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ABSTRACT: Balloon angioplasty and stenting of extracranial carotid artery stenosis can be considered for symptomatic patients, if surgery carries an excessive risk or is contraindicated, if the location of the stenosis is inaccessible to surgical procedures, or the neck is scarred or damaged by radiation therapy. The indications of vertebrobasilar stenosis have not become established, but the treatment has been applied in TIA cases of the vertebrobasilar region, when the patient has presented symptoms of disturbances of cerebral circulation and there has been an at least 70 percent stenosis of the dominant vertebral artery.
Duodecim; lääketieteellinen aikakauskirja 01/2010; 126(8):945-55.
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ABSTRACT: To evaluate the value of preoperative embolization of the inferior mesenteric artery (IMA) before endovascular repair of an abdominal aortic aneurysm.
From January 2000 to October 2006, 79 patients (mean age, 72.3 years; 69 men) scheduled for endovascular aneurysm repair (EVAR) were found to have a patent IMA at computed tomography. Coil embolization of the patent IMA was performed in 40 patients at Kuopio University Hospital, and their outcome was compared with that of 39 patients with a patent IMA who underwent EVAR at Oulu University Hospital without preoperative IMA embolization (control group). All patients were treated with a Zenith stent-graft. The mean follow-up time was 3.4 years +/- 1.7 (median, 3.1 years; range, 0-7.6 years).
There were significantly fewer type II endoleaks in the IMA embolization group than in the control group (25% vs 59%, respectively; P = .002). Preoperative IMA embolization did not correlate with aneurysm size change. The overall linearized aneurysm shrinkage rate per year was 1.4 mm per year +/- 3.8 in the IMA embolization group and 1.7 mm per year +/- 2.4 in the control group (P = .72).
Preoperative coil embolization of the IMA reduced the frequency of type II endoleaks after EVAR, but the authors failed to show any influence on late postoperative aneurysm shrinkage.
Journal of vascular and interventional radiology: JVIR 12/2009; 21(2):181-5. · 1.81 Impact Factor
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ABSTRACT: The aim of this study was to retrospectively evaluate three risk scoring methods in predicting outcome after elective endovascular repair of an abdominal aortic aneurysm.
A Zenith stent graft was employed in 205 patients during years 2001-2005.
The 30-day postoperative mortality rate was 2.9%. Receiver operating characteristics (ROC) curve analysis showed that the Glasgow aneurysm score (GAS) (AUC: 0.843, p=0.004) and the Giles' score (AUC 0.815, p=0.009) had a rather large area under the curve in predicting 30-day mortality rate. The modified Leiden score was much less accurate (AUC: 0.594). The best cut-off value for the GAS in predicting 30-day mortality was 90 (0.6% vs. 17.9%, p<0.0001). Patients with a GAS > or = 90 had a 4-year survival rate of 56.8%, whereas it was 78.5% among those with a lower GAS (p = 0.001). The best cut-off value for the Giles' score was 11 (1.3% vs. 8.3%, p<0.0001). Patients with a Giles' score > or = 11 had a 4-year survival rate of 63.9%, whereas it was 79.0% among those with a lower score (p = 0.016).
The GAS and Giles' risk scoring methods are good predictors of poor immediate and late outcome after EVAR.
Scandinavian cardiovascular journal: SCJ 12/2009; 44(2):125-8. · 1.07 Impact Factor
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ABSTRACT: To evaluate the prevalence of anatomical variations in the circle of Willis predisposing to cerebral ischemia during intraoperative closure of a carotid artery.
Anatomy of the cerebral arteries of 92 deceased was assessed by angiography and permanent silicone casts. Cerebral ischemia during closure of a carotid artery with patent contralateral internal carotid artery (ICA) was considered possible in cases of simultaneous nonfunctioning anterior communicating artery (diameter <0.5 mm) and ipsilateral posterior communicating artery (PComA) (diameter <0.5 mm or fetal type posterior cerebral artery). In cases of contralateral ICA occlusion, cerebral ischemia was considered possible if ipsilateral PComA was nonfunctioning.
