Biomedical subjects

I Kiss

Publications and source records attributed to I Kiss.

266 records · Page 15Linked to original sources

PubMedDate not supplied

Copy number of cancer genes predict tumor grade and survival of pancreatic cancer patients.

Pancreatic cancer is on the increase. While means of early diagnosis are being sought, it continues to present late. Prognostication is based on patient and tumor characteristics, including expression or mutation of cancer-related genes. Few studies have examined the impact of the amplification of these genes on the outcome of pancreatic cancer. We have now used a non-radioisotopic slot-blot technique to relate gene copy numbers of p53, c-myc and K-ras to tumor grade and survival. Outcomes were corrected for patient characteristics, tumor location and TNM staging. The Kaplan-Meier test for likelihood of survival showed that increase in copy number of the two oncogenes and loss of p53 were associated with non-significant reduction in survival. When these variations in cancer gene copy numbers were, however, examined by logistic regression analysis in the context of patient and tumor characteristics, survival was negatively related to K-ras amplification (p = 0.0291). Tumor grade, but not survival was positively related to loss of p53 gene copy (p = 0.0131) as well as c-myc amplification (p = 0.0248). Thus using a simple non-radioisotopic technique for the detection of cancer gene copy number in association with patients and disease characteristics, we could predict survival on the one hand and tumor behavior on the other. Such information could be used to plan initial and follow-up therapy.

Adult↗

PubMedDate not supplied

Changes in expression of onco- and suppressor genes in peripheral leukocytes--as potential biomarkers of chemical carcinogenesis.

An animal model was developed to investigate the expression of two oncogenes (c-myc, Ha-ras) and a suppressor gene (p53) as early markers of the effects of carcinogenic exposure and/or tumourigenesis. Inbred Long-Evans rats were treated with 7,12-dimethylbenz(a)anthracene and the transient/permanent gene expressions were measured after 24 and 48 hours by dot blotting in potential target tissues (lung, liver, lymph nodes, kidneys, spleen) and in peripheral blood leukocytes. The aim of the study was to test blood leukocytes, as surrogate tissue, showed similar expression patterns of the selected genes following carcinogenic exposure. c-myc did not prove to be an applicable early biomarker due to the lack of or low level of its expression. However, remarkable of early elevations were detected in the expression signals of Ha-ras and p53.

9,10-Dimethyl-1,2-benzanthracene↗

PubMedDate not supplied

Long-term effects of 1-nitropyrene on oncogene and tumor suppressor gene expression.

Late changes in the expression of oncogenes and tumor suppressor genes following carcinogenic exposure were examined in lung, liver and kidney. 1-Nitropyrene (1-NP), which is a high-risk exposure factor in urban and industrial zones, was used as a carcinogenic agent. c-myc, Ha-ras and p53 gene expression was investigated after administration of a single dose of 1-NP to sensitive CBA/Ca mice in lung, liver and kidney for one year. One week after a single dose 1-NP administration, the expression of p53 was elevated in the liver, but, decreased in the lung and kidney. There was no increase in the expression of c-myc or Ha-ras genes at that time. One month after the administration of the 1-NP, the expression of p53 was increased in the kidney while the expression of Ha-ras and p53 was elevated in the liver. There was no significant difference in gene expression between the treated and control animal groups at any of the investigated periods except for the above-mentioned organs and at the end point of the investigation. According to the literature, 1-NP and its metabolites remain at high concentrations in the kidney, liver and lung. The concentration of the carcinogenic agent and the expression of the studied genes did not seem to correlate with each other in this experiment.

Animals↗

PubMedDate not supplied

Early effects of different cytostatic protocols for head and neck cancer on oncogene activation in animal experiments.

In vivo investigations on oncogenes and onco-suppressor genes may provide new findings on the potential carcinogenic effects of various cytostatic protocols inducing secondary tumours of the head and neck. Further surgeries are often necessary due to regional recurrence after the Cisplatin-supplemented BVM (Bleomycin, Vincristine, Methotrexate) protocol in the treatment of human head and neck tumours. Our earlier studies have illustrated the carcinogenic and mutagenic potential of Cisplatin. The effect of Cisplatin on the alteration of different onco- and suppressor genes has also been proven. Our present study aimed at investigating the early effects of the BVM and the CFu (Cisplatin, 5-Fluorouracil) protocols on early oncogene and tumour suppressor gene expressions in mice. Body weight equivalent amounts of cytostatics were administered intraperitoneally to 6- to 8-week-old, inbred, female CBA/Ca mice. Twenty-four, 48 and 72 hours after the treatment, RNA was isolated from the target organs and the quantitative expression of c-myc, Ha-ras and p53 genes were examined. The protocols caused detectable changes. A "short-term" in vivo test, the 24-hour examination of gene expression, is suitable for detecting early effects of carcinogen exposure. The alterations of gene expression, caused by the Cisplatin-containing protocol, draw attention to the probable role of Cisplatin in the development of regional recurrence and to the possibility of prevention.

