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G R Rutteman

Publications and source records attributed to G R Rutteman.

At least 19 recordsLinked to original sources
PubMed2006

Detection of lymph node micrometastases in malignant mammary tumours in dogs by cytokeratin immunostaining.

A series of 131 local and regional lymph nodes from 40 dogs with malignant mammary tumours were evaluated by staining with haematoxylin and eosin and immunohistochemically for antibodies to pancytokeratin (AE1/AE3) and cytokeratin 14. The immunohistochemical tests detected occult micrometastases in 9.2 per cent of the lymph nodes that were negative by haematoxylin and eosin staining. Under the modified TNM classification of canine mammary tumours, these results raised the clinical stage of 12.5 per cent of the affected dogs. However, if the latest TNM classification of human breast cancer had been applied, none of the animals would have been reclassified.

Animals↗
PubMed2006

E-cadherin expression in canine malignant mammary tumours: relationship to other clinico-pathological variables.

The relationship between E-cadherin epithelial expression, as detected by immunohistochemical methods, and other clinico-pathological characteristics of canine malignant mammary tumours was studied in 77 tumours surgically removed from 45 female dogs. The immunohistochemical assessment was based on the estimated percentage of epithelial cells with membranous labelling. Reduction of E-cadherin expression was significantly related to size and ulceration of tumours but not to fixation to skin or underlying tissue; it was also related to lymph node metastasis, necrosis and infiltrative growth. Histological type (but not histological grade) was related to E-cadherin expression, with solid tumours more frequently lacking expression and tubulopapillary tumours showing increased expression as compared with the other types. The significant relationship between E-cadherin and other known factors of poor prognosis suggests that the loss of E-cadherin expression may have prognostic value in canine malignant mammary tumours.

Animals↗
PubMed2006

Telomerase reverse transcriptase (TERT) expression and proliferation in canine brain tumours.

Telomerase is a ribonucleoprotein enzyme complex that synthesizes telomere DNA. It is detected in 85-90% of malignant tumours in humans, but not in most somatic cells. Because telomerase plays a critical role in cell immortality, it represents an important target for anticancer therapies. We have previously shown that the dog is a potentially useful model for evaluating telomerase-based therapeutics. In this present study we analysed 93 canine brain tumours for telomerase reverse transcriptase (TERT) expression by immunohistochemistry. TERT immunoreactivity was detected in 16 of 50 grade 1 (32%) and 29 of 43 grade 2 tumours (67.4%), demonstrating a statistically significant association with histological grade (P = 0.00012). A subset of 51 tumours was also assessed for MIB-1 expression. The MIB-1 labelling index (LI) was found to correlate significantly with tumour grade, with a mean MIB-1 LI of 1.5% for grade 1 tumours, as compared with a mean MIB-1 LI of 21.7% for grade 2 tumours (P << 0.001). The MIB-1 LI was also significantly associated with TERT expression in all brain tumours (P << 0.001). These data further support the dog as a model for the preclinical development of telomerase-based therapeutics in brain tumours.

Animals↗
PubMed2003

Study of dog and cat owners' perceptions of medical treatment for cancer.

Between April 10 and June 9, 2000, 91 owners of cats and dogs that were being or had been treated with anticancer chemotherapy were given a questionnaire designed to obtain information about their experiences as a result of the discovery and treatment of the disease, the efficacy and side effects of the treatment and their perceptions of the procedures associated with the administration of the drugs. Nearly all of the owners felt that the treatment was worthwhile. The level of observed side effects was low. Well over half of the owners believed that their animal had lived longer than it would have if it had not been treated and that its general wellbeing had improved. In general, they felt that the treatment had been rewarding and that any adverse side effects had been outweighed by the positive experiences during the treatment; they felt that they had been well informed and that their animals had benefited from the treatment.

Animals↗
PubMed2003

Validation of the use of proliferation markers in canine neoplastic and non-neoplastic tissues: comparison of KI-67 and proliferating cell nuclear antigen (PCNA) expression versus in vivo bromodeoxyuridine labelling by immunohistochemistry.

