Henrik Von Euler - Academia.edu (original) (raw)
Papers by Henrik Von Euler
International journal of oncology, 2009
Thymidine kinase 1 (TK), which is involved in the synthesis of DNA precursors, is only expressed ... more Thymidine kinase 1 (TK), which is involved in the synthesis of DNA precursors, is only expressed in S-G2 cells. Serum TK levels correlate to the proliferative activity of tumor disease. Determinations of TK levels have so far relied on radio enzyme assay (REA) and experimental ELISA methods, which have limited the clinical use of this biomarker, although recent studies in dogs with malignant lymphoma (ML) demonstrate its wide potential. A non-radiometric method based on a competitive immunoassay with specific anti-3'-azido-deoxythymidine monophosphate (AZTMP) antibodies has been further developed into the fully automated Liaison TK assay (DiaSorin). Sera from healthy dogs (n=30), and dogs with leukemia (LEUK) (n=35), ML (n=84), non-hematological tumors (n=50), and inflammatory disease (n=14) were tested using both methods. Lymphoma and LEUK samples were available before and during chemotherapy. The coefficients of variation for the Liaison TK assay in this study were 6.3 and 3.4...
Research in Veterinary Science, 2006
The aim of this study was to evaluate an enzyme-linked immunosorbent assay (ELISA), for determina... more The aim of this study was to evaluate an enzyme-linked immunosorbent assay (ELISA), for determination of serum thymidine kinase 1 (sTK1) activity in dogs with malignant lymphoma (ML) and compare it with a thymidine kinase (TK) radioenzymatic assay (TK-REA). The TK-REA has recently been shown to be useful in determining the clinical stage and prognosis in canine ML. In addition, serum lactate dehydrogenase (LDH) was measured. Forty-five dogs were included in the study. Sixty serum samples from these dogs, stored in a tumour serum sample bank (stored at -20 degrees C), were analysed. Apart from 37 dogs with ML, four normal dogs as well as two dogs with mammary carcinomas, one dog with bladder carcinoma, and one dog with malignant fibrous histiocytoma were included. Staging of ML was based on the modified World Health Organization (WHO) staging system for canine ML. The diagnosis of all tumours was verified by histopathology. The TK activity (units per litre [U/L]) ranged from 1.0 to 607.9 in the TK-REA analysis and from 1.1 to 510 in the TK-ELISA (normal reference value <7U/L). The range for LDH was between 12 and 1194 U/L (normal reference value <228 U/L). There was a significant correlation between the TK-REA and the TK-ELISA. The correlation coefficient (CC) was 0.97 and the standard error of the estimate (SEE) was 3.7 U/L. There was no correlation between LDH and either the TK-REA or the TK-ELISA (CC=0.53 for both assays; SEE=26.7 and 12.7 U/L, respectively). Most of the variation in LDH was still within the normal reference range. The mean LDH in dogs with high-stage (stage IV+V) disease was 201.9 U/L. The corresponding values for the TK-REA and TK-ELISA were 109 and 109.9 U/L, respectively. The significant relation between the TK-REA and the TK-ELISA was confirmed by Bland-Altman analysis. The TK-ELISA assay, because of its relative simplicity, will permit measurement of TK in cases of ML in dogs to become a routine procedure. PMID: 16140350 [PubMed -indexed for MEDLINE] J :595-6. Serum thymidine kinase (sTK) activity was evaluated as a tumor marker for canine malignant lymphoma (ML). The objective was to investigate if sTK, as in humans, could be used as a prognostic marker for survival time in dogs with ML and if sTK could identify early signs of progression of disease in treated dogs. Serum samples from 52 dogs with ML were tested for initial TK activity. Samples from 21 normal dogs and 25 dogs with nonhematologic neoplasms were used for comparison. Forty-four dogs with ML were treated. Serum TK activity was measured in treated dogs before each treatment and every 4 weeks thereafter until relapse. Dogs with ML had 2-180 times higher TK activity (TK 5-900 U/L) than normal dogs (TK <7 U/L) based on the mean + 2 standard deviations. In the group of other neoplasms, only 2 dogs had a moderate increase (6.4 and 7.5 U/L) compared with the controls. Mean sTK activities in the dogs with ML that had gone into complete remission (CR) were not significantly different from activities in healthy controls (P = .68). Mean sTK at least 3 weeks before and at the time of relapse was significantly higher than activity measured at CR (P < .0001). Dogs with ML that initially had sTK >30 U/L had significantly shorter survival times (P < .0001). Furthermore, sTK activity reflected the clinical staging of ML. Measuring sTK can be used as a powerful objective tumor marker for prognosis and for predicting relapse before recurrence of clinically detectable disease in dogs with ML undergoing chemotherapy. PMID: 15515587 [PubMed -indexed for MEDLINE] Abstract:Thymidine kinase 1 (TK), which is involved in the synthesis of DNA precursors, is only expressed in S-G2 cells.
