Biomedical subjects

B Szende

Publications and source records attributed to B Szende.

At least 37 records · Page 2Linked to original sources

PubMed2001

Formaldehyde promotes and inhibits the proliferation of cultured tumour and endothelial cells.

Formaldehyde was applied in various doses (0.1-10.0 mM) to HT-29 human colon carcinoma and HUV-EC-C human endothelial cell cultures. Cell number, apoptotic and mitotic index as well as proportion of cells in S-phase was investigated by morphological methods and flow cytometry. Ten mM of formaldehyde caused high degree of cell damage and practically eradicated the cell cultures. One mM of formaldehyde enhanced apoptosis and reduced mitosis in both types of cell cultures, in a moderate manner. The low dose (0.1 mM) enhanced cell proliferation and decreased apoptotic activity of the cultured cells, the tumour cells appeared to be more sensitive. The possible role of this dose-dependent effect of formaldehyde in various pathological conditions, such as carcinogenesis and atherogenesis is discussed with emphasis on the eventual interaction between formaldehyde and hydrogen peroxide.

Apoptosis↗

PubMed2001

Wheat germ extract inhibits experimental colon carcinogenesis in F-344 rats.

It has been demonstrated for the first time that a wheat germ extract prevents colonic cancer in laboratory animals. Four-week-old inbred male F-344 rats were used in the study. Colon carcinogenesis has been induced by azoxymethane (AOM). Ten rats served as untreated controls (group 1). For the treatment of the animals in group 2, AOM was dissolved in physiologic saline and the animals were given three subcutaneous injections 1 week apart, 15 mg/kg body weight (b/w) each. In two additional groups Avemar (MSC), a fermented wheat germ extract standardized to 2,6-dimethoxy-p-benzoquinone was administered as a tentative chemo-preventive agent. MSC was dissolved in water and was given by gavage at a dose of 3 g/kg b/w once a day. In group 3, animals started to receive MSC 2 weeks prior to the first injection of AOM daily and continuously thereafter until they were killed 32 weeks later. In group 4 the basal diet and MSC were administered only. At the end of the experiment all the rats were killed by exsanguination, the abdominal large vessels were cut under a light ether anesthesia and a complete autopsy was performed. Percentage of animals developing colon tumors and number of tumors per animals: group 1 - 0 and 0; group 2- 83.0 and 2.3; group 3 - 44.8 (P < 0.001) and 1.3 (P < 0.004), group 4 - 0 and 0. All the tumors were of neoplastic nature also histologically. The numbers of the aberrant crypt foci (ACF) per area (cm(2)) in group 2 were 4.85 while in group 3 the ACF numbers were 2.03 only (P < 0.0001).

Animals↗

PubMed2001

Wheat germ extract decreases glucose uptake and RNA ribose formation but increases fatty acid synthesis in MIA pancreatic adenocarcinoma cells.

The fermented wheat germ extract with standardized benzoquinone composition has potent tumor propagation inhibitory properties. The authors show that this extract induces profound metabolic changes in cultured MIA pancreatic adenocarcinoma cells when the [1,2-13C2]glucose isotope is used as the single tracer with biologic gas chromatography-mass spectrometry. MIA cells treated with 0.1, 1, and 10 mg/mL wheat germ extract showed a dose-dependent decrease in cell glucose consumption. uptake of isotope into ribosomal RNA (2.4%, 9.4%, and 28.0%), and release of 13CO2. Conversely, direct glucose oxidation and ribose recycling in the pentose cycle showed a dose-dependent increase of 1.2%, 20.7%, and 93.4%. The newly synthesized fraction of cell palmitate and the 13C enrichment of acetyl units were also significantly increased with all doses of wheat germ extract. The fermented wheat germ extract controls tumor propagation primarily by regulating glucose carbon redistribution between cell proliferation-related and cell differentiation-related macromolecules. Wheat germ extract treatment is likely associated with the phosphorylation and transcriptional regulation of metabolic enzymes that are involved in glucose carbon redistribution between cell proliferation-related structural and functional macromolecules (RNA, DNA) and the direct oxidative degradation of glucose, which have devastating consequences for the proliferation and survival of pancreatic adenocarcinoma cells in culture.

