Biomedical subjects

Pavel Dundr

Publications and source records attributed to Pavel Dundr.

13 recordsLinked to original sources

PubMed2006

Establishment, growth and in vivo differentiation of a new clonal human cell line, EM-G3, derived from breast cancer progenitors.

A new clonal cell line, EM-G3, was derived from a primary lesion of human infiltrating ductal breast carcinoma. The line consisted of cuboidal cells with occasional appearance of more differentiated branched cells apparently involved in cell-to-cell communication. The EM-G3 cells, population doubling time 34 h, are dependent on the epidermal growth factor. Multicolor fluorescence in situ hybridization (mFISH) analysis demonstrated a stable diploid genome with several genetic changes. Immunocytochemical analysis of EM-G3 in vitro revealed positivity for keratins (K) K5, K14, K18, nuclear protein p63, epithelial membrane antigen (EMA) and other proteins indicative of a pattern of mammary epithelium bipotent progenitors. Detection of integrins alpha-6, beta-1, and protein CD44 by cDNA array also pointed to the character of basal/stem cells. In contrast, dominant cells in the human original tumor showed the luminal character (K18+, K19+, K5-, K14-, and p63-). However, cells with the immunocytochemical profile similar to that of cultured EM-G3 cells were found in minor clusters in the patient's tumor sections. The EM-G3 cells formed limited tumors in nu/nu mice. The cells in mouse tumors were organized in primitive ductal-like structures consisting of 1-3 large central luminal-like cells (EMA+) surrounded by peripheral myoepithelial-like cells (p63+/EMA-). The large central cells gradually disintegrated, forming a pseudolumen. Apparently, EM-G3 cells are able to partially differentiate in vivo as well as in vitro. Our results indicate that EM-G3 cells were derived from a premalignant population of common progenitors of luminal and myoepithelial cells that were immortalized in an early stage of tumorigenesis.

Animals↗

PubMed2006

Pathological findings of uterine leiomyomas and adenomyosis following uterine artery embolization.

Uterine artery embolization (UAE) is an effective and accepted treatment option for symptomatic uterine leiomyoma. Between 2000 and 2005, 91 women were treated using this method, and were prospectively followed at our institution. Twenty of them subsequently underwent surgery. One of these patients was subjected to four surgical procedures. We describe the pathological findings of 23 surgical specimens obtained from these 20 patients. The embolic material used consisted of tris-acryl gelatin microspheres (TGMS) in 15 patients (18 surgical specimens), polyvinyl alcohol particles (PVA) in three patients, and a combination of PVA and TGMS in two patients. Histologically, of the 23 specimens examined, 20 were diagnosed as leiomyomas, and three as adenomyosis. Particles used for embolization were found in all but three specimens. Necrosis was present in 15 of 20 leiomyoma specimens. Hyaline necrosis was found in 12 specimens, coagulative necrosis in one case, and a combination of hyaline and coagulative or suppurative necrosis in two cases. The foci of adenomyosis remained unaltered.

Adult↗

PubMed2006

Up-regulation of p21WAF1 expression is mediated by Sp1/Sp3 transcription factors in TGFbeta1-arrested malignant B cells.

BACKGROUND: TGFbeta1 has a profound effect on the growth of various mammalian cell types, including B lymphocytes. The inhibitory action of TGFbeta1 is mediated by deactivation of the cell cycle machinery. Several feedback-sensitive pathways determine whether the cells are stopped in G1 phase or allowed to leave G1 phase and enter S phase. Cell cycle-associated molecules, e.g. cyclin-dependent kinase inhibitors (CKIs), may become targets for the inhibitory signaling pathways induced by TGFbeta1. MATERIAL/METHODS: Our experimental DoHH2 cell line model was derived from a patient with malignant non-Hodgkin's lymphoma of follicular origin. The effect of TGFbeta1 on cell cycle progression was studied by flow cytometry. We examined the effect of TGFbeta1 on the expression of p21WAF1 by immunoblotting and RT-PCR. The binding activity of transcription factors to the p21 gene promoter was determined by gel mobility shift assay (GMSA). RESULTS: Our results showed that TGFbeta1 treatment increased the number of cells arrested in G0/G1 phase compared with untreated control cells. Moreover, we found that p21WAF1 expression was significantly up-regulated on the protein level after TGFbeta1 treatment. Similarly to the protein level, the expression of p21 mRNA was increased in TGFbeta1-treated cells. We further examined the binding activity of the Sp family of transcription factors to examine their role in p21WAF1 up-regulation. CONCLUSIONS: The results indicated that p21WAF1 over-expression in TGFbeta1-arrested malignant B cells is mediated by binding of Sp1/Sp3 transcription factors to the (-92/-71), (-77/-58), and (-65/-45) elements of the promoter region of the p21 gene.