International Journal of Molecular Medicine, 2005
Heterogeneous gene expression in tumours and the degradation of RNA when sampling under non-RNAse... more Heterogeneous gene expression in tumours and the degradation of RNA when sampling under non-RNAse-free conditions may limit the potential benefit of cDNA array studies. This study examines changes in the integrity of RNA by means of RNA gel electrophoresis at various post-operative intervals on canine mammary tumours (n=10) and malignant lymphoma (n=1). The tumours were cut into pieces (3-5 mm diameter, approximately 50 mg) and kept in tubes without RNAse-free buffer at room temperature. No special precautions were taken to avoid the influences of Rnase; rather, normal surgical procedures were used. We found that total RNA of the mammary tumours started to degrade within 30 min of the operation, and the rate of degradation increased up to 4 h, which was the last time point included in this study. RNA in the lymphoma tumours degraded more rapidly, and was completely degraded at 30 min post-operation. The degradation of mRNA in the mammary tumours, as studied by human cDNA arrays, was heterogeneous, i.e. some mRNA degraded completely, some only partially. This indicates that the mRNA degradation rate varied depending on the type of mRNA. However, since we found that gene expression differs depending on the part of the mammary tumour examined, one cannot exclude that the variation in the mRNA degradation rate may simply reflect heterogeneous gene expression within the tumour. We conclude that RNA integrity is unaffected immediately after sampling under non-RNAse-free conditions; however, the tumour sample should be preserved under RNAse-free conditions within 15 min to avoid RNA degradation. This is a much shorter time interval than previously reported in other similar studies; however, these studies generally treated normal tissue, under which 3-5 h non-RNAse-free conditions have been found not to affect RNA quality.
PLoS ONE, 2014
Diabetes mellitus is one of the most common endocrine disorders in dogs and is commonly proposed ... more Diabetes mellitus is one of the most common endocrine disorders in dogs and is commonly proposed to be of autoimmune origin. Although the clinical presentation of human type 1 diabetes (T1D) and canine diabetes are similar, the aetiologies may differ. The aim of this study was to investigate if autoimmune aetiology resembling human T1D is as prevalent in dogs as previously reported. Sera from 121 diabetic dogs representing 40 different breeds were tested for islet cell antibodies (ICA) and GAD65 autoantibodies (GADA) and compared with sera from 133 healthy dogs. ICA was detected by indirect immunofluorescence using both canine and human frozen sections. GADA was detected by in vitro transcription and translation (ITT) of human and canine GAD65, followed by immune precipitation. Sections of pancreata from five diabetic dogs and two control dogs were examined histopathologically including immunostaining for insulin, glucagon, somatostatin and pancreas polypeptide. None of the canine sera analysed tested positive for ICA on sections of frozen canine or human ICA pancreas. However, serum from one diabetic dog was weakly positive in the canine GADA assay and serum from one healthy dog was weakly positive in the human GADA assay. Histopathology showed marked degenerative changes in endocrine islets, including vacuolisation and variable loss of immune-staining for insulin. No sign of inflammation was noted. Contrary to previous observations, based on results from tests for humoral autoreactivity towards islet proteins using four different assays, and histopathological examinations, we do not find any support for an islet autoimmune aetiology in canine diabetes mellitus.
Preventive Veterinary Medicine, 2005
The main objective of this study was to describe the incidence of mammary tumors (MTs) and the su... more The main objective of this study was to describe the incidence of mammary tumors (MTs) and the survival after MTs, in female dogs between 3 and 10 years of age (insured for veterinary care and with life insurance in a Swedish animal-insurance company) from 1995 to 2002. Measures of incidence are presented crudely, by breed and across age categories and birth cohorts (1991-1998). The survivals until MT diagnosis and after a MT diagnosis were computed. The overall incidence for any MT claim was 111 dogs per 10,000 dog-years at risk (DYAR). The overall MT rate in the 1992 and 1993 birth cohorts was 154 dogs per 10,000 DYAR. The incidence for any MT claim increased with age and varied by breed, from 319 dogs per 10,000 DYAR in the English springer spaniel to 5 dogs per 10,000 DYAR in the rough-haired collie. At the ages 6, 8 and 10 years, 1%, 6% and 13% respectively, of all www.elsevier.com/locate/prevetmed Preventive Veterinary Medicine 69 (2005) 109-127 * Corresponding author. Tel.: +46 18671369; fax: +46 18673545. E-mail addresses: agneta.egenvall@kv.slu.se, agneta.egenvall@kirmed.slu.se (A. Egenvall).
