Biomedical subjects

B Sipos

Publications and source records attributed to B Sipos.

27 records · Page 2Linked to original sources

PubMed2001

Combretastatin A-4 prodrug inhibits growth of human non-small cell lung cancer in a murine xenotransplant model.

BACKGROUND: Combretastatin A-4 prodrug (CA-4PD) has been identified as a potent antivascular agent in various rodent tumor models. The aim of this study was to investigate the effect of CA-4PD on human non-small cell lung cancer (NSCLC). METHODS: Cytostatic and cytotoxic effects of CA-4PD on selected NSCLC cells, Colo-699 and KNS-62, were studied in vitro. After subcutaneous xenotransplantation the effect of systemically administrated CA-4PD on tumor growth was investigated in vivo. A newly established orthotopic xenotransplant model was employed to estimate prolongation of survival after intrapulmonary tumor induction with secondary metastatic disease. RESULTS: In vitro, CA-4PD displayed a time and dose dependent antiproliferative effect on human lung cancer cells. In vivo, CA-4PD significantly delayed growth of subcutaneously induced lung cancer. This growth delay was translated into a prolongation of survival in the metastasizing orthotopic xenotransplant model. CONCLUSIONS: In vitro CA-4PD inhibits proliferation of NSCLC cells, most likely by disruption of microtubule assembly. In vivo, systemic treatment inhibits growth of subcutaneously xenotransplanted tumors by an antivascular effect. In the case of metastasizing human lung cancer this translated into a prolongation of survival.

Adenocarcinoma↗

PubMed2001

[Successfully operated infraperitoneal hemangiopericytoma infiltrating the left ureter].

Hemangiopericytoma is a very rare tumour originating from the lining cells of small vessels. Despite benign histology it is clinical presentation similar to malignancy. There are only less than hundred cases reported sporadically in the literature. Authors report a case and successful radical removal of an infraperitoneal hemangiopericytoma infiltrating the left ureter. The literature of this strange, rare pathology is also analysed in the article.

Adult↗

PubMed2000

Smad4/DPC4-mediated tumor suppression through suppression of angiogenesis.

Smad4/DPC4 (deleted in pancreatic carcinoma, locus 4) is a tumor suppressor gene lost at high frequency in cancers of the pancreas and other gastrointestinal organs. Smad4 encodes a key intracellular messenger in the transforming growth factor beta (TGF-beta) signaling cascade. TGF-beta is a potent inhibitor of the growth of epithelial cells; thus, it has been assumed that loss of Smad4 during tumor progression relieves this inhibition. Herein, we show that restoration of Smad4 to human pancreatic carcinoma cells suppressed tumor formation in vivo, yet it did not restore sensitivity to TGF-beta. Rather, Smad4 restoration influenced angiogenesis, decreasing expression of vascular endothelial growth factor and increasing expression of thrombospondin-1. In contrast to the parental cell line and to control transfectants that produced rapidly growing tumors in vivo, Smad4 revertants induced small nonprogressive tumors with reduced vascular density. These data define the control of an angiogenic switch as an alternative, previously unknown mechanism of tumor suppression for Smad4 and identify the angiogenic mediators vascular endothelial growth factor and thrombospondin-1 as key target genes.

Animals↗

PubMed1999

Duct changes and K-ras mutations in the disease-free pancreas: analysis of type, age relation and spatial distribution.

Recent molecular studies have suggested that hyperplastic duct lesions of the pancreas are potential precursors of pancreatic ductal carcinoma. This study examines the type, distribution, age-related incidence and K-ras codon 12 mutation rate of duct lesions in the normal pancreas. Postmortem pancreases from 140 patients were screened for the presence of mucinous cell hypertrophy (MHT), ductal papillary hyperplasia (DPH), adenomatoid ductal hyperplasia (ADH), and squamous metaplasia (SQM). Microdissected cell samples were analyzed for K-ras codon 12 mutations by polymerase chain reaction amplification of exon 1 of the K-ras gene, combined with constant denaturing gel electrophoresis, and analyzed by sequencing. Of the 140 specimens 114 showed duct lesions. The lesions were evenly distributed throughout the pancreas. They were more common beyond the age of 40. MHT was present in 68%, DPH in 36%, ADH in 40%, and SQM in 36% of the cases. K-ras mutations were found in 19 samples from 15 out of 79 pancreases (18%), including all types of duct lesions and a variant of ADH with dense stroma. 67% of the K-ras-positive specimens showed the transition GGT to GAT (8) or GTT (5). Hyperplastic/metaplastic duct changes of the pancreas increase with age, but their distribution pattern in the pancreas differs from that of ductal carcinomas.

Adolescent↗

PubMed1999

World Health organization (WHO) and the World Heart Federation (WHF) pathobiological determinants of atherosclerosis in youth study (WHO/WHF PBDAY Study) 1986-1996. Histomorphometry and histochemistry of atherosclerotic lesions in coronary arteries and the aorta in a young population.

