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M Johansson

Publications and source records attributed to M Johansson.

At least 19 recordsLinked to original sources
PubMed2006

Enhanced toxicity of purine nucleoside analogs in cells expressing Drosophila melanogaster nucleoside kinase mutants.

The multisubstrate deoxyribonucleoside kinase of Drosophila melanogaster (Dm-dNK) is investigated for possible use as a suicide gene in combined gene/chemotherapy of cancer. The enzyme has broader substrate specificity and higher catalytic rate compared to herpes simplex type 1 thymidine kinase and other known dNKs. Although the enzyme has broad substrate specificity, it has a preference for pyrimidine nucleosides and nucleoside analogs. We have evaluated the substrate specificity and kinetic properties of Dm-dNK proteins containing M88R, V84A+M88R or V84A+M88R+A110D mutations in the amino-acid sequence. These engineered enzymes showed a relative increase in phosphorylation of purine nucleoside analogs such as ganciclovir, 9-beta-D-arabinofuranosylguanine and 2',2'-difluorodeoxyguanosine compared to the wild-type enzyme. The mutant enzymes were expressed in an osteosarcoma thymidine kinase-deficient cell line and the sensitivity of the cell line to nucleoside analogs was determined. The cells expressing the M88R mutant enzyme showed the highest increased sensitivity to purine nucleoside analogs with 8- to 80-fold decreased inhibition constant IC(50) compared to untransduced control cells or cells expressing the wild-type nucleoside kinase. In summary, our data show that enzyme engineering can be used to shift the substrate specificity of the Dm-dNK to selectively increase the sensitivity of cells expressing the enzyme to purine nucleoside analogs.

Amino Acid Sequence↗
PubMed2006

Protein expression in experimental malignant glioma varies over time and is altered by radiotherapy treatment.

Radiotherapy is one of the mainstays of glioblastoma (GBM) treatment. This study aims to investigate and characterise differences in protein expression patterns in brain tumour tissue following radiotherapy, in order to gain a more detailed understanding of the biological effects. Rat BT4C glioma cells were implanted into the brain of two groups of 12 BDIX-rats. One group received radiotherapy (12 Gy single fraction). Protein expression in normal and tumour brain tissue, collected at four different time points after irradiation, were analysed using surface enhanced laser desorption/ionisation - time of flight - mass spectrometry (SELDI-TOF-MS). Mass spectrometric data were analysed by principal component analysis (PCA) and partial least squares (PLS). Using these multivariate projection methods we detected differences between tumours and normal tissue, radiation treatment-induced changes and temporal effects. 77 peaks whose intensity significantly changed after radiotherapy were discovered. The prompt changes in the protein expression following irradiation might help elucidate biological events induced by radiation. The combination of SELDI-TOF-MS with PCA and PLS seems to be well suited for studying these changes. In a further perspective these findings may prove to be useful in the development of new GBM treatment approaches.

Animals↗
PubMed2006

Population analysis of the pharmacokinetics and the haematological toxicity of the fluorouracil-epirubicin-cyclophosphamide regimen in breast cancer patients.

PURPOSE: The aims of the study were (a) to characterise the pharmacokinetics (PK), including inter-individual variability (IIV) and inter-occasion variability (IOV) as well as covariate relationships and (b) to characterise the relationship between the PK and the haematological toxicity of the component drugs of the fluorouracil (5-FU)-epirubicin (EPI)-cyclophosphamide (CP) regimen in breast cancer patients. PATIENTS AND METHODS: Data from 140 breast cancer patients, either within one of different studies or in routine clinical management, were included in the analyses. The patients were all treated with the fluorouracil-epirubicin-cyclophosphamide (FEC) regimen every third week for 3-12 courses, either in standard doses, i.e. 600/60/600 mg/m(2) of 5-FU, EPI and CP, respectively, or according to a dose escalation/reduction protocol (tailored dosing). PK data were available from 84 of the patients, whereas time-courses of haematological toxicity were available from 87 patients. The data analysis was carried out using mixed effects models within the NONMEM program. RESULTS: The PK of 5-FU, EPI and 4-hydroxy-cyclophosphamide (4-OHCP), the active metabolite of CP, were described with a one-compartment model with saturable elimination, a three-compartment linear model and a two-compartment linear model, respectively. No clinical significant correlation was found between PK across drugs. The unexplained variability in clearance was found to be less within patients, between courses (inter-occasion variability, IOV) than between patients (inter-individual variability, IIV) for EPI and 5-FU. For 4-OHCP, however, the IIV diminished by approximately 45% when significant covariates were included and the final population model predicts an IIV that is equal to IOV. Significant covariates for elimination capacity parameters were serum albumin (5-FU, EPI and 4-OHCP), creatinine clearance (5-FU), bilirubin (EPI) and body surface area (BSA) (4-OHCP). Elimination capacity of 5-FU and EPI was not related to BSA and for none of the studied drugs did body weight explain the PK variability. The time-course of haematological toxicity after treatment was well described by a semi-physiological model that assumes additive haematological toxicity between CP and EPI with negligible contribution from 5-FU. The influence of G-CSF could be incorporated into the model in a mechanistic manner as shortening the maturation time to 43% of the normal duration and increasing the mitotic activity to 269% of normal activity. CONCLUSIONS: The models presented describe the dose-concentration-toxicity relationships for the FEC therapy and may provide a basis for implementation and comparison of different individualisation strategies based on covariates, therapeutic drug monitoring and/or pharmacodynamic (PD) feedback. The PD model extends on previous semi-mechanistic models in that it also takes G-CSF administration into account.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