Journal of Veterinary Internal Medicine, 2004
Serum thymidine kinase (sTK) activity was evaluated as a tumor marker for canine malignant lympho... more Serum thymidine kinase (sTK) activity was evaluated as a tumor marker for canine malignant lymphoma (ML). The objective was to investigate if sTK, as in humans, could be used as a prognostic marker for survival time in dogs with ML and if sTK could identify early signs of progression of disease in treated dogs. Serum samples from 52 dogs with ML were tested for initial TK activity. Samples from 21 normal dogs and 25 dogs with nonhematologic neoplasms were used for comparison. Forty-four dogs with ML were treated. Serum TK activity was measured in treated dogs before each treatment and every 4 weeks thereafter until relapse. Dogs with ML had 2-180 times higher TK activity (TK 5-900 U/L) than normal dogs (TK &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;7 U/L) based on the mean + 2 standard deviations. In the group of other neoplasms, only 2 dogs had a moderate increase (6.4 and 7.5 U/L) compared with the controls. Mean sTK activities in the dogs with ML that had gone into complete remission (CR) were not significantly different from activities in healthy controls (P = .68). Mean sTK at least 3 weeks before and at the time of relapse was significantly higher than activity measured at CR (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .0001). Dogs with ML that initially had sTK &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;30 U/L had significantly shorter survival times (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .0001). Furthermore, sTK activity reflected the clinical staging of ML. Measuring sTK can be used as a powerful objective tumor marker for prognosis and for predicting relapse before recurrence of clinically detectable disease in dogs with ML undergoing chemotherapy.
Journal of Immunotherapy, 2008
Cutaneous canine melanomas are usually benign in contrast to human malignant melanoma. However, t... more Cutaneous canine melanomas are usually benign in contrast to human malignant melanoma. However, the canine oropharyngeal, uveal, and mucocutaneous neoplasms are aggressive and have metastatic potential. Surgery and to a lesser extent radiotherapy and chemotherapy are widely adopted treatments but are seldom curative in advanced stages. The similarities between human and canine melanoma make spontaneous canine melanoma an excellent disease model for exploring novel therapies. Herein, we report the first 2 adenovector CD40L immunogene (AdCD40L) treatments of aggressive canine malignant melanoma. Case no. 1 was an advanced stage III oral melanoma that was cured from malignant melanoma with 2 intratumor AdCD40L injections before cytoreductive surgery. After treatment, the tumor tissue was infiltrated with T lymphocytes and B lymphocytes suggesting immune activation. This dog survived 401 days after the first round of gene therapy and was free of melanoma at autopsy. Case no. 2 had a conjunctival malignant melanoma with a rapid progression. This case was treated with 6 AdCD40L injections over 60 days. One hundred and twenty days after start of gene therapy and 60 days after the last injection, the tumor had regressed dramatically, and the dog had a minimal tumor mass and no signs of progression or metastasis. Our results indicate that AdCD40L immunogene therapy is beneficial in canine malignant melanoma and could be considered for human malignant melanoma as well.
Electromagnetic Biology and Medicine, 1999
Many researchers have tried to explain the cause of damage to tumors exposed to electrochemical t... more Many researchers have tried to explain the cause of damage to tumors exposed to electrochemical treatment (ECT). In the present study, mammary tissue in adult female rats was treated with constant direct current to investigate the influence of current level, ...