Adenocarcinoma↗

PubMed2001

Apoptosis in various organs of preterm infants: histopathologic study of lung, kidney, liver, and brain of ventilated infants.

Apoptosis, the well-characterized form of active programmed cell death, is a physiologic phenomenon in embryonal and fetal life in developing organs. Severe hypoxia, which occurs in most preterm infants, also leads to cell death, which may be necrotic or apoptotic. The aim of our study was to examine the incidence of apoptosis in various organs (such as lung, kidney, and brain) of preterm infants who suffered from clinically proven respiratory distress causing infantile respiratory distress syndrome (IRDS), cardiac failure, and periventricular leukomalacia (PVL). Twenty-four autopsy cases were studied histologically to detect the apoptotic ratio, which was performed on the basis of hematoxylin and eosin staining and validated by terminal deoxynucleotidyl transferase-mediated nick end-labeling (TUNEL) reaction. Elevated apoptotic ratio was found in stages II, III, and IV of bronchopulmonary dysplasia (BPD) among alveolar and bronchiolar cells. The apoptotic activity was very low in stage I of BPD. High apoptotic ratio was detected in hypoxic injuries of the central nervous system (CNS) of preterm infants. Features of apoptosis were present in proximal and excreting tubules of the kidney. Significant elevation of apoptotic activity may play a role in the development of BPD, ischemic brain lesions, and renal failure.

Apoptosis↗

PubMed2001

bcl2, p53 and bax in thyroid tumors and their relation to apoptosis.

Twenty five thyroid tumors were investigated by immunohistochemistry for the presence of apoptosis, expression of p53, bax and bcl2. In nine adenomas (average age 40) the rate of p53 positive cells was 5.7%, while it was 13.3% for bax and 41.7% for bcl2 in the tumor cells. In six follicular carcinomas (average age 56) p53 positivity was obtained for 71.1%, while bax and bcl2 positivity constituted 3.4% and 2.5%, respectively. In ten papillary adenocarcinomas (average age 42) p53 was positive in 39.6%, but bax and bcl2 were positive in 3.4% and 3% of the tumor cells, respectively. Almost no signs of spontaneous apoptosis were found in any of the cases. Determination of p53, bax and bcl2 ratio in thyroid tumors may contribute to the differentiation between follicular adenomas and carcinomas.

Adenocarcinoma, Follicular↗

PubMed2000

Development of plasmin and plasma kallikrein selective inhibitors and their effect on M1 (melanoma) and HT29 cell lines.

trans-4-Aminomethylcyclohexanecarbonyl-Tyr(O-Pic)-octylamide (YO-2) inhibited plasmin (PL) selectively, while trans-4-aminomethylcyclohexanecarbonyl-Phe-4-carboxymethylanili de (YO-1) inhibited plasma kallikrein (PK). YO-2 induced apoptosis of M1 (melanoma) cell line and HT29 colon carcinoma cells during 24 h through activation of caspase-3, while YO-1 did not affect either cell line even during 48 h.

Antineoplastic Agents↗

PubMed2000

Dose-dependent effect of resveratrol on proliferation and apoptosis in endothelial and tumor cell cultures.

Experimental data suggest that Resveratrol, a compound found in grapes and other fruits may influence cell proliferation and apoptosis. The aim of our experiments was to study the effect of Resveratrol on tumor cell cultures and an endothelial cell culture in order to examine the effect of various doses of this compound on active cell death and cell proliferation. Human tumor (HT-29, SW-620, HT-1080) and endothelial (HUV-EC-C) cells were treated with various doses of (0.1 to 100.0 microg/ml) Resveratrol in vitro. Cell number, apoptotic and mitotic index was measured 24, 48 and 72 h after treatment. Low doses (0.1-1.0 microg/ml) of Resveratrol enhance cell proliferation, higher doses (10.0-100.0 microg/ml) induce apoptosis and decrease mitotic activity, which is reflected in changes of cell number. Resveratrol influences dose dependently the proliferative and apoptotic activity of human tumor and endothelial cells. The possible role of formaldehyde in the mechanism of action of Resveratrol is discussed.