Cerebral ischemia during closure of the right or left carotid artery with patent contralateral ICA was estimated to be possible in 16 (17.4%) and 13 (14.1%) cases. In cases of occluded contralateral ICA, the corresponding numbers were 55 (59.8%) and 49 (53.3%). A review of magnetic resonance and catheter angiographies also identified other variants of the circle of Willis with increased risk.
Incomplete circle of Willis predisposes approximately one-sixth of individuals to cerebral ischemia during transient closure of carotid artery but the risk is more than threefold in case of contralateral ICA occlusion.
Acta Neurochirurgica 09/2009; 151(9):1099-105. · 1.52 Impact Factor
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ABSTRACT: The purpose of this study was to report our experience in treating type II endoleaks after endovascular aneurysm repair (EVAR) of abdominal aortic aneurysms. Two hundred eighteen patients underwent EVAR with a Zenith stent-graft from January 2000 to December 2005. During a follow-up period of 4.5 + or - 2.3 years, solely type II endoleak was detected in 47 patients (22%), and 14 of them underwent secondary interventions to correct this condition. Ten patients had transarterial embolization, and four patients had translumbar/transabdominal embolization. The embolization materials used were coils, thrombin, gelatin, Onyx (ethylene-vinyl alcohol copolymer), and glue. Disappearance of the endoleak without enlargement of the aneurysm sac after the first secondary intervention was achieved in only five of these patients (5/13). One patient without surveillance imaging was excluded from analyses of clinical success. After additional interventions in four patients and the spontaneous disappearance of type II endoleak in two patients, overall clinical success was achieved in eight patients (8/12). One patient did not have surveillance imaging after the second secondary intervention. Clinical success after the first secondary intervention was achieved in two patients (2/9) in the transarterial embolization group and three patients (3/4) in the translumbar embolization group. The results of secondary interventions for type II endoleak are unsatisfactory. Although the small number of patients included in this study prevents reliable comparisons between groups, the results seem to favor direct translumbar embolization in comparison to transarterial embolization.
CardioVascular and Interventional Radiology 09/2009; 33(2):278-84. · 2.09 Impact Factor
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ABSTRACT: To assess the midterm results of endovascular repair of abdominal aneurysm (AAA) with a Zenith stent-graft.
Between January 2001 and December 2005, a Zenith stent-graft was employed for endovascular repair of an infrarenal AAA in 206 patients. The mean patient age (+/-standard deviation) was 73.2 years +/- 7.3. Bifurcated grafts were used in 196 patients (96.1%), aortouni-iliac grafts were used in seven patients (3.4%), and a tubular graft was used in one patient (0.5%). The mean follow-up period was 2.4 years +/- 1.7.
The 30-day mortality rate was 2.9%. The overall survival rates at 1-, 3-, and 5-year follow-up were 93.3%, 78.7%, and 64.5%, respectively. None of the patients died of AAA rupture. The primary and assisted technical success rates 1 week after endovascular aneurysm repair were 82.0% and 90.3%. The primary clinical success rates at the 1-, 3-, and 5-year follow-up were 90.6%, 85.6%, and 83.5%. Twenty-seven patients (13.1%) underwent a secondary intervention during the study period.
An 83% rate of freedom from repeat vascular intervention over a period of 5 years as well as an absence of structural failures or aneurysm ruptures demonstrates that a Zenith stent-graft is associated with good midterm results.
Journal of vascular and interventional radiology: JVIR 03/2009; 20(4):448-54. · 1.81 Impact Factor
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ABSTRACT: According to nationally consistent guidelines for nonurgent care, the aim is to make decisions of treatment and prioritizing on systematically clear grounds both within the public and the private sector. In vascular surgery, vertical prioritizing has been carried out and attempts have been made to extensively assess the effectiveness of therapy. We aim to provide a review of the current state of vascular surgery and the resulting health benefit by using the available rough effectiveness indicators, as a register for national quality assurance is lacking.