In order to evaluate the suitability of Ki-67 and proliferating cell nuclear antigen (PCNA) for determination of proliferative activity, the immunohistochemically determined nuclear expression of these antigens in canine non-neoplastic and neoplastic tissues was compared with the results of in vivo bromodeoxyuridine (BrdU) labelling, which - by measurement of the fraction of S-phase cells - is considered as the standard in the analysis of proliferative activity. The samples investigated consisted of non-neoplastic mammary and lymphoid tissues, and of benign and malignant (primary/metastatic) mammary tumours, and malignant lymphomas. Great regional heterogeneity prevented determination of an overall labelling index (LI) in normal lymphoid tissues. In the remaining combined group of samples, LI values were significantly ranked in the order PCNA>Ki-67>BrdU. However, the correlation of Ki-67 or PCNA as compared to BrdU LI values was only moderate in the combined group [approximately 0.5, Spearman rank test] as well as in most subgroups, whilst it was very poor in the group of primary mammary cancers. These observations indicate that Ki-67 or PCNA LIs as markers of proliferation do not evenly match in vivo BrdU labelling.

Animals↗
PubMed2002

Prognostic significance of a new histologic grading system for canine osteosarcoma.

Histologic grade is an important determinant in clinical outcome of human osteosarcoma (OS). In this study, the histologic characteristics of primary and metastatic canine OS were evaluated using a new classification system. Histologic characteristics were classified in 166 primary and 34 metastatic canine OS. Prognostic variables for clinical outcome were determined using multivariate analysis. Most OS were histologically characterized by severe to extreme cellular pleomorphism, a variable number of mitoses, small to moderate amounts of matrix, a high percentage of tumor cells, and minimal to moderate amounts of necrosis. Tumor invasion into vessels was present in 117/152 (71%) tumors, and 12/50 (24%) of the regional lymph nodes had evidence of metastasis. Classification of the 166 tumors resulted in seven (4%) grade 1, 34 (21%) grade II, and 125 (75%) grade III OS. In the multivariate analysis, histologic grade III OS and elevated pretreatment plasma alkaline phosphatase (AP) levels were independent predictors of clinical outcome. Dogs with high-grade tumors and elevated AP should be carefully evaluated for the presence of metastatic disease before starting adjunctive therapy protocols.

Animals↗
PubMed2001

Analysis of p53 mutational events and MDM2 amplification in canine soft-tissue sarcomas.

Canine cancer is of major significance in terms of animal health and welfare and soft tissue sarcomas are an important group of tumours accounting for approximately 15% of all canine tumours presented. Abnormal p53 protein expression and gene mutations have been identified in a number of different canine tumour types. However, mdm2 gene amplification has only been investigated in a limited number of canine osteosarcomas. In this present study a series of canine soft-tissue sarcomas (STS) were examined for p53 mutations and/or mdm2 amplification. For p53 mutational studies polymerase chain reaction and direct DNA sequencing was used. Gene mutations were identified in 6 of 30 (20%) primary tumour cases including MPNST (n=3) leiomysarcoma (n=1), heamangiosarcoma (n=1) and sarcoma (n=1). mdm2 gene amplification was assessed by Southern Blot. Although there was no evidence for major gene rearrangements, gene amplification was detected in 4 of 35 (11.4 %) primary tumours including MPNST (n=2), rhabdomyosarcoma (n=2). A total of 33 cases were examined for both p53 mutations and mdm2 amplification. Seven of the tumours were positive for p53 mutations, while five were positive for mdm2 amplification. With the exception of one case, a reciprocal relationship between the presence of a p53 mutation and mdm2 gene amplification was demonstrated.

Animals↗
PubMed2000

Cloning and cellular localization of the canine progesterone receptor: co-localization with growth hormone in the mammary gland.