Antineoplastic Agents, Phytogenic↗

PubMed2000

The somatostatin analogue peptide TT-232 induces apoptosis and chromosome breakage in cultured human lymphocytes.

Somatostatin receptors are supposed to be important in the regulation of apoptosis. In this study, we measured apoptosis occurring spontaneously, or induced by the synthetic somatostatin analogue, the peptide TT-232. We examined isolated human peripheral blood lymphocytes (PBL) from 32 nurses exposed bedside to cytostatic drugs, 12 chronic lymphoid leukaemia (CLL) patients prior to treatment, and 19 unexposed, healthy donors without anamnestic occupational exposure to genotoxic agents. Cells were stimulated by phytohaemagglutinin-P (PHA) and cultured for 69 h with or without 15 microg/ml TT-232, respectively. Cell kinetic parameters and apoptosis were determined by flow cytometry after staining with FITC-labeled anti-BrdU and propidium iodide (PI) and the results on spontaneous and peptide-induced apoptosis were compared with the obtained chromosome aberration frequencies (CA). The peptide TT-232 unexpectedly induced chromosome breakage in addition to apoptosis. The mean spontaneous apoptotic fractions were 6.65+/-0.89%, 6.46+/-0. 53%, and 3.07+/-0.57%, and the mean CA yields in the samples without TT-232 were 1.74+/-0.46%, 2.44+/-0.40%, and 4.50+/-1.05%, for healthy subjects, nurses, and CLL patients, respectively. A total of 15 microg/ml TT-232 treatment in healthy subjects increased the mean CA frequency (10.38+/-1.57%), as well as the apoptotic cell fraction (2.63+/-0.45 times higher than the corresponding untreated sample). In TT-232-treated PBLs of nurses, CA remained unchanged and the mean apoptotic cell fraction showed only a slight increase (1.24+/-0.11 times higher than the untreated). Among CLL patients, TT-232 treatment significantly increased both CA (up to 17.83+/-4.04%) and the ratio of apoptotic cells (21.78+/-11.00 times higher than the untreated). These results demonstrated significant differences in apoptosis sensitivity in controls, nurses and CLL donors, after 15 microg/ml TT-232 treatment. Data also indicate that the induced CA yields in CLL donors with high CA are in correlation with TT-232-induced apoptosis.

Antineoplastic Agents↗

PubMed2000

Apoptotic and non-apoptotic modes of programmed cell death in MCF-7 human breast carcinoma cells.

Apoptosis is a specific mode of programmed cell death (PCD), recognized by characteristic morphological and molecular changes. Here we present evidence for a non-apoptotic type of PCD in human MCF-7 breast carcinoma cells. We used TNF-alpha and tyrphostin AG213 to induce apoptotic and non-apoptotic cell death respectively in vitro. Microscopic and immunohistochemical studies, together with DNA analysis and flow cytometric analysis of p53 and bcl-2 oncogene expression, revealed some novel characteristics of non-apoptotic cell death. We show here for the first time some of the biochemical features of an experimentally induced non-apoptotic PCD and emphasize the distinct biochemical events leading to apoptotic and non-apoptotic PCD.

Apoptosis↗

PubMed2000

Improving diagnostic accuracy of prostate carcinoma by systematic random map-biopsy.

Systematic random rectal ultrasound directed map-biopsy of the prostate was performed in 77 RDE (rectal digital examination) positive and 25 RDE negative cases, if applicable. Hypoechoic areas were found in 30% of RDE positive and in 16% of RDE negative cases. The score for carcinoma in the hypoechoic areas was 6.5% in RDE positive and 0% in RDE negative cases, whereas systematic map biopsy detected 62% carcinomas in RDE positive, and 16% carcinomas in RDE negative patients. The probability of positive diagnosis of prostate carcinoma increased in parallel with the number of biopsy samples/case. The importance of systematic map biopsy is emphasized.

Aged↗

PubMed2000

Accuracy of clinical diagnosis of lung cancer in Budapest in an institute specializing in chest diseases.