Animals↗

PubMedDate not supplied

[Effect of chronic vitamin D deficiency on joint cartilage].

The effect of six-months rachitic diet on the articular cartilage of 12 white Whistar male rats has been studied using light, polarisation, and electronmicroscopes. On the basis of our observations radical changes could be noticed. The intracellular accumulation of glycogen and lipid and the necrosis of cells in the proof/inner/zone indicate the modifications of the cell's structure. The effect of permanent diet on the ground substance of articular cartilage was identified by irregular collagen fibers, and quantitative and qualitative changes of GAGs. On the basis of several author's argumentations it can be supposed that different illness/insufficiency of liver and kidney, and disturbance of resorption in human/can induce similar changes of articular cartilage which was produced by a long term rachitic diet. The cytological picture after long lasting rachitic diet is comparable with the arthrosis.

Animals↗

PubMedDate not supplied

Carcinogenic effects of cytostatic protocols in CBA/Ca mice.

An in vivo mouse model was developed in order to study the characteristics of secondary tumor induction by cytostatic drug combinations used in human anticancer treatment. In this model we have proved the carcino-leukemogenic effects of widely used chemotherapeutical drug combinations (CHOP, COPP, COPBLAM, VAM). The carcinogenic hazards of cyclophosphamide and other alkylating drugs could also be demonstrated in our model.

Animals↗

PubMedDate not supplied

Effect of different cytostatic protocols on oncogene expression in CBA/Ca mice.

In vivo investigations on oncogene action may provide new findings on the toxicology of potential carcinogens. In this study we investigated the early effects of different cytostatic protocols on early oncogene expression in CBA/Ca mice. Most of the examined protocols showed detectable early changes, especially those containing cyclophosphamide. The most frequently involved oncogenes were N-ras, c-myc, and c-myb.

Animals↗

PubMedDate not supplied

Early effects of cyclosporin A on in vivo oncogene expression.

Cyclosporine is a widely used immunosuppressant drug, but development of secondary malignancies has been observed after Cyclosporine containing treatments. In our study we investigated the early effect of Cyclosporin A on oncogene expression. 6, 12, 18 and 24 hours after 80 mg/bwkg Cydosporin A treatment, RNA was isolated from different organs, slot blotted onto Hybond N+ membrane and hybridized with chemiluminescently labelled oncogene probes. As a positive control, rehybridisation with beta-actin probe was used. X-ray films were exposed for 15 minutes, developed, evaluated with densitometer, and the results were expressed as a ratio to the positive control. There was no effect of Cyclosporine A on the expression of c-sis and il-2 receptor genes. The expression of N-ras, c-myc, c-ptc/ret and c-myb oncogenes was elevated in the thymus, lymph nodes, spleen and liver, either transitionally or continuously. We could not detect any elevated gene expressions in the kidney, lung and bone marrow.

Animals↗

PubMedDate not supplied

In vivo effects of cyclophosphamide on oncogene and suppressor gene expression in a "follow up" study.

Cyclophosphamide is a chemotherapeutical drug, with proved carcinogenic side effects. Our previous experiments showed its effect on the expression of certain oncogenes and tumor suppressor genes. In order to further explore the effects of cyclophosphamide at the gene level an in vivo mouse model was developed. We compared the effects of cyclophosphamide with that of cyclosporine, which is a non genotoxic human carcinogenic chemical. After different time periods of intraperitoneal cyclophosphamide or cyclosporine injection, RNA was isolated from whole organs of experimental animals, and expression of onco/suppressor genes was determined by slot blot hybridisation. In our model we have proved that gene expression changes caused by cyclophosphamide can be detected even six months after treatment without tumor development. Our results support the hypothesis that gene expression investigations could be useful biomarkers in monitoring the effects of environmental carcinogenic compounds.

Animals↗

PubMedDate not supplied

In vivo effects of COPP protocol on onco- and suppressor gene expression in a 'follow up study'.