Bioelectrochemistry, 2001
. Background: A reinvented technique for tumour therapy, electrochemical treatment EChT , is attr... more . Background: A reinvented technique for tumour therapy, electrochemical treatment EChT , is attracting increasing attention. This study compared results from treatment of liver and mammary tissue focusing on destruction and pH changes in the tissue close to the treatment electrodes. Subsequently, data were compared with a dose-planning model. Methods: Mammary or liver tissue in 50 adult Ž . female Sprague Dawley rats was given EChT with a constant, direct current. The electrodes used were PtrIr 9:1 with spherical tips. In situ pH measurements were taken with a micro-combination glass electrode. Results: Spherical lesions were produced in both liver and mammary tissue. No significant difference was detected when comparing the size of the lesions in the two kinds of tissue. Similar pH profiles were obtained in tissue surrounding the electrodes, with pH values changing rapidly from unphysiological to neutral status within the space of a few millimetres. The pH at the border of the macroscopic destruction zone, regardless of tissue type or coulomb dosage, Ž . correlated well with specific values 4.5-5.5 at the anode and between 9 and 10 at the cathode . Conclusion: The analogous destruction patterns in mammary and liver tissue support the hypothesis that EChT has similar results in at least these two different types of tissue. This implies that the destructive pattern caused by the treatment may be the same also in tumours. q
Bioelectrochemistry, 2002
Introduction: The aim of this study was to evaluate the cellular toxicity of different pH levels ... more Introduction: The aim of this study was to evaluate the cellular toxicity of different pH levels on the R3230AC mammary tumour cell line (clone-D) in vitro and to determine in what way the pH affects the tumour cells. The results could be used to interpret the cell damaging effects seen in electrochemical treatment of tumours (EChT), where pH alteration in tissue is the major event. Methods: Tumour cells were treated with pH 3.5, 5, 7, 9, 10 and 11 for 10, 20 or 30 min, respectively, followed by studies with the viability assay 3-(4,5-dimethylthiazol-2-yl)-2,5,-diphenyl tetrazolium bromide (methyltetrazolium (MTT)), morphological observation in phase contrast microscope (PCM) and light microscope, nucleotide analogue incorporation (BrdU; 5-Brdmo-2V -deoxyuridine), Caspase-3 activity measurement and detection of DNA fragmentation by an agarose gel electrophoresis. Results: In the viability assay, it was found that different pH levels had cytotoxic effects; these effects were dependent on the pH value and on the time of exposure at a given pH. Morphologically, cells in pH 3.5 and 5 had shrunk, were rounded and had condensed chromatin, whereas prominent cell swelling and nuclear expansion were seen in the pH 9-and 10treated cells. Gross cytolysis was found in pH 11. A BrdU incorporation assay indicated that proliferation rate is inhibited markedly both with decreasing and increasing pH. Significant Caspase-3 activity was found in pH 3.5 and 5 groups. Caspase-3 levels for the alkaline exposure were equal or below the normal control. DNA ladder formation, a characteristic of apoptosis, was only visualised in the treatment of pH 3.5 for 30 min. Conclusions: pH changes inhibit cell proliferation and decrease cell viability. The pathway of killing tumour cell in low pH probably has at least two directions: apoptosis and cell necrosis, whereas high pH results in only cell necrosis. The study suggests that low pH environment can induce apoptosis in unphysiological condition comparable with tissue pH at EChT. In addition, it seems that R3230AC mammary tumour cells are more tolerant to high pH than to acidic changes. This supports the theory that anodic EChT should be more efficient than cathodic. D
Bioelectrochemistry, 2003
Introduction: Electrochemical treatment (EChT) has been taken under serious consideration as bein... more Introduction: Electrochemical treatment (EChT) has been taken under serious consideration as being one of several techniques for local treatment of malignancies. The advantage of EChT is the minimal invasive approach and the absence of serious side effects. Macroscopic, histopathological and ultra-structural findings in liver following a four-electrode configuration (dog) and a two-electrode EChT design (dog and rat) were studied. Materials and methods: 30 female Sprague -Dawley rats and four female beagle dogs were studied with EChT using Platinum:Iridium electrodes and the delivered dose was 5, 10 or 90 C (As). After EChT, the animals were euthanized. Results: The distribution of the lesions was predictable, irrespective of dose and electrode configuration. Destruction volumes were found to fit into a logarithmic curve (dose -response). Histopathological examination confirmed a spherical (rat) and cylindrical/ellipsoidal (dog) lesion. The type of necrosis differed due to electrode polarity. Ultra-structural analysis showed distinct features of cell damage depending on the distance from the electrode. Histopathological and ultra-structural examination demonstrated that the liver tissue close to the border of the lesion displayed a normal morphology. Conclusions: The in vivo dose-planning model is reliable, even in species with larger tissue mass such as dogs. A multi-electrode EChT-design could obtain predictable lesions. The cellular toxicity following EChT is clearly identified and varies with the distance from the electrode and polarity. The distinct border between the lesion and normal tissue suggests that EChT in a clinical setting for the treatment of liver tumours can give a reliable destruction margin. D
Veterinary Record, 2008
Fifty-one dogs (27 diabetic dogs, four that had recovered from diabetes and 20 healthy control do... more Fifty-one dogs (27 diabetic dogs, four that had recovered from diabetes and 20 healthy control dogs) were given 0.5 or 1.0 mg glucagon intravenously. Blood samples were taken before the injection and 10 and 20 minutes after it. Samples were analysed to determine C-peptide, insulin and glucose concentrations, and one sample from each dog was analysed for fructosamine. The median (interquartile range) concentrations of C-peptide in the samples taken at 10 minutes were 0.5 (0.3 to 0.8) nmol/l in the control dogs, 0.1 (0 to 0.2) nmol/l in the diabetic dogs, and 0.3 (0.2 to 0.4) nmol/l in the dogs that had recovered from diabetes. Seven of the 51 dogs showed mild adverse reactions after the injection of glucagon.