The mammary gland has been found to express the gene encoding growth hormone (GH) in several species. Within the mammary gland, it may act as an autocrine/paracrine growth factor for cyclic epithelial changes, and may be a determinant in mammary carcinogenesis. In the dog, progestins enhance mammary GH expression. To elucidate the mechanism of progestin-induced mammary GH expression, the canine progesterone receptor (PR) is characterized and the cellular localization of the PR in normal and tumorous mammary tissues is examined. Sequence analysis of the canine PR revealed two in-frame ATG codons, encoding a putative PR-B protein of 939 amino acids and a putative PR-A protein of 765 amino acids. Western blot analysis indicated that both isoforms occur in uterus and mammary gland issues. Immunohistochemical analysis of the PR revealed that the PR was differentially expressed in mammary tissue, with many PR-positive epithelial cells in the proliferation phase of the glandular tissue and a low number of PR-positive cells in differentiated mammary tissue. Stromal and myoepithelial cells had no specific PR staining. Mammary tumours had a variety of staining patterns, including no staining, normal nuclear staining, marked heterogeneous immunoreactivity and perinuclear staining of tumorous epithelial cells and cytoplasmic-staining of spindle cells. Double staining showed that all GH-producing cells were positive for PR, whereas not all PR containing cells stained for GH. It is concluded that the activated PR may transactivate GH expression in the mammary gland within the same cell and functions as a pre-requisite transcription factor. However, during malignant transformation this regulation may be lost.

Amino Acid Sequence↗
PubMed1999

Stromal accumulation of chondroitin sulphate in mammary tumours of dogs.

To contribute to the investigation of the composition of the extracellular matrix in epithelial tumours, mammary gland tissues of dogs (including tumours, hyperplasias and normal tissue as well as metastatic lesions in lymph nodes and lung) were studied histochemically and immunohistochemically for distribution of sulphated glycosaminoglycans (s-GAGs). The formaline-fixed tissue was stained by alcian blue at pH 5.8, using the 'critical electrolyte concentration' to study the degree of sulphation of s-GAGs. s-GAGs were characterized by degradation with enzymes and nitrous acid and by immunohistochemistry with two anti-chondroitin sulphate monoclonal antibodies. The light microscopic investigation of s-GAG deposits revealed a limited number of patterns of their distribution. The main s-GAGs found in the mammary gland tumours of dogs and in metastatic lesions were chondroitin sulphate (CS) and heparin/heparan sulphate (HEP/HS). CS accumulated in diffuse structures between epithelial cells as well as around clusters of tumour cells. The latter pattern, possibly representing a mesenchymal reaction to the tumour, was present in 74% of the tumours, and in 67% of these, highly sulphated CS was present. A diffuse accumulation of CS was present almost exclusively in complex and mixed tumours; because of the expression of the 3B3 epitope for CS in immature cartilage the spindle cells of complex tumours are argued to be the precursors of the cartilage in mixed tumours. HEP/HS was stored mainly in mast cells that were found in increased numbers in hyperplasias and tumours. By pretreatment of microscopic slides with chondroitinase AC or ABC immunostaining of fibronectin could be made possible in areas in which CS was abundantly present, suggesting that CS may mask fibronectin epitopes. It is concluded that CS with different degrees of sulphation is the most important s-GAG in the extracellular matrix of mammary tumours of dogs. CS and other s-GAGs accumulate at different sites and may have a different pathogenetic significance.

Animals↗
PubMed1999

Evaluation of the results of a L-asparaginase-based continuous chemotherapy protocol versus a short doxorubicin-based induction chemotherapy protocol in dogs with malignant lymphoma.

The results of an L-asparaginase-based continuous chemotherapy protocol (n = 52) versus a short doxorubicin-based induction chemotherapy protocol (n = 65) were evaluated in 117 dogs with malignant lymphoma. There were no differences between the two groups in patient characteristics or incidence of protocol-related toxicity. Complete remission was induced in 71.2% of the dogs treated with the L-asparaginase protocol and in 67.7% of the dogs treated with the doxorubicin-plus protocol. The calculated Kaplan-Meier one- and two-year survival fractions in the L-asparaginase group were 48% and 26%, and in the doxorubicin-plus group 35%, and 22%, respectively. Differences in remission and survival between the two treatment groups were not significant. A multivariate Cox proportional hazards survival analysis revealed that elevated pretreatment plasma creatinine concentration and prior treatment with prednisolone were associated with shorter survival times. An elevated pretreatment plasma creatinine concentration and total leucocyte count were associated with a decrease in the disease-free period. Differences in efficacy and toxicity between the two protocols were not significant. There is no apparent advantage in using the continuous L-asparaginase protocol, and the shorter doxorubicin-plus protocol is less expensive and less time consuming.