In vivo investigation of onco or suppressor genes may provide new information concerning chemical carcinogenesis. In earlier studies we illustrated the carcinogenic potential of COPP chemotherapeutical protocol in "long term" experiments. Elevated expression of oncogenes was shown as soon as 24 hours after treatment in CBA/Ca inbred mice, in "short term" experiments. Now we present the results of the follow-up study dealing with the carcinogenic effect of COPP. The genes most frequently involved were N-ras and p53, with the thymus being the target organ of COPP.

Animals↗

PubMedDate not supplied

Effect of 7,12-dimethylbenz(a)anthracene on onco/suppressor gene action in vivo: a short-term experiment.

Dimethylbenz[a]anthracene is a pluripotent carcinogenic chemical, which acts as an initiator by causing point mutations in certain oncogenes and tumor suppressor genes. Changes in their expression may be another possible area of investigation the carcinogenic effect of DMBA. Elevated expression of oncogenes was previously has been shown after treatment with carcinogenic compounds. In the present study, expression of c-myc, c-Ha-ras and p53 24 hours after a single dose treatment of DMBA in the spleen and in the liver of Long-Evans rats was investigated. Control animals were injected with the solvent corn oil only. We could not find any significant change on the transcriptional level of the investigated oncogenes in the liver. In the spleen, the overexpression of Ha-ras was 2-fold and c-myc was 3-fold higher in the DMBA-treated rats than in the corresponding control group. Since DMBA is a typical environmental carcinogen, the results of animal experiments may serve as a basis for application of gene expression investigations as a screening method in humans.

9,10-Dimethyl-1,2-benzanthracene↗

PubMedDate not supplied

Effect of ABVD therapeutic protocol on oncogene and tumor suppressor gene expression in CBA/Ca mice.

The in vivo investigation of onco/suppressor gene effects may provide new information on chemical-environmental carcinogenesis. We previously described the elevation of onco/suppressor gene expression due to CHOP and COPP chemotherapeutical protocols in a CBA/Ca mouse model. Below we describe the results of the onco/suppressor gene expression studies after treatment with ABVD, a non-cyclophosphamide containing protocol. Expression of c-myc, Ha-ras, and p53 genes was investigated 1/2, 1, 3, 6, 12, 24 hours, 2 6 30 days, 6, and 12 months after treatment with a single dose of ABVD protocol. RNA was isolated from the thymus, spleen, liver, bone marrow, kidneys, and hybridzed with chemiluminescently labelled probes of Ha-ras, c-myc, and p53 genes. Significant changes of gene expression was found in the spleen and thymus, even after 30 minutes. The female spleen seemed to be more sensitive than the male one, but no sex difference was observed in the thymus. No significant alteration was detected in the other investigated organs.

Animals↗

PubMedDate not supplied

Early effect of cyclophosphamide on oncogene expression in vivo.

Cyclophosphamide (CP) is a widely used chemotherapeutic drug, with proven carcinogenic effects. Secondary tumours induced by CP are kidney tumours in humans and haemopoietic malignancies in rodents. Previous experiments have shown its effect on H-ras, c-myc and p53 gene expression in long term in vivo experiments. Our model was developed to analyse the events in the first 24 hours after the administration of CP in short term experiments. The expression of Ha -ras, c-myc and p53 was investigated in the target organs during and up to 24 hours after the administration, at 0.25, 0.5, 1, 6, 12 and 24 h. Since the majority of CP-induced tumours are leukemias and lymphomas in the CBA/Ca mouse model, RNA was obtained from the thymus and the spleen. The results show that p53 is strongly expressed in the thymus during the focused period. On the other hand, the samples were subjected to in situ hybridisation and compared with the results of in situ hybridisation of lung and liver samples. Comparing the results of total RNA and in situ hybridisation should prove useful if the total RNA signal is too weak or not detectable at all. The in situ hybridisation picture showed many positive cells without high expression of oncogenes. Further flow-cytometric studies are necessary to provide a full explanation of the mechanism of CP induced changes.

Animals↗

PubMedDate not supplied

In vivo effects of CHOP protocol on onco and suppressor gene expression: follow-up study.

In vivo investigation of onco/suppressor gene effects may provide new findings concerning chemical carcinogenesis. In earlier studies we pointed out the carcinogenic potential of COPP and ABVD chemotherapeutical protocols in "long-term" experiments. In another follow up study we proved the connection between the early gene expression changes and the late consequences of COPP and ABVD treatment during, a one year latency period. CHOP protocol is containing both proved carcinogenic cyclophosphamide and highly mutagenic doxorubicyn. CHOP protocol in "short-term" experiments shows strong effect on Ha-ras oncogene expression.

Animals↗