Randomized clinical trial of day-care versus overnight-stay laparoscopic cholecystectomy.

BACKGROUND: Laparoscopic cholecystectomy has been performed as a day-care procedure for many years. Few studies have been conducted with primary focus on patient acceptance and preferences in terms of quality of life for this practice compared with overnight stay. METHODS: Data from 100 patients with symptomatic gallstones randomized to laparoscopic cholecystectomy performed either as a day-care procedure or with overnight stay were analysed. Complications, admissions and readmissions, quality of life and health economic aspects were assessed. Two instruments were used to assess quality of life, the Hospital Anxiety and Depression Scale (HADS) and the Psychological General Well-Being Index (PGWB). RESULTS: Forty-eight (92 per cent) of 52 patients in day-care group were discharged 4-8 h after the operation. Forty-two (88 per cent) of 48 in the overnight group went home on the first day after surgery. The overall conversion rate was 2 per cent. Two patients had complications after surgery, both in the day-care group. No patient in either group was readmitted. There was no significant difference in total quality of life score between the two groups. The mean direct medical cost per patient in the day-care group (3085 Euros) was lower than that in the overnight group (3394 Euros). CONCLUSION: Laparoscopic cholecystectomy can be performed as a day-case procedure with a low rate of complications and admissions/readmissions. Patient acceptance in terms of quality of life variables is similar to that for cholecystectomy with an overnight stay. The day-care strategy is associated with a reduction in cost.

Adolescent↗
PubMed2006

The OSBP-related proteins (ORPs): global sterol sensors for co-ordination of cellular lipid metabolism, membrane trafficking and signalling processes?

Protein families related to OSBP (oxysterol-binding protein) are present in eukaryotes from yeast to human. The functions of the ORPs (OSBP-related proteins) have remained largely enigmatic. Even though they have been implicated in the function of ERJs (endoplasmic reticulum junctions), it is evident that any single model for their mechanism of action is insufficient. The existing evidence points in many different directions, such as integration of sterol and sphingomyelin metabolism, regulation of neutral lipid metabolism, control of signalling cascades, regulation of secretory vesicle generation, and function in the microtubule-based motility of endo/lysosomes. Some of these functions could involve ERJ and non-vesicular transport of lipids, but this is unlikely to be the unifying feature. We believe, rather, that the common denominator for ORP function is acting as sterol sensors that relay information to a spectrum of cellular processes.

Animals↗
PubMed2006

Substrate specificity of three viral thymidine kinases (TK): vaccinia virus TK, feline herpesvirus TK, and canine herpesvirus TK.

In search of novel suicide gene candidates we have cloned and characterized thymidine kinases from three viruses; vaccinia virus TK (VVTK), feline herpesvirus TK (FHV-TK), and canine herpesvirus TK (CHV-TK). Our studies showed that VVTK primarily is a thymidine kinase, with a substrate specificity mainly restricted to dThd and only minor affinity for dCyd. VVTK also is related closely to mammalian thymidine kinase 1 (TK1), with 66% identity and 75% general homology. Although CHV-TK and FHV-TK are sequence related to herpes simplex virus types 1 thymidine kinase (HSV1-TK), with 31% and 35% identity and a general similarity of 54%, the substrate specificity of these enzymes was restricted to dThd and thymidine analogs.