B-Lymphocytes↗

PubMed2006

Intraneural perineurioma of the oral mucosa.

A 16-year-old boy presented with an intraneural perineurioma arising from a small nerve in the buccal mucosa. Histologically, the tumour comprised a tortuous proliferation of spindle cells arranged like an onion bulb. To our knowledge this is the third example of an intraneural perineurioma that did not present in a major nerve.

Adolescent↗

PubMed2006

Adrenocortical adenoma with rhabdoid features.

We report a case of an aldosterone producing adrenocortical adenoma with rhabdoid features in a 16-year-old girl. Grossly, the tumor measured 30 mm in diameter and weighed 24 g. Histologically, the tumor was composed of approximately equal parts of tumor cells with rhabdoid features arranged in a solid and trabecular pattern and cells characterized by compact eosinophilic cytoplasm, solid growth with focal necroses, and increased mitotic activity. The lipid-rich tumor cells with ample clear vacuolized cytoplasm represent a minor component. Immunohistochemically, all the tumor cells showed the same results and were positive for vimentin, synaptophysin, Melan A, and alpha-inhibin. Cytokeratin CAM 5.2 was positive only focally. Chromogranin A, actin, alpha-actin, S100 protein, EMA, and cytokeratin AE1/AE3 were negative. Rhabdoid features have been described in many tumors of variable histogenesis; however, to the best of our knowledge, the presence of rhabdoid phenotype has never been described in either adrenocortical adenoma or carcinoma.

Adolescent↗

PubMed2005

Novel somatic mutations in the BRCA1 gene in sporadic breast tumors.

Germline mutations in two major susceptibility genes BRCA1 and BRCA2 contribute to the majority of inherited breast and ovarian cancers. Besides the germline mutation, tumor progression depends on the loss of a wild-type allele. Allelic losses in the BRCA1 and BRCA2 loci have also been detected in a high proportion of sporadic breast tumors, suggesting the role of these genes in the development of non-inherited breast cancer. Forty unselected breast tumors were analyzed for the loss of heterozygosity (LOH) at BRCA1 and BRCA2 regions and tumors with allelic deletions were screened for the presence of acquired genetic alterations in respective genes. 21.1% of 38 informative tumor samples carried LOH at the BRCA1 locus whereas 33.3% of 39 informative samples showed LOH at the BRCA2 locus. Pathogenic truncating mutations in the BRCA1 gene were found in two tumor samples with allelic losses, whereas no mutations were identified in the BRCA2 gene. Mutations were not detected in non-tumor samples from the same individuals, which indicated that the BRCA1 allele was inactivated by somatic mutations in tumor tissue. The c.1116G>A (1235G>A) nonsense mutation (p.W372X) belongs to the genetic abnormalities detected infrequently in hereditary tumors; the c.3862delG (3981delG) frameshift mutation (p.E1288fsX1306) is a novel gene alteration. The occurrence of inactivating somatic mutations in sporadic breast tumors suggested the role of the BRCA1 gene in tumorigenesis in at least a minor group of patients with non-familial breast cancer.

Adult↗

PubMed2005

Molecular diagnosis of synovial sarcoma: RT-PCR detection of SYT-SSX1/2 fusion transcripts in paraffin-embedded tissue.