Duodecim; lääketieteellinen aikakauskirja 02/2009; 125(4):448-55.
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Anna Ketola,
Ari Hinkkanen,
Felicitas Yongabi,
Petra Furu,
Ann-Marie Määttä,
Timo Liimatainen,
Risto Pirinen,
Marko Björn,
Tanja Hakkarainen, Kimmo Mäkinen,
Jarmo Wahlfors,
Riikka Pellinen
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ABSTRACT: Oncolytic viruses are a promising tool for treatment of cancer. We studied an oncolytic Semliki Forest virus (SFV) vector, VA7, carrying the enhanced green fluorescent protein gene (EGFP), as a novel virotherapy candidate against unresectable osteosarcoma. The efficiency and characteristics of the VA7-EGFP treatment were compared with a widely studied oncolytic adenovirus, Ad5Delta24, both in vitro and in vivo. VA7-EGFP resulted in more rapid oncolysis and was more efficient at low multiplicities of infection (MOI) when compared with Ad5Delta24 in vitro. Yet, in MG-63 cells, a subpopulation resistant to the VA7-EGFP vector emerged. In subcutaneous human osteosarcoma xenografts in nude mice treatment with either vector reduced tumor size, whereas tumors in control mice expanded quickly. The VA7-EGFP-treated tumors were either completely abolished or regressed to pinpoint size. The efficacy of VA7-EGFP vector was studied also in an orthotopic osteosarcoma nude mouse model characterized by highly aggressive tumor growth. Treatment with oncolytic SFV extended survival of the animals significantly (P < 0.01), yet none of the animals were finally cured. Sera from SFV-treated mice contained neutralizing antibodies, and as nude mice are not able to establish IgG response, the result points out the role of IgM class antibodies in clearance of virus from peripheral tumors. Furthermore, biodistribution analysis at the survival end point verified the presence of virus in some of the brain samples, which is in line with previous studies demonstrating that IgG is required for clearance of SFV from central nervous system.
Cancer Research 11/2008; 68(20):8342-50. · 7.86 Impact Factor
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Ann-Marie Määttä, Kimmo Mäkinen,
Anna Ketola,
Timo Liimatainen,
Felicitas Newu Yongabi,
Markus Vähä-Koskela,
Risto Pirinen,
Outi Rautsi,
Riikka Pellinen,
Ari Hinkkanen,
Jarmo Wahlfors
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ABSTRACT: We evaluated the therapeutic potential of the replication competent vector VA7-EGFP, which is based on the avirulent Semliki Forest virus (SFV) strain A7 (74) carrying the EGFP marker gene in an orthotopic lung cancer tumor model in nude mice. We have previously shown that this oncolytic vector destroys tumor cells efficiently in vitro and in vivo (in subcutaneous tumor model). Tumor growth in animals with orthotopically implanted adenocarcinoma cells (A549) were monitored during the study with small animal CT. We show that locally administered virotherapy with VA7-EGFP increased survival rate in experimental lung cancer significantly (p < 0.001) comparable to results obtained with the second generation conditionally replicating adenoviral vector Ad5-Delta24TK-GFP, used for comparison. The limited efficacy in systemically administered oncolytic viruses is the essential problem in oncolytic virotherapy and also in this study we were not able to elicit significant response with systemic administration route. Despite the fact that tumor microenvironment in orthotopic lung cancer is more optimal, viruses failed to home to the tumors and were unable to initiate efficient intratumoral replication. Clearly, the efficacy of virotherapy is influenced by many factors such as the route of virus administration, immunological and physiological barriers and cancer cell-specific features (IFN-responsiveness).
