter, translocated onto 19p13 in one tumor and 19q13 in another; and partial monosomy of 10q due to add(10)(q22) and del(10)(q22q25) seen in one tumor each. This is the first description of nonrandom chromosomal changes in adult fibrosarcoma.

Adolescent↗
PubMed1998

Immunohistochemical status of p53, mdm2 and Ki-67 in malignant fibrous histiocytoma.

The aim of the study was to evaluate the frequency of p53, mdm2 and Ki-67 immunopositivity in MFH, and to investigate possible associations of their expression with the grade of malignancy and predominant histological pattern--storiform, pleomorphic and myxoid subtype of MFH. A total number of 51 tumor samples from 21 primary and 30 secondary MFHs was studied using monoclonal anti-p53 (DO-78, DAKO), anti-mdm2 (1F2, NOVOCASTRA) and polyclonal anti-Ki-67 (DAKO) antibodies. The p53 immunopositivity was observed in 32.7% of all tumor samples (in 36.8% of primary and in 30% of recurrent and metastatic tumors). The mdm2 immunopositivity was noted in 34.8% of all tumor samples (in 33.3% of primary and 35.7% of secondary tumors). The mean percentage of p53, mdm2 and Ki-67 positive cells was 15.5, 8.8 and 7.05, respectively. The mean Ki-67 LI was statistically higher in grade 3 than in grade 2 of malignancy (p = 0.006). A significant correlation was found between mdm2 positivity and histological subtypes of MFH--storiform and pleomorphic types were more frequently mdm2 positive than myxoid variant (p = 0.035 and p = 0.009, respectively). No such correlation was observed for p53 positivity of tumors and subtypes, but there was a statistically significant difference in the percentage of p53 positive cells between storiform and myxoid type (p = 0.049). We also noted more tumors expressing high percentage (over 20%) of mdm2 positive cells in pleomorphic and storiform subtypes than in myxoid variant (p = 0.048). The Ki-67 LI was also higher in pleomorphic than in other types of MFH (p = 0.012). A strong positive correlation was found between p53 positivity and mdm2 positivity of tumors in primary MFHs (p = 0.00146). p53 and mdm2 positive tumors were mainly in grade 3 of malignancy, but no statistically significant correlations were noted. A positive correlation between the percentage of p53 positive cells and Ki-67 positive cells (p = 0.0028) was observed.

Histiocytoma, Benign Fibrous↗
PubMed1998

Detection of the SYT-SSX fusion transcripts in formaldehyde-fixed, paraffin-embedded tissue: a reverse transcription polymerase chain reaction amplification assay useful in the diagnosis of synovial sarcoma.

Identification of the t(X;18)(p11.2;q11.2) translocation and detection of the resulting SYT-SSX1 or SYT-SSX2 fusion transcripts are useful diagnostic markers for synovial sarcoma. In this study, we developed a polymerase chain reaction (PCR) assay to amplify SYT-SSX fusion transcripts. The primer sequences were designed to generate small PCR products and to amplify sequences of all known SSX genes as fusion partners for the SYT gene. RNA was obtained from formaldehyde-fixed and paraffin-embedded tissues of 22 immunohistochemically characterized synovial sarcomas, 6 of them cytogenetically confirmed as t(X;18) positive. The SYT-SSX fusion transcripts were detected in 21 of the 22 analyzed cases. The type of the fusion was identified by the specific restriction enzyme digestion pattern as SYT-SSX1 in 13 cases and SYT-SSX2 in 7 cases; in 1 case, the type could not be assigned. None of the cases showed involvement of the SSX3, SSX4, or SSX5 genes, the other members of the SSX gene family. In seven cases, the SYT-SSX1 or SYT-SSX2 fusion transcripts were demonstrated in frozen tissue using a different PCR assay. The PCR products were confirmed as SYT-SSX sequences by sequencing in five randomly selected cases. Fifteen other sarcomas and related tumors were negative for SYT-SSX fusion transcripts. The PCR assay used in this study performs well in formaldehyde-fixed and paraffin-embedded tissue, and it shows a high specificity. This assay can be used as an adjunct test for diagnostically difficult cases or in retrospective studies to refine the diagnosis of synovial sarcoma in archival material.

Adolescent↗
PubMed1997

Synthesis and action on the central nervous system of 3-substituted 2-phenyl-2,3-dihydro-4H-1,3,2-benzoxazaphosphorin-4-one 2-oxide and 2-sulfide derivatives.

The synthesis of 3-substituted 2-phenyl-2,3-dihydro-4H-1,3,2-benzoxazaphosphorin-4-one 2-sulfide derivatives is described. The action of a series 2-oxide (1-6) and 2-sulfide (7-12) derivatives on the central nervous system has been evaluated. Compounds 1-4, 6, 7-10 exhibit neuroleptic activity. Derivatives of sulfide series act as antiserotoninergic drugs.

Animals↗
PubMed1997

Synthesis, structures and biological activity of some 4-amino-3-cinnolinecarboxylic acid derivatives. Part 2.

6,7,8-Substituted 4-amino-3-cinnolinecarboxylic acids 1 were condensed with amines to the corresponding 4-amino-3-cinnolinecarboxamides 7, 8. A variety of pharmacological tests showed a significant CNS activity of some new amides. Decarboxylation of 4-amino-3-cinnolinecarboxylic acids 1 yielded the corresponding 4-aminocinnolines 4 and alkaline hydrolysis of 1 gave 4-oxo-3-cinnolinecarboxylic acids 2. The acids 1 were converted into pyrimido[5,4-c]cinnolines 6 on two ways of synthesis.