Escherichia coli↗
PubMed2006

Lymphatic vessels in pancreatic islets implanted under the renal capsule of rats.

Transplantation of pancreatic islets necessitates an engraftment process, including revascularization of the graft. Studies of graft vasculature have demonstrated that islets become revascularized during the first post-transplant week through an angiogenic process. If this also involves lymphatic vessels is unknown. The aim of the present study was to functionally evaluate if lymphatic vessels, which are absent in endogenous islets, form after islet transplantation. To achieve this, inbred Wistar-Furth rats were transplanted with 250 syngeneic islets under the renal capsule. Intra-vital microscopy of the graft in combination with interstitial injection of Evans Blue was performed 1 week, 1 month or 9-12 months later. In all animals studied, there was drainage through intra-graft lymphatic capillaries emptying into larger lymphatic vessels associated with the renal capsule. The number was slightly lower 1 week post-transplantation. Most of the lymphatic capillaries were present in the graft stroma, rather than interspersed among the endocrine cells. In some animals, we were able to demonstrate dye in regional lymph nodes. We conclude that unlike endogenous islets, islet grafts develop a lymphatic drainage. Its functional importance and characteristics remain to be established. However, it can be speculated that immune reactions may be facilitated by the presence of lymphatic vessels.

Animals↗
PubMed2005

Laparoscopy for abdominal emergencies: evidence-based guidelines of the European Association for Endoscopic Surgery.

BACKGROUND: Emergency laparoscopic exploration can be used to identify the causative pathology of acute abdominal pain. Laparoscopic surgery also allows treatment of many intraabdominal disorders. This report was prepared to describe the effectiveness of laparoscopic surgery compared to laparotomy or nonoperative treatment. METHODS: A panel of European experts in abdominal and gynecological surgery was assembled and participated in a consensus conference using Delphi methods. The aim was to develop evidence-based recommendations for the most common diseases that may cause acute abdominal pain. RECOMMENDATIONS: Laparoscopic surgery was found to be clearly superior for patients with a presumable diagnosis of perforated peptic ulcer, acute cholecystitis, appendicitis, or pelvic inflammatory disease. In the emergency setting, laparoscopy is of unclear or limited value if adhesive bowel obstruction, acute diverticulitis, nonbiliary pancreatitis, hernia incarceration, or mesenteric ischemia are suspected. In stable patients with acute abdominal pain, noninvasive diagnostics should be fully exhausted before considering explorative surgery. However, diagnostic laparoscopy may be useful if no diagnosis can be found by conventional diagnostics. More clinical data are needed on the use of laparoscopy after blunt or penetrating trauma of the abdomen. CONCLUSIONS: Due to diagnostic and therapeutic advantages, laparoscopic surgery is useful for the majority of conditions underlying acute abdominal pain, but noninvasive diagnostic aids should be exhausted first. Depending on symptom severity, laparoscopy should be advocated if routine diagnostic procedures have failed to yield results.

Abdomen↗
PubMed2005

Determination of fentanyl in human plasma and fentanyl and norfentanyl in human urine using LC-MS/MS.

Fentanyl, a potent analgesic drug, has traditionally been used intravenously in surgical or diagnostic operations. Formulations with fentanyl in oral transmucosal delivery system and in transdermal depot-patch have also been developed against breakthrough pain in cancer patients. In this report, LC-MS/MS methods to determine fentanyl in human plasma as well as fentanyl and its main metabolite, norfentanyl, in human urine are presented together with validation data. The validation ranges were 0.020-10.0 and 0.100-50.0 ng/ml for fentanyl in plasma and urine, respectively, and 0.102-153 ng/ml for norfentanyl in urine. Liquid-liquid extraction of the compounds fentanyl, norfentanyl and the deuterated internal standards, fentanyl-d5 and norfentanyl-d5 from the matrixes was applied and separation was performed on a reversed phase YMC Pro C18-column followed by MS/MS detection with electrospray in positive mode. The inter-assay precision (CV%) was better than 4.8% for fentanyl in plasma and 6.2% and 4.7% for fentanyl and norfentanyl, respectively, in urine. The ruggedness of the methods, selectivity, recovery, effect of dilution and long-term stability of the analytes in plasma and urine were investigated. Effect of haemolysis and stability of fentanyl in blood samples were also studied. The methods have been applied for the determination of fentanyl in plasma samples and fentanyl/norfentanyl in urine samples taken for pharmacokinetic evaluation after a single intra-venous (i.v.) dose of 75 microg fentanyl.