Among 250 consecutive autopsies (170 males and 80 females) performed at the Institute of Pulmonology in Budapest in 1996/7, there were 132 deaths in which cancer of the lung/bronchus was deemed to be the underlying cause of death. At autopsy, six cases previously thought to be dying from lung cancer were found to have died from other diseases (false positive rate = 5%). Twelve lung cancer deaths were also found to have been missed, a false negative rate of 9%, which was similar for adenocarcinoma, squamous carcinoma, and small cell carcinoma cases. Our findings confirmed the expectation expressed earlier that death certification of lung cancer would be more accurate in an institute specializing in chest diseases, to which patients had to be fit enough to be transferred, than in two general hospitals in Budapest. Nevertheless, since most cases certified as dying from lung cancer die without the benefits available in the specialized institute, the estimated false negative and positive rates for lung cancer death certification in Hungary remain high, at an estimated 56% and 30%, respectively. The much lower autopsy rates in most other countries than in Hungary points to there being considerable inaccuracy in lung cancer mortality rates internationally.

Adult↗

PubMed2000

Antagonists of growth hormone-releasing hormone (GH-RH) inhibit IGF-II production and growth of HT-29 human colon cancers.

Insulin-like growth factors (IGFs) I and II are implicated in progression of various tumours including colorectal carcinomas. To interfere with the production of IGFs, we treated male nude mice bearing xenografts of HT-29 human colon cancer with various potent growth hormone-releasing hormone (GH-RH) antagonists. Twice daily injections of antagonist MZ-4-71, 10 microg intraperitoneally or 5 microg subcutaneously (s.c.) resulted in a significant 43-45% inhibition of tumour growth. Longer acting GH-RH antagonists, MZ-5-156 and JV-1-36 given once daily at doses of 20 microg s.c. produced a 43-58% decrease in volume and weight of cancers. Histological analyses of HT-29 cancers demonstrated that both a decreased cell proliferation and an increased apoptosis contributed to tumour inhibition. GH-RH antagonists did not change serum IGF-I or IGF-II levels, but significantly decreased IGF-II concentration and reduced mRNA expression for IGF-II in tumours. In vitro studies showed that HT-29 cells produced and secreted IGF-II into the medium, and addition of MZ-5-156 dose-dependently decreased IGF-II production by about 40% as well as proliferation of HT-29 cells. Our studies demonstrate that GH-RH antagonists inhibit growth of HT-29 human colon cancers in vivo and in vitro. The effect of GH-RH antagonists may be mediated through a reduced production and secretion of IGF-II by cancer cells.

Animals↗

PubMed2000

Spontaneous apoptosis and retinoic acid receptor incidence in neuroblastomas and peripheral neuroectodermal tumors.

Twelve cases of neuroblastoma (NB) (7 boys and 5 girls) and 4 cases of primitive peripheral neuroectodermal tumor (PNET) (3 boys and 1 girl) were investigated for the presence of apoptosis and retinoic acid receptor (RAR) by immunhistochemical method. The apoptotic index in NB was zero or 1% in 8 children and relatively low (2-4.8%) in the other 4 cases, while it was higher (4.1-10.5%) in PNET. The RAR index determined by immunoperoxidase reaction in NB was zero or 3% in 5 cases and 9-34% in 7 children. RAR index in PNET was 16-68% in all the 4 cases. Good correlation (r = .47 according to Pearson-Bravis) was found between the number of RAR and spontaneous apoptosis. These results suggest that the RAR index in untreated NB and PNET shows great individual variation since its determination is necessary for the evaluation of the efficacy of retinoic acid treatment.

Apoptosis↗

PubMed2000

Follow-up of prostate carcinoma patients treated with total androgen blockade by repeated map-biopsy.

A prospective study was carried out on ten patients with prostate cancer. The TNM stage, Gleason's grade, general clinical status and, serum PSA level were all registered by the time of diagnosis. Total androgen blockade (TAB) was performed. Serum PSA control and general clinical examination re-biopsy was performed on average 107 days after the start of the therapy. The pre- and post treatment histology included HE and Tunel reaction to show apoptotic cells, as well as p53, bcl2 and Ki67 immunostaining. Clinical improvement of the disease, manifested by regression or by steady state was observed in all ten patients. An increase of apoptotic index, and a decrease of mitotic index was detected in most cases. The serum PSA level decreased in all patients. Ki67, bcl2 and mutant p53 were strongly expressed in tumor cells of patients in whom Gleason's grade was 7 or higher and decreased markedly in all cases upon therapy. Data obtained by repeated biopsy in the course of TAB therapy are indicators of the effectiveness of TAB, like changes in serum PSA, and may be considered as predictive factors.