International journal of oncology, 2009
Thymidine kinase 1 (TK), which is involved in the synthesis of DNA precursors, is only expressed ... more Thymidine kinase 1 (TK), which is involved in the synthesis of DNA precursors, is only expressed in S-G2 cells. Serum TK levels correlate to the proliferative activity of tumor disease. Determinations of TK levels have so far relied on radio enzyme assay (REA) and experimental ELISA methods, which have limited the clinical use of this biomarker, although recent studies in dogs with malignant lymphoma (ML) demonstrate its wide potential. A non-radiometric method based on a competitive immunoassay with specific anti-3'-azido-deoxythymidine monophosphate (AZTMP) antibodies has been further developed into the fully automated Liaison TK assay (DiaSorin). Sera from healthy dogs (n=30), and dogs with leukemia (LEUK) (n=35), ML (n=84), non-hematological tumors (n=50), and inflammatory disease (n=14) were tested using both methods. Lymphoma and LEUK samples were available before and during chemotherapy. The coefficients of variation for the Liaison TK assay in this study were 6.3 and 3.4...
Research in Veterinary Science, 2006
The aim of this study was to evaluate an enzyme-linked immunosorbent assay (ELISA), for determina... more The aim of this study was to evaluate an enzyme-linked immunosorbent assay (ELISA), for determination of serum thymidine kinase 1 (sTK1) activity in dogs with malignant lymphoma (ML) and compare it with a thymidine kinase (TK) radioenzymatic assay (TK-REA). The TK-REA has recently been shown to be useful in determining the clinical stage and prognosis in canine ML. In addition, serum lactate dehydrogenase (LDH) was measured. Forty-five dogs were included in the study. Sixty serum samples from these dogs, stored in a tumour serum sample bank (stored at -20 degrees C), were analysed. Apart from 37 dogs with ML, four normal dogs as well as two dogs with mammary carcinomas, one dog with bladder carcinoma, and one dog with malignant fibrous histiocytoma were included. Staging of ML was based on the modified World Health Organization (WHO) staging system for canine ML. The diagnosis of all tumours was verified by histopathology. The TK activity (units per litre [U/L]) ranged from 1.0 to 607.9 in the TK-REA analysis and from 1.1 to 510 in the TK-ELISA (normal reference value <7U/L). The range for LDH was between 12 and 1194 U/L (normal reference value <228 U/L). There was a significant correlation between the TK-REA and the TK-ELISA. The correlation coefficient (CC) was 0.97 and the standard error of the estimate (SEE) was 3.7 U/L. There was no correlation between LDH and either the TK-REA or the TK-ELISA (CC=0.53 for both assays; SEE=26.7 and 12.7 U/L, respectively). Most of the variation in LDH was still within the normal reference range. The mean LDH in dogs with high-stage (stage IV+V) disease was 201.9 U/L. The corresponding values for the TK-REA and TK-ELISA were 109 and 109.9 U/L, respectively. The significant relation between the TK-REA and the TK-ELISA was confirmed by Bland-Altman analysis. The TK-ELISA assay, because of its relative simplicity, will permit measurement of TK in cases of ML in dogs to become a routine procedure. PMID: 16140350 [PubMed -indexed for MEDLINE] J :595-6. Serum thymidine kinase (sTK) activity was evaluated as a tumor marker for canine malignant lymphoma (ML). The objective was to investigate if sTK, as in humans, could be used as a prognostic marker for survival time in dogs with ML and if sTK could identify early signs of progression of disease in treated dogs. Serum samples from 52 dogs with ML were tested for initial TK activity. Samples from 21 normal dogs and 25 dogs with nonhematologic neoplasms were used for comparison. Forty-four dogs with ML were treated. Serum TK activity was measured in treated dogs before each treatment and every 4 weeks thereafter until relapse. Dogs with ML had 2-180 times higher TK activity (TK 5-900 U/L) than normal dogs (TK <7 U/L) based on the mean + 2 standard deviations. In the group of other neoplasms, only 2 dogs had a moderate increase (6.4 and 7.5 U/L) compared with the controls. Mean sTK activities in the dogs with ML that had gone into complete remission (CR) were not significantly different from activities in healthy controls (P = .68). Mean sTK at least 3 weeks before and at the time of relapse was significantly higher than activity measured at CR (P < .0001). Dogs with ML that initially had sTK >30 U/L had significantly shorter survival times (P < .0001). Furthermore, sTK activity reflected the clinical staging of ML. Measuring sTK can be used as a powerful objective tumor marker for prognosis and for predicting relapse before recurrence of clinically detectable disease in dogs with ML undergoing chemotherapy. PMID: 15515587 [PubMed -indexed for MEDLINE] Abstract:Thymidine kinase 1 (TK), which is involved in the synthesis of DNA precursors, is only expressed in S-G2 cells.