Amphetamine↗
PubMed1996

[Chondrosarcoma of the small pelvis imitating an ovarian tumor].

The authors present diagnostic-therapeutic record concerning chondrosarcoma-tumor in 41-year-old women operated on ovary-tumor. They point out the rareness of chondrosarcoma within pelvis, the diagnostic and therapeutic difficulties and relapses into illness after radical remove of tumour without pelvis bones resection.

Adult↗
PubMed1995

Cytogenetic findings in malignant peripheral nerve sheath tumors.

Clonal chromosome aberrations were detected in 8 short-term cultured malignant peripheral nerve sheath tumors (MPNST). Seven had a near-triploid chromosome number and I was in the hyperhaploid-hypodiploid range. No recurrent structural rearrangements were found; the bands most frequently involved (3 tumors) were 7p11, 12p13 and 14q11. The most common numerical changes were loss of a sex chromosome (all tumors) and loss of at least 1 copy of chromosomes 8, 16 and 22 (4 tumors). Pooling our data with those on the 20 previously published MPNST with abnormal karyotypes, we found that the chromosome number has often been in the triploid range (12 tumors), with stem line variation between 34 and 270. All chromosome arms, except 22p and the Y chromosome, were involved in recombinations. The most frequently rearranged bands were 7p22 (6 tumors) and 1p21, 7p11 and 14q11 (5 tumors each). Most numerical and unbalanced structural aberrations have led to loss of genetic material, in particular from Xq26-qter (13 tumors); 11q22-qter and 13p (12 tumors); 9p22-pter, 11p13-pter, 17p and 17q11-21 (11 tumors); 1p22-32 and 1p34-pter (10 tumors) and 6q25-qter and chromosome 16 (9 tumors).

Adolescent↗
PubMed1995

Usefulness of cytogenetic analysis in the diagnosis of undifferentiated synovial sarcoma of the chest wall. A case report.

A case of poorly differentiated spindle cell malignant neoplasm of the chest wall in a 21-year-old man is reported. The results of histopathological and immunohistochemical examinations were not characteristic enough to establish the precise diagnosis. Due to the age of the patient and the location of the lesion and NSE positivity of tumor cells, the possibility of Askin's tumour or malignant peripheral nerve sheath tumour was considered. Cytogenetic analysis revealed a chromosomal translocation t(X;18)(p11;q11), which is known as the specific aberration in synovial sarcoma. Chromosome study seems to be a useful tool for identifying undifferentiated mesenchymal tumours.

Adult↗
PubMed1994

Aberrations of chromosome 22 and polysomy of chromosome 8 as non-random changes in clear cell sarcoma.

Cytogenetic analysis was performed on a primary tumor and a metastatic lesion of a clear cell sarcoma of tendons and aponeuroses (CCS), a rare soft tissue neoplasm of uncertain histopathologic origin. Clonal chromosomal abnormalities resulting in two related clones were found in both tumors. The karyotype was near-triploid with several structural and numerical changes, comprising a der(15;22) (q10;q10). Including the present case, 14 of 15 cases of CCS have had structural or numerical aberrations of chromosome 22 and nine of them (65%) displayed a similar or identical t(12;22)(q13-14;q12-13). Our findings suggest that in the absence of specific t(12;22), other abnormalities of chromosome 22 may be significant. In addition, increased doses of chromosome 8 found in 70% of the tumors strongly suggest a significant role for this chromosome in the development of clear cell sarcoma.

Adult↗
PubMed1994

p53 protein and vimentin in invasive ductal NOS breast carcinoma--relationship with survival and sites of metastases.

p53 protein and vimentin status were available from immunocytochemical studies of 253 formalin-fixed paraffin-embedded invasive ductal not otherwise specified (NOS) carcinomas from patients for whom follow-up data was also on file. For the 127 node-negative patients, multivariate analysis showed a highly significant correlation between p53 and vimentin (P < 0.001), a strong correlation between vimentin and probability of survival to 90 months but only a weak association between p53 and survival to 90 months. p53 also never entered trees of prognostic indicators derived using stepwise regression with Kaplan-Meier statistics for node-negative and node-positive subgroups, while vimentin status dominated the node-negative trunk. In addition, p53 and vimentin status were analysed versus the site of the first distant metastasis for node-negative and node-positive patients. Analysis by p53 status showed no significant effect on visceral metastases. In contrast, vimentin-positive primaries metastasised twice (and in node-negative patients, 3.5 times) as often to lung, liver and brain as did the vimentin-negative primaries. Both p53-positive and vimentin-positive tumours showed a significantly lower tendency to metastasise to the bone than did their negative counterparts.

Adult↗
PubMed1994

Diazepinoquinazolines. Part II. Synthesis and pharmacological activity of some derivatives of 1,4-diazepino[2,1-b]quinazoline.

New derivatives of 1,4-diazepino[2,1-b]quinazoline were obtained. The diazepino quinazoline [IV] was obtained by the condensation of 2,5,6,7-tetrahydro-3-(methylthio)-1-phenyl-1H-1,4-diazepine with 5-chloroantranilic acid. Compounds was preparated in two steps from 2,3,4,5-tetrahydro-1,4-diazepino[2,1-b]quinazolin-7(1H)-one. The derivatives [II-IV], [VII], [VIII] were screened for their psychotropic activity.

Animals↗