Aged↗

PubMed2000

Apoptotic and antiapoptotic effect of (-)deprenyl and (-)-desmethyl-deprenyl on human cell lines.

The antiapoptotic effect of (-) deprenyl on human phaeochromocytoma cells after serum deprivation has been reported by earlier. Two melanoma (M-1 and HT-2058) cell lines were used in our experiments. Serum deprivation for five days resulted in excessive number of apoptosis in the cell cultures. Very low doses of (-)-deprenyl (10(-7)-10(-13) mol) caused an approximately 2 days delay in the onset of apoptosis. At the same time, +deprenyl was ineffective. In further experiments (-)-deprenyl and (-)desmethyl-deprenyl was administered in higher doses (10(-2), 10(-3) and 10(-4) mol) to A-2058 melanoma and HT-1080 fibrosarcoma cells in culture. In these experiments no serum deprivation was applied and the treatment was started 24 hours after plating. Total eradication of the A-2058 cells was caused by 10(-2) mol (-)-deprenyl and (-)-desmethyl-deprenyl. The type of cell death appeared to be apoptosis. Sixty percent apoptotic ratio was seen 24 hours and 72 hours after 10(-3) mol (-)-desmethyl-deprenyl treteatment. The same dose of (-)-deprenyl caused 50% apoptosis an 72 h. Only (-)-desmethyl-deprenyl induced apoptosis (20%) at 24 hours, in the dose of 10(-4) mol. Interestingly (-)-deprenyl treatment resulted in 60% apoptosis.

Amphetamines↗

PubMed1999

Novel lipoamino acid- and liposaccharide-based system for peptide delivery: application for oral administration of tumor-selective somatostatin analogues.

Lipoamino acid and liposaccharide conjugates of somatostatin analogue TT-232 were synthesized to modify the physicochemical properties of the parent peptide. The relative position, the number, and the nature of the lipid and/or saccharide moieties were varied. Experiments in vitro clearly showed that many compounds modified at the N- and/or C-terminus with lipid or sugar moieties retained the biological activity of the parent compound. An interesting construct was synthesized containing lipid and sugar units at opposite ends of the somatostatin analogue, so that the entire molecule could be considered as an amphipathic surfactant.

Administration, Oral↗

PubMed1999

[Practice of fetal pathological examination].

Authors report on the practice and most important genetic questions of fetopathological examinations. A so called genetic-morphologic approach is suggested. The observer needs special knowledge to recognize major and minor signs of defects in fetuses in the second, or sometimes even in the first trimester. Spontaneous abortions in the first trimester are caused mainly by chromosome aberrations. In the second trimester the main causes of spontaneous abortions are maternal in origin or secondary to intrauterine infection. Medical legal aspects are also reviewed. For proper documentation a photo or X-ray must be taken. Cytogenetic and molecular genetic methods are also very important tools, therefore examination must be performed before fixation. For the first time in Hungary fetal biometric data are presented with correlation between gestational age and different organ weights. Our aim is to promote better understand of fetal malformations and disorders.

Abortion, Induced↗

PubMed1999

Effect of MSC on the immune response of mice.

The supposed immunostimulatory actions of MSC, a new fermented wheat germ extract standardized to its benzoquinone composition (trade name: AVEMAR) were studied examining blastic transformation of peripheral blood lymphocytes of mice treated with MSC. It was found that MSC significantly increased the degree of blastic transformation caused by Concanavalin A. Using the B10LP to C57Bl skin graft system, MSC (0.03 and 3.0 g kg(-1) applied orally) acted in favour of restoring the immune function. On the other hand, 2,6-dimethoxy-p-benzoquinone (DMBQ), applied in equivalent doses (0.012 and 1.2 mg kg(-l)), did not shorten the rejection time of skin grafts. The immune restoring effect, as well as the blastic transformation enhancing potential of MSC may be exploited in various cases of decreased immune response.

Adjuvants, Immunologic↗