BACKGROUND AND AIM: The present work is a chapter in an investigation directed by the World Health Organization on the Pathobiological Determinants of Atherosclerosis In Youth (WHO-PBDAY). Our aim was to study the development of atherosclerotic lesions in a young population. METHODS AND RESULTS: Samples of left anterior descending coronary artery (LDC) and thoracic (TA) and abdominal aorta (AA) from five Collaborating Centres (Budapest/Hungary, Havana/Cuba, Heidelberg/Germany, Mexico City/Mexico, Peradeniya/Sri Lanka) of 214 subjects who died aged 15 and 34 were analysed at the Budapest Reference Centre. Slides stained with haematoxylin-eosin and with stains for extracellular matrix were quantitatively and qualitatively evaluated. Mean intima/media (I/M) ratio and the prevalence of type III-IV lesions (preatheroma; atheroma; calcified and fibrous atheroma) were determined and compared in different risk factor (high blood pressure, smoking) groups. High I/M ratio was found in the LDC and type III-IV lesions were frequently found both in the LDC and in the AA. I/M ratio and the occurrence of type III-IV lesions increased in all arteries by age. Atherosclerotic lesions in men were more severe, particularly in the LDC. Geographic origin had a limited effect on the histologic lesion parameters. Appearance of type III-IV lesions was associated with substantially different extracellular matrix changes. Myoelastic layer formation was found in each artery in both early and type III-IV lesions. Hypertension was associated with higher prevalence of type III-IV lesions in all arteries, in particular, in the TA; smoking showed a significant effect on the AA only. CONCLUSIONS: Atherosclerotic lesions were found in many of these young subjects. The effect of hypertension and smoking on their development suggests that control of risk factors, beginning in early adolescence, could help to prevent cardiovascular diseases.

Adolescent↗

PubMed1998

Pancreatic leiomyosarcoma. Case report with immunohistochemical and flow cytometric studies.

A leiomyosarcoma originating from the pancreas of a 57-year-old man is presented. A 6x5x4 cm tumour was located in the head region, and the patient underwent surgical palliation. Immunohistochemical studies excluded an epithelial origin; a myogenic origin was suggested by strong vimentin and smooth muscle actin positivity. Flow cytometric analysis revealed an aneuploid pattern (DNA index: 1,561). The patient died with widespread metastases 7 month after the operation.

Actins↗

PubMed1998

Atherosclerosis in amputated legs of patients with and without diabetes mellitus.

BACKGROUND: The aim of this study was to compare the histomorphologic appearance of atherosclerosis in amputated legs of diabetic and non-diabetic patients. METHODS: Twenty-eight legs amputated below the knee for chronic ischaemia were studied. Fourteen legs were amputated in patients with diabetes (10 Type II, 4 nonclassified) and 14 in non-diabetics. The mean age of patients at the time of the amputation was 63.3 years in diabetics and 63.9 years in non-diabetics. Samples were taken from the main arteries at the following levels: the midleg, 5 cm above the ankle, 3 cm below the ankle and 10 cm below the ankle. Cross-sections of the arteries were examined with light microscopy and the severity of the occlusive disease determined using morphometric analysis. Medial calcification and chronic inflammation were assessed semiquantitatively. RESULTS: Arteries at 5 cm above the ankle were more severely stenotic in diabetics than in non-diabetics (p<0.05). In both diabetics and non-diabetics the posterior tibial and plantar arteries appeared to be the most stenotic. Medial calcification tended to be more prominent in diabetics than in non-diabetics. Chronic inflammation in the arterial wall occurred at the same degree in diabetics and non-diabetics. In non-diabetics chronic inflammation was more severe in the posterior tibial and plantar arteries than in the anterior tibial and dorsalis pedis arteries (p<0.04). Chronic arterial inflammation correlated with the severity of chronic arterial occlusive disease (p<0.0002). CONCLUSIONS: In diabetics occlusive disease in amputated legs is more severe in arteries above the ankle than in non-diabetics. However, no difference was demonstrated in this series in arteries of the ankle and foot. Diabetics are likely to have more medial calcification in the arteries than non-diabetics. Chronic inflammation in the arterial wall is associated with more severe stenosis.

Amputation, Surgical↗

PubMed1998

Fetal hydropericardium associated with left ventricular diverticulum.

Fetal pericardial effusion usually develops because of fetal heart failure, infections, chromosomal abnormalities, fetal anaemia, intracardiac or extracardiac tumours. There is only one case in the literature of isolated hydropericardium associated with left ventricular diverticulum and here we report another.

Abortion, Induced↗

PubMed1995

[Glandular myxoma of the heart].

Light microscopic, immunohistochemical and ultrastructural studies were performed on a surgically removed left atrial myxoma containing glandular structures. Routine examination showed glandular lumina lined by cylindric epithelium in the characteristic myoxoid stroma, and the glands contained PAS positive mucin. The glandular structures demonstrated significant positivity for wide-spectrum-CK, EMA, and moderate positivity for CEA. Stromal cells were positive for vimentin, FVIII. Ag was present only in surface cells and blood vessels. Ultrastructurally the gland showed characteristics of mucin secreting epithelium. The authors briefly overview the currently existing theories about the histogenesis of myxomas.

Adult↗