BACKGROUND: Synovial sarcomas comprise up to 10 percent of malignant soft tissue tumors, and most are characterized by the chromosomal translocation t(X;18) (pl 1.2;q11.2), which results in the expression of SYT-SSX fusion transcripts. These tumors include two major histological subtypes, biphasic and monophasic. Diagnosing biphasic synovial sarcomas does not usually pose a problem, whereas the monophasic spindle-cell form can be difficult to distinguish from other spindle-cell neoplasms using histological and immunohistochemical profiles only. MATERIAL/METHODS: We investigated the presence of SYT-SSX1/2 chimeric RNA in tumors from 7 patients. We applied amplification of the specific fusion transcripts by reverse transcriptase-polymerase chain reaction (RT-PCR) in fresh, frozen tumors. We also developed a method useful for RT-PCR SYT-SSX fusion transcript detection in formalin-fixed, paraffin-embedded tissue. RESULTS: We found that both histological subtypes of synovial sarcoma were SYT-SSX positive. Moreover, we observed a correlation between histological subtype and type of SYT-SSX fusion transcript. Biphasic synovial sarcoma expressed the SYT-SSX1 fusion transcript, whereas the monophasic subtype expressed the SYT-SSX2 fusion transcript. CONCLUSIONS: The detection of SYT-SSX1/2 fusion transcripts by RT-PCR is a valuable diagnostic marker of synovial sarcoma which can be used for the reclassification of cases whose diagnosis is difficult by routine methods.

Adult↗

PubMed2004

Granular cell basal cell carcinoma.

A 69-year-old woman presented with a 2-year history of a slowly growing tumour on the nose. The clinical diagnosis was basal cell carcinoma (BCC) and a complete excision was performed. Histologically, the tumour had the general features of a BCC but with sheets and nests of cells with granular cytoplasmic changes in the centre of the lesion. A pathological diagnosis of granular cell BCC was made. On immunohistochemical examination, the tumour cells were Ber-EP4, cytokeratin AE1/AE3 and cytokeratin CAM 5.2 positive but S100 protein negative. Only the granular cells were CD68 antigen (monoclonal antibody KP1) positive.

Adult↗

PubMed2003

Pseudoglandular myxoid adenoma of the adrenal gland.

Myxoid tumors of the adrenal cortex are rare. To the best of our knowledge, only 17 cases have been reported to date, including 10 carcinomas and 7 adenomas. The myxoid areas of these tumors are often evident grossly, and their extent is variable. We report on a case of a myxoid adenoma of the right adrenal gland in a 45-year-old male with a prominent pseudoglandular arrangement in more than 90% of the tumor mass, and with a minor component represented by anastomosing cords of tumor cells floating in pools of myxoid material. In addition, after extensive examination, we found foci of typical adrenocortical adenoma. Grossly, the tumor was yellowish without discernable gelatinous changes. Most of the tumor cells had a moderate amount of clear vacuolated cytoplasm and contained numerous oil-red-O-positive lipid droplets. Extracellularly, in the lumens of pseudoglands and on the background, we noticed myxoid material that stained positively with Alcian blue (pH 2.5) and weakly positively with mucicarmine and the PAS method. Immunohistochemical examination showed positivity of the tumor cells for vimentin and cytokeratin CAM5.2. Synaptophysin was weakly positive only focally. Cytokeratin AE1/AE3, EMA, and CEA were negative.

Adrenal Cortex Neoplasms↗

PubMed2003

Large cell neuroendocrine carcinoma of the urinary bladder with lymphoepithelioma-like features.