International Journal of Molecular Medicine, 2005
Heterogeneous gene expression in tumours and the degradation of RNA when sampling under non-RNAse... more Heterogeneous gene expression in tumours and the degradation of RNA when sampling under non-RNAse-free conditions may limit the potential benefit of cDNA array studies. This study examines changes in the integrity of RNA by means of RNA gel electrophoresis at various post-operative intervals on canine mammary tumours (n=10) and malignant lymphoma (n=1). The tumours were cut into pieces (3-5 mm diameter, approximately 50 mg) and kept in tubes without RNAse-free buffer at room temperature. No special precautions were taken to avoid the influences of Rnase; rather, normal surgical procedures were used. We found that total RNA of the mammary tumours started to degrade within 30 min of the operation, and the rate of degradation increased up to 4 h, which was the last time point included in this study. RNA in the lymphoma tumours degraded more rapidly, and was completely degraded at 30 min post-operation. The degradation of mRNA in the mammary tumours, as studied by human cDNA arrays, was heterogeneous, i.e. some mRNA degraded completely, some only partially. This indicates that the mRNA degradation rate varied depending on the type of mRNA. However, since we found that gene expression differs depending on the part of the mammary tumour examined, one cannot exclude that the variation in the mRNA degradation rate may simply reflect heterogeneous gene expression within the tumour. We conclude that RNA integrity is unaffected immediately after sampling under non-RNAse-free conditions; however, the tumour sample should be preserved under RNAse-free conditions within 15 min to avoid RNA degradation. This is a much shorter time interval than previously reported in other similar studies; however, these studies generally treated normal tissue, under which 3-5 h non-RNAse-free conditions have been found not to affect RNA quality.
PLoS ONE, 2014
Diabetes mellitus is one of the most common endocrine disorders in dogs and is commonly proposed ... more Diabetes mellitus is one of the most common endocrine disorders in dogs and is commonly proposed to be of autoimmune origin. Although the clinical presentation of human type 1 diabetes (T1D) and canine diabetes are similar, the aetiologies may differ. The aim of this study was to investigate if autoimmune aetiology resembling human T1D is as prevalent in dogs as previously reported. Sera from 121 diabetic dogs representing 40 different breeds were tested for islet cell antibodies (ICA) and GAD65 autoantibodies (GADA) and compared with sera from 133 healthy dogs. ICA was detected by indirect immunofluorescence using both canine and human frozen sections. GADA was detected by in vitro transcription and translation (ITT) of human and canine GAD65, followed by immune precipitation. Sections of pancreata from five diabetic dogs and two control dogs were examined histopathologically including immunostaining for insulin, glucagon, somatostatin and pancreas polypeptide. None of the canine sera analysed tested positive for ICA on sections of frozen canine or human ICA pancreas. However, serum from one diabetic dog was weakly positive in the canine GADA assay and serum from one healthy dog was weakly positive in the human GADA assay. Histopathology showed marked degenerative changes in endocrine islets, including vacuolisation and variable loss of immune-staining for insulin. No sign of inflammation was noted. Contrary to previous observations, based on results from tests for humoral autoreactivity towards islet proteins using four different assays, and histopathological examinations, we do not find any support for an islet autoimmune aetiology in canine diabetes mellitus.
Preventive Veterinary Medicine, 2005
The main objective of this study was to describe the incidence of mammary tumors (MTs) and the su... more The main objective of this study was to describe the incidence of mammary tumors (MTs) and the survival after MTs, in female dogs between 3 and 10 years of age (insured for veterinary care and with life insurance in a Swedish animal-insurance company) from 1995 to 2002. Measures of incidence are presented crudely, by breed and across age categories and birth cohorts (1991-1998). The survivals until MT diagnosis and after a MT diagnosis were computed. The overall incidence for any MT claim was 111 dogs per 10,000 dog-years at risk (DYAR). The overall MT rate in the 1992 and 1993 birth cohorts was 154 dogs per 10,000 DYAR. The incidence for any MT claim increased with age and varied by breed, from 319 dogs per 10,000 DYAR in the English springer spaniel to 5 dogs per 10,000 DYAR in the rough-haired collie. At the ages 6, 8 and 10 years, 1%, 6% and 13% respectively, of all www.elsevier.com/locate/prevetmed Preventive Veterinary Medicine 69 (2005) 109-127 * Corresponding author. Tel.: +46 18671369; fax: +46 18673545. E-mail addresses: agneta.egenvall@kv.slu.se, agneta.egenvall@kirmed.slu.se (A. Egenvall).