International Journal of Cancer 10/2008; 123(7):1704-11. · 5.44 Impact Factor
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ABSTRACT: Symptomatic abdominal aortic aneurysms (AAA) account for up to 20% of patients with unruptured AAA undergoing open repair. This condition is associated with an average postoperative mortality rate after open repair of about 16%. The aim of this study was to evaluate the outcome of a consecutive series of patients who underwent endovascular repair for symptomatic, unruptured AAA.
From January 2000 to October 2006, 14 patients underwent endovascular repair of intact AAA within 15 days since admission for AAA-related symptoms. In these patients, a Zenith stent-graft (Cook Incorporated, Bloomington, IN, USA) was deployed at the Oulu University Hospital, Kuopio University Hospital and Helsinki University Hospital, Finland.
Stent-grafting was not successful in one patient because of access failure. The procedure was immediately converted to open repair and an aortobifemoral bypass with a Dacron prosthesis was performed. In the remaining 13 patients, bifurcated Zenith stent-grafts were deployed. After the procedure, type II endoleak was observed in three patients. The mean follow-up time was 1.9+/-1.4 years. The 2-year survival rate was 69%. The survival freedom from secondary procedure was 71% as one patient underwent stent-grafting for a distal type I endoleak 5 months after the procedure. Another patient underwent femoro-femoral cross-over bypass surgery because of right limb graft thrombosis which occurred 9 months after the procedure.
These preliminary results suggest that endovascular repair of symptomatic, unruptured AAA is feasible and can be associated with a favourable outcome despite a very high operative risk.
Scandinavian Cardiovascular Journal 07/2008; 42(3):178-81. · 0.93 Impact Factor
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ABSTRACT: To evaluate the utility of endovascular salvage of nonmaturing autogenous hemodialysis fistulas in a prospective trial of consecutive patients compared with a historical group of patients who underwent treatment of failing mature autogenous fistulas.
During a 12-year period, angiography revealed anatomic lesions in 75 fistulas with maturing problems (72 radiocephalic and three brachiocephalic). Endovascular therapy through antegrade arterial access was attempted in 72 fistulas. A series of 45 consecutive patients who underwent endovascular salvage of failing mature fistulas was used as a control group.
A technical success rate of 88% (66 of 75) and a clinical success rate of 87% (65 of 75) were achieved for the nonmaturing fistulas. Including the secondary interventions, the rate of complications was 6.1% (eight of 131). By Kaplan-Meier analysis, the primary clinical patency rates were 43% +/- 6% (+/-SEM), 36% +/- 6%, and 23% +/- 6%, and the secondary patency rates were 76% +/- 5%, 68% +/- 6%, and 57% +/- 8% at 6, 12, and 36 months, respectively. A small inflow artery (<3 mm in diameter) predicted a poorer primary patency rate (28% +/- 10% vs 48% +/- 9% at 1 year; P = .01). The secondary patency rate of nonmaturing fistulas at 3 years was worse than that of mature fistulas, at 57% +/- 8% versus 79% +/- 8% (P = .02).
A functional fistula was achieved in 87% of nonmaturing fistulas. Although the functional time gained in these fistulas is shorter than that gained in failing mature fistulas, more than half of nonmaturing fistulas are functional after 3 years.