The group of undifferentiated carcinomas of the urinary bladder encompasses small cell undifferentiated carcinoma, giant cell carcinoma, lymphoepithelioma-like carcinoma (LELC), and large cell neuroendocrine carcinoma (LCNEC). These tumors are either pure or can be associated with other components, such as transitional cell carcinoma, squamous cell carcinoma, and adenocarcinoma. We report a case of LCNEC of the urinary bladder in a 54-year-old woman. Histologically, the tumor showed features of LELC; immunohistochemically, the tumor cells reacted to chromogranin A, NSE, and synaptophysin. In addition to these neuroendocrine markers, tumor cells were positive for cytokeratin CAM 5.2 and AE1/AE3, and there was focal positivity for vimentin. In situ hybridization for the detection of Epstein-Barr virus was negative. Despite radical cystourethrectomy and six courses of chemotherapy, the patient developed metastases invading the left inguinal lymph nodes 11 months postoperatively. Currently, 16 months postoperatively, the patient has developed metastases spreading into the lymph nodes of the right ischiorectal fossa; therefore, she is receiving a new cyclus of chemotherapy. There are only three previously reported cases of LCNEC of the urinary bladder, and the significance of neuroendocrine differentiation in non-small cell carcinomas at this location remains to be established. However, LELC appears to be a separate clinicopathological entity with sensitivity to chemotherapy and a relatively favorable prognosis. The differentiation between LELC and LCNEC with prominent inflammatory reaction could be of therapeutic relevance. However, in our case, this was possible using immunohistochemistry only.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2003

Pigmented composite paraganglioma-ganglioneuroma of the urinary bladder.

We report a case of a pigmented composite paraganglioma-ganglioneuroma of the urinary bladder in a 70-year-old female. Grossly, the tumor measured 6.5 cm in diameter and had arisen from the base of the urinary bladder. Histologically, the tumor was composed of approximately equal components of paraganglioma and ganglioneuroma, which were partly separated and partly mixed, and intermingled with each other. There were foci of ample dark brown pigmentation in the cytoplasm of chromaffin paraganglioma cells. The pigment was Masson-Fontana-positive and had been bleached by hydrogen peroxide (H2O2). Electron microscopy showed large, abundant, pleomorphic electron-dense granules consistent with neuromelanin. In addition, there were numerous electron-dense neurosecretory-type granules. Neuromelanin, melanin or lipofuscin are occasionally observed in paragangliomas, although the occurrence of these pigments has never been described in a composite tumor originating from either adrenal medulla or extraadrenal paraganglia. To the best of our knowledge, our report represents the first case of pigmented composite paraganglioma-ganglioneuroma and expands the morphological spectrum of these unusual tumors.

Aged↗

PubMedDate not supplied

Fetal anemia, thrombocytopenia, dilated umbilical vein, and cardiomegaly due to a voluminous placental chorioangioma. A case report.

We report a case of voluminous placental chorioangioma diagnosed by ultrasound and color Doppler imaging during the 20th week of pregnancy. The size of the tumor was enlarging progressively (up to 10 cm in the 32nd week), and during this time the signs of fetal intrauterine volume overload and blood cell consumption, such as cardiomegaly, umbilical vein dilation, hydramnios, anemia, and thrombocytopenia, were observed. In the 32nd week of pregnancy, the signs of uteroplacental insufficiency and fetal hypoxia appeared; therefore, the pregnancy was terminated by cesarean section, and a female infant weighing 1,870 g was delivered. She was discharged, fully recovered, after 48 days. Histopathological examination of the placental tumor showed a benign, vascular-type chorioangioma.

Adult↗

PubMedDate not supplied

Gallbladder carcinoma cells in cerebrospinal fluid as the first manifestation of a tumor. A case report.

BACKGROUND: Meningeal carcinomatosis (MC) rarely occurs as the first evidence of a tumor. In such cases cytology of the cerebrospinal fluid is crucial to the diagnosis. The most frequent primary MCs are lung and breast cancers. MC from a gallbladder carcinoma is uncommon. CASE: A 58-year-old woman presented with paroxysmal headaches, seizures and coma. Analysis of the cerebrospinal fluid revealed carcinoma cells and a low protein concentration. Only postmortem examination discovered gallbladder adenocarcinoma to be the source of the tumor cells. CONCLUSION: A case with the onset of MC secondary to rare mucinous adenocarcinoma of the gallbladder is presented. Cytology of the cerebrospinal fluid was the only examination that uncovered malignancy. Nine similar cases were found in the literature. Low cerebrospinal fluid protein seems to be of diagnostic value.

Adenocarcinoma↗