Journal of Veterinary Internal Medicine, 2004
Serum thymidine kinase (sTK) activity was evaluated as a tumor marker for canine malignant lympho... more Serum thymidine kinase (sTK) activity was evaluated as a tumor marker for canine malignant lymphoma (ML). The objective was to investigate if sTK, as in humans, could be used as a prognostic marker for survival time in dogs with ML and if sTK could identify early signs of progression of disease in treated dogs. Serum samples from 52 dogs with ML were tested for initial TK activity. Samples from 21 normal dogs and 25 dogs with nonhematologic neoplasms were used for comparison. Forty-four dogs with ML were treated. Serum TK activity was measured in treated dogs before each treatment and every 4 weeks thereafter until relapse. Dogs with ML had 2-180 times higher TK activity (TK 5-900 U/L) than normal dogs (TK &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;7 U/L) based on the mean + 2 standard deviations. In the group of other neoplasms, only 2 dogs had a moderate increase (6.4 and 7.5 U/L) compared with the controls. Mean sTK activities in the dogs with ML that had gone into complete remission (CR) were not significantly different from activities in healthy controls (P = .68). Mean sTK at least 3 weeks before and at the time of relapse was significantly higher than activity measured at CR (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .0001). Dogs with ML that initially had sTK &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;30 U/L had significantly shorter survival times (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .0001). Furthermore, sTK activity reflected the clinical staging of ML. Measuring sTK can be used as a powerful objective tumor marker for prognosis and for predicting relapse before recurrence of clinically detectable disease in dogs with ML undergoing chemotherapy.
Journal of Immunotherapy, 2008
Cutaneous canine melanomas are usually benign in contrast to human malignant melanoma. However, t... more Cutaneous canine melanomas are usually benign in contrast to human malignant melanoma. However, the canine oropharyngeal, uveal, and mucocutaneous neoplasms are aggressive and have metastatic potential. Surgery and to a lesser extent radiotherapy and chemotherapy are widely adopted treatments but are seldom curative in advanced stages. The similarities between human and canine melanoma make spontaneous canine melanoma an excellent disease model for exploring novel therapies. Herein, we report the first 2 adenovector CD40L immunogene (AdCD40L) treatments of aggressive canine malignant melanoma. Case no. 1 was an advanced stage III oral melanoma that was cured from malignant melanoma with 2 intratumor AdCD40L injections before cytoreductive surgery. After treatment, the tumor tissue was infiltrated with T lymphocytes and B lymphocytes suggesting immune activation. This dog survived 401 days after the first round of gene therapy and was free of melanoma at autopsy. Case no. 2 had a conjunctival malignant melanoma with a rapid progression. This case was treated with 6 AdCD40L injections over 60 days. One hundred and twenty days after start of gene therapy and 60 days after the last injection, the tumor had regressed dramatically, and the dog had a minimal tumor mass and no signs of progression or metastasis. Our results indicate that AdCD40L immunogene therapy is beneficial in canine malignant melanoma and could be considered for human malignant melanoma as well.
Electromagnetic Biology and Medicine, 1999
Many researchers have tried to explain the cause of damage to tumors exposed to electrochemical t... more Many researchers have tried to explain the cause of damage to tumors exposed to electrochemical treatment (ECT). In the present study, mammary tissue in adult female rats was treated with constant direct current to investigate the influence of current level, ...