Journal of Vascular and Interventional Radiology 06/2008; 19(6):870-6. · 2.08 Impact Factor
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Ann-Marie Määttä,
Timo Liimatainen,
Tiina Wahlfors,
Thomas Wirth,
Markus Vähä-Koskela,
Linda Jansson,
Piia Valonen,
Katja Häkkinen,
Outi Rautsi,
Riikka Pellinen, Kimmo Mäkinen,
Juhana Hakumäki,
Ari Hinkkanen,
Jarmo Wahlfors
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ABSTRACT: Semliki Forest virus (SFV) is one of the latest candidates for a virotherapeutic agent against cancer, and recent studies have demonstrated its efficacy in tumor models. In the present study, we examined the antitumor efficacy of an avirulent SFV strain A7(74) and its derivative, a replication-competent SFV vector VA7-EGFP, in a partially immunodeficient mouse tumor model (subcutaneous A549 human lung adenocarcinoma in NMRI nu/nu mouse) and in an immunocompetent rat tumor model (intracranial BT4C glioma in BDIX rat). When subcutaneous mouse tumors were injected 3 times with VA7-EGFP, intratumorally treated animals showed almost complete inhibition of tumor growth, while systemically treated mice displayed only delayed tumor growth (intravenous injection) or no response at all (intraperitoneal injection). This was at least partially due to a strong type I interferon (IFN) response in the tumors. The animals did not display any signs of abnormal behavior or encephalitis, even though SFV-positive foci were detected in the brain after the initial blood viremia. Intracranial rat tumors were injected directly with SFV A7(74) virus and monitored with magnetic resonance imaging. Tumor growth was significantly reduced (p < 0.05) with one virus injection, but the tumor size continued to increase after a lag period and none of the treated animals survived. Three virus injections or T-cell suppression with dexamethasone did not significantly improve treatment efficacy. It appeared that the local virotherapy induced extensive production of neutralizing anti-SFV antibodies that most likely contributed to the insufficient treatment efficacy. In conclusion, we show here that SFV A7(74) is a potential oncolytic agent for cancer virotherapy, but major immunological hurdles may need to be overcome before the virus can be clinically tested.
International Journal of Cancer 09/2007; 121(4):863-70. · 5.44 Impact Factor
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Duodecim; lääketieteellinen aikakauskirja 02/2007; 123(1):47-52.
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ABSTRACT: The efficacy of the most commonly used form of suicide gene therapy, the HSV-TK/GCV method, utilizing herpes simplex virus thymidine kinase (HSV-TK) and antiviral drug ganciclovir (GCV) has been demonstrated in clinical trials. However, safer delivery of the therapeutic gene and more controlled regulation of the transgene expression, the essential prerequisites for successful therapeutic use, are still needed. We describe improved suicide gene therapy against cancer through transcripitional targeting by a strong and selective tumor-specific human hexokinase II promoter (hHKII). We examined the targeting properties of the human hHKII promoter in different human non-small cell lung cancer (NSCLC) and other human cancer cell lines using self-inactivating, VSV-G pseudotyped lentiviral vector. To confirm accurate transcriptional targeting of the hHKII promoter, the lack of transgene expression was verified in human primary bronchial epithelial and bronchial fibroblast cells. Furthermore, tissue-specific expression of the promoter was confirmed using transgenic mouse lines carrying the hHKII promoter driven luciferase reporter gene. We also tested the efficacy of the HSV-TK/GCV suicide gene therapy with the hHKII targeted lentiviral vector to NSCLC cells. Our results show that the hHKII promoter is strongly expressed in cancer cells. The targeted vector with the shortest hHKII promoter fragment (352 bp) appeared to have the best targeting properties because it efficiently governed the expression of the therapeutic gene in cancer cell lines, especially in certain non-small cell lung cancer cell lines, the transgene expression in human primary cells was virtually undetectable, and expression of the proximal hHKII promoter in transgenic mice was very low in most tissues. Also, the anti-cancer efficacy of HSV-TK/GCV therapy with the hHKII-targeted vector was comparable to that obtained with the control vector that utilized a commonly used constitutive promoter from the human elongation factor 1 alpha (hEF1alpha) gene. In conclusion, the transcriptionally targeted lentivirus vector with hHKII promoter can successfully direct HSV-TK/GCV suicide gene therapy to non-small cell lung cancer and other tumor cell types. These results warrant further studies with orthotopic animal tumor models and primary human cancer material.