Chromatography, Liquid↗
PubMed2005

Oestrogen receptor {alpha} gene polymorphisms in systemic lupus erythematosus.

OBJECTIVE: To analyse associations of two oestrogen receptor alpha (ORalpha) gene polymorphisms in 260 patients with SLE from northern Sweden. The two polymorphisms, PvuII T/C and the XbaI A/G, are located in the first intron of the ORalpha gene. METHODS: All patients fulfilling at least four of the ACR criteria for SLE were consecutively recruited during one year. The SLEDAI score and SLICC damage index were recorded. 670 individuals from the same geographical area served as controls. DNA from the patients and controls was extracted and genotyped using the 5' nuclease assay with an ABI PRISM 7900HT instrument. The genotype/phenotype relationships were calculated using SPSS. RESULTS: The unusual PvuII C allele was associated with malar rash and the unusual XbaI G allele with photosensitivity (p = 0.001, OR = 2.53, 95% CI = 1.43 to 4.47 and p = 0.007, OR = 2.12, 95% CI = 1.22 to 3.66, respectively). The common XbaI AA genotype was associated with serositis (p = 0.013, OR = 1.92, 95% CI = 1.15 to 3.22). Based on the SLICC damage index associations of the common TT genotype and AA genotype with cognitive impairment were identified (p = 0.018, OR = 2.47, 95% CI = 1.17 to 5.25 and p = 0.018, OR = 2.75, 95% CI = 1.19 to 6.38 respectively). There was also an association of the XbaI AA genotype with the angina/coronary artery bypass variable (p = 0.042, OR = 2.58, 95% CI = 1.03 to 6.43). Of the variables describing disease severity and duration it was found that carriers of the unusual PvuII C allele showed a later onset of SLE (p = 0.02) and carriers of the unusual XbaI G allele a lower SLICC damage index. CONCLUSIONS: The unusual PvuII C and XbaI G alleles were associated with a milder form of SLE characterised by skin manifestations, later onset, and less organ damage.

Adult↗
PubMed2005

The establishment of endovascular aneurysm coiling at a neurovascular unit: report of experience during early years.

The treatment of cerebral aneurysms is changing from surgical clipping to endovascular coiling (EVC) in many neurovascular centres. The aim of this study was to evaluate the technical results and clinical outcome at 6 months in a consecutive series of subarachnoid hemorrhage (SAH) patients treated with EVC, in a situation when the EVC had been established very rapidly as the first line of treatment at a neurovascular centre. The patient material comprised 239 SAH patients (155 women and 84 men, mean age 55 years, age range 16-81) allocated to EVC as the first line of treatment in the acute stage (within 3 weeks of rupture) between September 1996 and December 2000. Clinical grade on admission was Hunt & Hess (H&H) I and II in 42%, H&H III in 25% and H&H grade IV and V in 33% of the patients. The aneurysm was located in the anterior circulation in 82% of the cases. EVC was performed on days 0-3 in 77% of the cases. EVC of the target aneurysm was able to be completed in 222 patients (93%). Complete occlusion was achieved in 126 patients (53%). Procedural complications occurred in 39 patients (16%). Favourable clinical outcome was observed in 57%, severe disability in 28% and poor outcome in 14% of the patients. Favourable outcome was achieved in 77% of H&H I and II patients and in 43% of H&H III-V patients. The multivariate logistic regression analysis revealed that younger age, good neurological grade on admission, absence of intracerebral hematoma and intraventricular hematoma respectively, ICA-PcomA aneurysm location, later treatment and absence of complications were significant predictors of favourable outcome. After interventional training and installation of the X-ray system, the introduction and establishment of EVC at a neurovascular unit can be done in a short period of time and with favourable results. Future studies must concentrate on identifying factors of importance for the choice of interventional or surgical therapy. The results of this study indicate that endovascular therapy may be particularly beneficial in poor-grade patients and in patients with aneurysms in the ICA-PcomA territory.