Bioelectrochemistry, 2001
. Background: A reinvented technique for tumour therapy, electrochemical treatment EChT , is attr... more . Background: A reinvented technique for tumour therapy, electrochemical treatment EChT , is attracting increasing attention. This study compared results from treatment of liver and mammary tissue focusing on destruction and pH changes in the tissue close to the treatment electrodes. Subsequently, data were compared with a dose-planning model. Methods: Mammary or liver tissue in 50 adult Ž . female Sprague Dawley rats was given EChT with a constant, direct current. The electrodes used were PtrIr 9:1 with spherical tips. In situ pH measurements were taken with a micro-combination glass electrode. Results: Spherical lesions were produced in both liver and mammary tissue. No significant difference was detected when comparing the size of the lesions in the two kinds of tissue. Similar pH profiles were obtained in tissue surrounding the electrodes, with pH values changing rapidly from unphysiological to neutral status within the space of a few millimetres. The pH at the border of the macroscopic destruction zone, regardless of tissue type or coulomb dosage, Ž . correlated well with specific values 4.5-5.5 at the anode and between 9 and 10 at the cathode . Conclusion: The analogous destruction patterns in mammary and liver tissue support the hypothesis that EChT has similar results in at least these two different types of tissue. This implies that the destructive pattern caused by the treatment may be the same also in tumours. q
Bioelectrochemistry, 2002
Introduction: The aim of this study was to evaluate the cellular toxicity of different pH levels ... more Introduction: The aim of this study was to evaluate the cellular toxicity of different pH levels on the R3230AC mammary tumour cell line (clone-D) in vitro and to determine in what way the pH affects the tumour cells. The results could be used to interpret the cell damaging effects seen in electrochemical treatment of tumours (EChT), where pH alteration in tissue is the major event. Methods: Tumour cells were treated with pH 3.5, 5, 7, 9, 10 and 11 for 10, 20 or 30 min, respectively, followed by studies with the viability assay 3-(4,5-dimethylthiazol-2-yl)-2,5,-diphenyl tetrazolium bromide (methyltetrazolium (MTT)), morphological observation in phase contrast microscope (PCM) and light microscope, nucleotide analogue incorporation (BrdU; 5-Brdmo-2V -deoxyuridine), Caspase-3 activity measurement and detection of DNA fragmentation by an agarose gel electrophoresis. Results: In the viability assay, it was found that different pH levels had cytotoxic effects; these effects were dependent on the pH value and on the time of exposure at a given pH. Morphologically, cells in pH 3.5 and 5 had shrunk, were rounded and had condensed chromatin, whereas prominent cell swelling and nuclear expansion were seen in the pH 9-and 10treated cells. Gross cytolysis was found in pH 11. A BrdU incorporation assay indicated that proliferation rate is inhibited markedly both with decreasing and increasing pH. Significant Caspase-3 activity was found in pH 3.5 and 5 groups. Caspase-3 levels for the alkaline exposure were equal or below the normal control. DNA ladder formation, a characteristic of apoptosis, was only visualised in the treatment of pH 3.5 for 30 min. Conclusions: pH changes inhibit cell proliferation and decrease cell viability. The pathway of killing tumour cell in low pH probably has at least two directions: apoptosis and cell necrosis, whereas high pH results in only cell necrosis. The study suggests that low pH environment can induce apoptosis in unphysiological condition comparable with tissue pH at EChT. In addition, it seems that R3230AC mammary tumour cells are more tolerant to high pH than to acidic changes. This supports the theory that anodic EChT should be more efficient than cathodic. D
Bioelectrochemistry, 2003
Introduction: Electrochemical treatment (EChT) has been taken under serious consideration as bein... more Introduction: Electrochemical treatment (EChT) has been taken under serious consideration as being one of several techniques for local treatment of malignancies. The advantage of EChT is the minimal invasive approach and the absence of serious side effects. Macroscopic, histopathological and ultra-structural findings in liver following a four-electrode configuration (dog) and a two-electrode EChT design (dog and rat) were studied. Materials and methods: 30 female Sprague -Dawley rats and four female beagle dogs were studied with EChT using Platinum:Iridium electrodes and the delivered dose was 5, 10 or 90 C (As). After EChT, the animals were euthanized. Results: The distribution of the lesions was predictable, irrespective of dose and electrode configuration. Destruction volumes were found to fit into a logarithmic curve (dose -response). Histopathological examination confirmed a spherical (rat) and cylindrical/ellipsoidal (dog) lesion. The type of necrosis differed due to electrode polarity. Ultra-structural analysis showed distinct features of cell damage depending on the distance from the electrode. Histopathological and ultra-structural examination demonstrated that the liver tissue close to the border of the lesion displayed a normal morphology. Conclusions: The in vivo dose-planning model is reliable, even in species with larger tissue mass such as dogs. A multi-electrode EChT-design could obtain predictable lesions. The cellular toxicity following EChT is clearly identified and varies with the distance from the electrode and polarity. The distinct border between the lesion and normal tissue suggests that EChT in a clinical setting for the treatment of liver tumours can give a reliable destruction margin. D
Veterinary Record, 2008
Fifty-one dogs (27 diabetic dogs, four that had recovered from diabetes and 20 healthy control do... more Fifty-one dogs (27 diabetic dogs, four that had recovered from diabetes and 20 healthy control dogs) were given 0.5 or 1.0 mg glucagon intravenously. Blood samples were taken before the injection and 10 and 20 minutes after it. Samples were analysed to determine C-peptide, insulin and glucose concentrations, and one sample from each dog was analysed for fructosamine. The median (interquartile range) concentrations of C-peptide in the samples taken at 10 minutes were 0.5 (0.3 to 0.8) nmol/l in the control dogs, 0.1 (0 to 0.2) nmol/l in the diabetic dogs, and 0.3 (0.2 to 0.4) nmol/l in the dogs that had recovered from diabetes. Seven of the 51 dogs showed mild adverse reactions after the injection of glucagon.