International Journal of Molecular Medicine 12/2006; 18(5):901-8. · 1.98 Impact Factor
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ABSTRACT: Despite of more than 500 gene therapy trials worldwide very little systematic safety information is available from gene therapy. Safety information was collected from 146 consecutive patients who participated in three randomized, controlled phase II gene therapy trials in cardiovascular diseases and malignant glioma using adenoviruses, plasmid/liposomes and retrovirus packaging cells. Total follow-up time of the patients was 78794 days which equals 1.5 years per patient. The main outcome measures were serious adverse events, other adverse events and changes in general laboratory parameters. Except fever and increases in CRP values plasmid/liposomes were safe and well tolerated. The incidence of serious adverse events in adenovirus-treated patients was 0.9 and 4.0/10000 patient days in cardiovascular and malignant glioma trials as compared to 0.5 and 2.1 in randomized control patients, respectively. Transient fever, leukopenia and increases in CRP and liver enzymes were detected in virus-treated patients. No deaths from side effects or no new cancers were associated with gene therapy. It is concluded that gene therapy, like any other therapy, is associated with side effects which depend on the administered vector, dose, and route of delivery and properties of the transgene. However, given the limitations of this study and length of the follow-up, the safety profile of gene therapy seems to be acceptable for the treatment of severe human diseases.
Current Drug Safety 09/2006; 1(3):253-7.
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ABSTRACT: Lung cancer is a group of diseases that are difficult to cure and new treatment modalities, like gene therapy are actively tested to find alternatives for currently used strategies. Herpes simplex virus thymidine kinase/ganciclovir (HSV-TK/GCV) method is one of the most frequently utilized forms of gene therapy and it has been tested on lung cancer, but no systematic study with comparison of different lung cancer types has been published. In this study, we examined in vitro and in vivo how good targets non-small cell lung cancer (NSCLC) cell lines representing adenocarcinoma, squamous cell lung cancer and large cell lung cancer are for adenovirus-mediated HSV-TK/GCV gene therapy. By using an adenovirus vector carrying a fusion gene of HSV-TK and green fluorescent protein (GFP), we found that: a) adenoviruses were efficient gene transfer vehicles for all types of NSCLCs; b) all adenocarcinoma and large cell lung cancer cells were good targets for HSV-TK/GCV therapy, whereas one of the squamous cell carcinoma cell lines was not responsive to the treatment; c) bystander effect played a major role in the success of this gene therapy form; d) subcutaneous tumors representing all three NSCLC types were efficiently treated with adenovirus-mediated HSV-TK/GCV gene therapy. In summary, this form of gene therapy appeared to be efficient treatment for human NSCLC and these results warrant further studies with primary lung cancer cells and orthotopic lung tumor models.
International Journal of Oncology 05/2004; 24(4):943-9. · 2.40 Impact Factor
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Duodecim; lääketieteellinen aikakauskirja 02/2004; 120(12):1490-3.
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ABSTRACT: Vascular endothelial growth factor (VEGF) gene therapy may be useful for the treatment of lower-limb ischemia. The objectives of this study were to evaluate safety and angiographic and hemodynamic responses of local catheter-mediated VEGF gene therapy in ischemic lower-limb arteries after percutaneous transluminal angioplasty (PTA). For this study, we recruited patients with chronic lower-limb ischemia and atherosclerotic infrainguinal occlusion or stenosis suitable for PTA. In the study, 18 patients received 2x10(10) plaque-forming units (pfu) VEGF-adenovirus (VEGF-Ad), 17 patients received VEGF-plasmid/liposome (VEGF-P/L; 2000 microg of VEGF plasmid, 2000 microl of DOTMA:DOPE), and 19 control patients received Ringer's lactate at the angioplasty site. Digital subtraction angiography (DSA) was used to evaluate vascularity before, immediately after, and 3 months after the PTA. Clinical follow-up data, basic laboratory tests, and ankle-brachial index (ABI) were evaluated. Primary endpoint was DSA analysis of vascularity, and secondary endpoints were restenosis rate, Rutherford class, and ABI after 3 months follow-up. No major gene transfer-related side effects or differences in laboratory tests were detected between the study groups. However, anti-adenovirus antibodies increased in 61% of the patients treated with VEGF-Ad. For the primary endpoint, follow-up DSA revealed increased vascularity in the VEGF-treated groups distally to the gene transfer site (VEGF-Ad P=0.03, VEGFP/L P=0.02) and in the VEGF-Ad group in the region of the clinically most severe ischemia (P=0.01). As for the secondary endpoints, mean Rutherford class and ABI showed statistically significant improvements in the VEGF-Ad and VEGF-P/L groups, but similar improvements were also seen in the control patients. We conclude that catheter-mediated VEGF gene therapy is safe and well tolerated. Angiography demonstrated that VEGF gene transfer increased vascularity after PTA in both VEGF-Ad- and VEGF-P/L-treated groups.