Adolescent↗
PubMed2005

Randomized clinical trial of open versus laparoscopic cholecystectomy in the treatment of acute cholecystitis.

BACKGROUND: The aim of this prospective trial was to determine whether surgical approach (open versus laparoscopic) had an impact on morbidity and postoperative recovery after cholecystectomy for acute cholecystitis. METHODS: Seventy patients who met the criteria for acute cholecystitis were randomized to open or laparoscopic cholecystectomy. The type of operation was unknown to the patient and all hospital staff involved in the postoperative care. RESULTS: The two groups were similar with respect to demographic and clinical characteristics. There were no significant differences in rate of postoperative complications, pain score at discharge and sick leave. In eight patients a laparoscopic procedure was converted to open cholecystectomy. Median operating time was 90 (range 30-155) and 80 (range 50-170) min in the laparoscopic and open groups respectively (P = 0.040). The direct medical costs were equivalent in the two groups. Although median postoperative hospital stay was 2 days in each group, it was significantly shorter in the laparoscopic group (P = 0.011). CONCLUSION: Cholecystectomy for acute cholecystitis can be performed by either laparoscopic or open techniques without any major clinically relevant differences in postoperative outcome. Both techniques offer low morbidity and rapid postoperative recovery.

Adult↗
PubMed2005

The R620W C/T polymorphism of the gene PTPN22 is associated with SLE independently of the association of PDCD1.

The gene PTPN22 is located on chromosome 1p13 and encodes a protein tyrosine phosphatase called the lymphoid-specific phosphatase (Lyp). Lyp is expressed in lymphocytes, where it physically associates through its proline-rich motif (called P1) with the SH3 domain of the protein tyrosine kinase Csk, an important suppressor of the Src family of kinases Lck and Fyn, which mediate TCR signaling. Therefore, it is said that interaction between Lyp and Csk enables these effectors to inhibit T-cell activation synergistically. It was reported that a missense single nucleotide polymorphism , R620W (rs2476601), 1858C->T encodes an amino-acid change in the P1 proline-rich motif of the gene PTPN22 and is associated with SLE in North American white individuals. PTPN22 gene polymorphisms were genotyped in 571 Swedish SLE patients and 1042 healthy controls using TaqMan SNP Genotyping Assay. Differences were observed between cases and control subjects at both the allele (chi(2)=11.2895;P=0.0007,1df) and genotype (chi(2)=10.2243;P=0.0013, 1df) levels. We also found evidence of a genetic association between PTPN22 and renal disorder (chi(2)=9.5660;P=0.0019). We then analyzed if in patients with renal disorder associations with PDCD1 and PTPN22 were independent. Our data suggest that this appears to be the case although we observed some degree of interaction.

Alleles↗
PubMed2005

MRI combined with MR cholangiopancreatography versus helical CT in the evaluation of patients with suspected periampullary tumors: a prospective comparative study.

PURPOSE: To establish the diagnostic accuracy of MRI including MR cholangiopancreatography (MRCP) compared with helical CT in the differentiation of malignant and benign lesions in the periampullary region. MATERIAL AND METHODS: Fifty-one patients (27 M, 24 F, mean age 66 years, range 39-86 years) with obstructive jaundice and sonographic evidence of intra- and extrahepatic bile duct dilatation (n=31) or suspicion of periampullary tumor, based on previously performed ultrasound and/or CT examination (n=20), were studied. MRI with MRCP and helical CT were reviewed blindly under standardized conditions. Lesion status (differentiation of malignant versus benign) was rated on a 5-point diagnostic confidence scale. Reference standards for comparison were findings at surgery or laparoscopy and/ or the clinical outcome. The predictive value of imaging findings was determined with multivariate logistic regression analysis. RESULTS: The areas under the receiver operating characteristic curve were 0.96 for MRI with MRCP and 0.81 for CT (P <0.05). Multivariate analysis of eight imaging variables at MRI indicated that a stricture with malignant characteristics at MRCP was the best predictor of malignancy. CONCLUSION: MRI with MRCP was significantly more accurate than CT in differentiating between malignant and benign lesions in patients with suspected periampullary tumors, mainly due to the information obtained on the MRCP images of the biliary and pancreatic duct anatomy.

Adult↗
PubMed2005

Current asthma and respiratory symptoms among pupils in relation to dietary factors and allergens in the school environment.