Molecular Therapy 08/2002; 6(1):127-33. · 6.87 Impact Factor
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ABSTRACT: Arterial smooth muscle cell (SMC) migration and proliferation are central features in atherogenesis. Altered gene expression and cell proliferation in atherosclerotic lesions have some similar characteristics with certain solid tumors and thus might have similar mechanisms that lead to SMC proliferation. Among cancer cells common features are genome-wide hypomethylation which correlates with transformation and tumor progression, and coincident overexpression of methyltransferase (MTase). The purpose of the present study was to analyze whether alterations in DNA methylation and MTase expression are present in atherosclerotic lesions. A significant reduction in genomic 5-methylcytosine content was detected in advanced human atherosclerotic lesions and in lesions of ApoE knock-out mice. SMC were shown to develop hypomethylation in vitro during transformation from a contractile to synthetic phenotype. Balloon denudation of New Zealand White rabbit aorta caused proliferation of intimal SMC with concomitant genomic hypomethylation in the thickened intima. By using in situ hybridization the overall transcriptional activity was found to be increased in clusters of lesion SMC. Marked heterogeneity was seen in MTase mRNA expression in various types of atherosclerotic lesions among intimal and medial SMC. These findings show that (1) genomic hypomethylation occurs during atherogenesis in human, mouse and rabbit lesions and that it correlates with increased transcriptional activity; (2) MTase is expressed in atherosclerotic lesions; and (3) hypomethylation is present in advanced lesions at the same level as in malignant tumors and may affect cellular proliferation and gene expression in atherosclerotic lesions.
Vascular Medicine 03/2002; 7(1):5-11. · 1.46 Impact Factor
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ABSTRACT: Previous studies have shown that, cultured rat pancreatic carcinoma cells, derived from azaserine-induced acinar tumours, yield tumours with a ductal phenotype.
In order to find out the molecular characteristics of this tumour model, tumour suppressor protein (p53), apoptosis inhibiting protein (Bcl-2) and proliferating cell nuclear antigen (PCNA) expressions were analysed in rat pancreatic and subcutaneous tumours, as well as in normal rat pancreas.
Immunoreactivity for p53 protein was found in 86% of intrapancreatic tumours and in 100% of subcutaneous tumours. The average fraction of positive carcinoma cells was over 50%. Normal rat pancreas showed only slight positive or negative staining for p53. Bcl-2 did not show positive immunoreactivity in rat tumour samples. For PCNA all tumour samples showed positive staining. Also normal pancreas of 6-week-old animals were clearly positive, whereas the samples of the older animals were only slightly positive.
Possible mutations in the p53 tumour suppressor gene and a strong expression of PCNA were shown in carcinoma cell line-induced rat pancreatic tumours. These features of the rat pancreatic tumour model resemble human pancreatic carcinoma and may favour the use of this model in pancreatic cancer studies.
Anticancer research 27(1A):23-6. · 1.73 Impact Factor