UNLABELLED: The aim was to study asthma and allergy in relation to diet and the school environment. Pupils (5-14 years) in eight schools received a questionnaire, 1014 participated (68%). Settled dust was collected on ALK-filters and analyzed for allergens from cat (Fel d 1), dog (Can f 1), horse (Equ cx), house dust mites (Der p 1, Der f 1), and cockroach (Bla g 1) by ELISA. In total, 6.8% reported cat allergy, 4.8% dog allergy, 7.7% doctor's diagnosed asthma and 5.9% current asthma, and 7.8% reported wheeze. Current asthma was less common among those consuming more fresh milk (P < 0.05) and fish (P < 0.01). Poly-unsaturated fatty acids was associated with more wheeze (P < 0.05), olive oil was associated with less doctors' diagnosed asthma (P < 0.05). Totally, 74% of the classrooms had mean CO(2) <1000 ppm. The median concentration per gram dust was 860 ng/g Fel d 1, 750 ng/g Can f 1 and 954 U/g Equ cx. Horse allergen was associated with more wheeze (P < 0.05), daytime breathlessness (P < 0.05), current asthma (P < 0.05) and atopic sensitization (P < 0.05). Dog allergen was associated with wheeze (P < 0.05) and daytime breathlessness (P < 0.05). The associations between allergens and respiratory symptoms were more pronounced among those consuming margarine, not consuming butter, and with a low intake of milk. In conclusion, cat, dog and horse allergens in schools could be a risk factor for asthma and atopic sensitization, and dietary factors may interact with the allergen exposure. PRACTICAL IMPLICATIONS: Previous school studies performed by us in mid-Sweden, showed that most classrooms did not fulfill the ventilation standards. In this study, most of the classrooms fulfilled the ventilation standard, but despite that had widespread allergen contamination. Most previous studies have focused on cat allergen, but our study has shown that also dog and horse allergens can be risk factors for asthma and allergy in schools. As allergens are transported from other environments, mainly the home environment, the main prevention should be to minimize transfer of allergens. This could be achieved by reducing contacts with furry pets and horses, or using different clothes at home and at school (e.g. school uniforms). Increased cleaning in the schools may reduce allergen levels, but the efficiency of this measure must be evaluated in further intervention studies. Finally, our study supports the view that dietary habits among pupils should not be neglected and interaction between dietary factors and indoor allergen exposure needs to be further investigated.

Adolescent↗
PubMed2004

Internal standard in surface-enhanced Raman spectroscopy.

A method is presented for the use of SAM layers as internal standards for calibration in surface-enhanced Raman spectroscopy. Three cyano-containing compounds were attached to gold colloids via a metal-sulfur bond and evaluated for spectral stability and normalization capacity. The results show that the analyte, rhodamine 6G, and the internal standard signal enhancement covaried, and it was possible to quantify the analyte with PLS. The fact that the enhancing substrate was chaotic assemblies with large variation in signal enhancement shows the versatility of this method.

Journal Article↗
PubMed2004

The tyrosine kinase inhibitor ZD6474 inhibits tumour growth in an intracerebral rat glioma model.

Malignant glioma is characterised by extensive neovascularisation, principally influenced by vascular endothelial growth factor (VEGF). ZD6474 is a potent inhibitor of VEGF-R2 tyrosine kinase activity, but with additional inhibitory effects on other growth factors. In this study, we have investigated the effects of ZD6474 with regard to tumour growth, neovascularisation, proliferation and apoptosis in the intracerebral rat glioma model, BT4C. ZD6474 (50 and 100 mg kg(-1)) was given as a daily oral gavage. Animals were killed on day 19 and tumour volume was measured. Sections were stained for factor VIII, Ki-67 and for apoptosis. The ability of ZD6474 to inhibit cell growth directly was examined in vitro, using the glioma cell line BT4C and the transformed rat brain endothelial cell line RBE4. Cell growth was analysed with fluorometric microculture cytotoxicity assay to quantify the cytotoxic effects. ZD6474 significantly decreased tumour volume compared to controls. Microvascular density increased after treatment with ZD6474, and tumour cell proliferation index was reduced. There was also an increase in tumour cell apoptosis. In vitro, the growth of both cell lines was significantly reduced. The results reported justify further experimental investigations concerning the effects of ZD6474 in malignant glioma alone or in combination with other modalities.

Animals↗