Animals↗
PubMed1999

Expression and molecular characterization of the growth hormone receptor in canine mammary tissue and mammary tumors.

GH synthesis has been documented in canine mammary tissue and mammary tumors. In the present report, the characteristics of the GH receptor (GHR) are studied in these tissues. First, using immunohistochemistry, GHR was found to be present throughout normal and tumorous mammary tissues, being localized in epithelial and myoepithelial/spindle cell components and in the activated fibroblasts of desmoplastic tumor stroma. GHR expression seemed to be down-regulated only in terminally differentiated alveoli in normal tissue. GHR immunoreactivity in particular mammary (adeno)carcinomas was heterogenous. Second, the canine GHR was characterized at the molecular level. Northern blot analysis revealed a major GHR transcript of approximately 4.2 kb. The coding sequence of the canine GHR shows extensive homology with the GHR of several species. Seminested RT-PCR (using primers annealing in exons 4-5, exon 6, and exon 9) generated, next to the primary product, four different products in mammary tissues and the canine mammary tumor cell line CMT-U335, which seemed to be alternative GHR transcripts. These alternative GHR transcripts were characterized by exon 8 skipping, exon 7 skipping, and use of alternative splice donor and acceptor sites. Especially, the transcript that is missing exon 8 may encode a GH binding protein. In most malignant mammary samples, only the primary transcript was present; and alternative transcripts could not be detected. The absence of alternative GHR transcripts in mammary carcinomas, and thus putative inhibitors of GH-induced signal transduction, may contribute to enhanced sensitivity of malignant tumors to GH.

Alternative Splicing↗
PubMed1999

Lymphangiosarcomas in cats: a retrospective study of 12 cases.

Clinical, macroscopic, and histologic features of 12 lymphangiosarcomas in cats are described. Nine tumors were located in the subcutaneous tissue at the caudoventral abdominal wall (eight cats) or in the neck (one cat). The remaining three cats had lymphangiosarcomas around the cranial mesenteric artery (two cats) or precardial in the mediastinum (one cat). Macroscopically, the tumors were noncircumscribed, white, edematous, and intermixed with fat tissue. Histologic features varied from cleft-forming and cavernous growth to papilliform and solid patterns. Follow-up data were available for seven cats with subcutaneous lymphangiosarcomas. All these cats died or were euthanatized within 6 months after surgery because of poor wound healing, local recurrence, or distant metastases. The cats with abdominal or thoracic masses were either euthanatized at surgery or within 6 months after the first surgery because of recurrent chylothorax, chyloperitoneum, or distant metastases.

Abdominal Muscles↗
PubMed1998

Cobalt 60 irradiation of pituitary gland tumors in three cats with acromegaly.

Acromegaly was diagnosed in 3 cats with insulin-resistant diabetes mellitus (DM) on the basis of history and physical examination findings, which ruled out other causes of insulin-resistant DM, and by documenting high plasma concentrations of growth hormone. Computed tomography revealed a mass in the area of the pituitary gland in each cat. Pituitary gland tumors were irradiated with cobalt 60, and none of the cats developed complications to radiotherapy. Each cat received a total dose of 48 Gy of cobalt 60 during 12 treatments. After completion of radiotherapy, insulin requirements were less for all cats, although in 1 cat, this improvement was transient. Diabetes mellitus resolved in 2 of 3 cats. After treatment, decreases in insulin requirements correlated with decreases in plasma growth hormone concentrations in 2 of 3 cats in which DM resolved. On the basis of these findings, irradiation of pituitary gland tumors appears to be a treatment option for cats with acromegaly.

Acromegaly↗
PubMed1998

Genomic organization of the canine p53 gene and its mutational status in canine mammary neoplasia.

To determine whether canine malignancies share common genetic lesions with their human counterparts, and are thus potentially interesting model systems in which to pose questions regarding tumor etiology and progression, we have elucidated the entire exon/intron structure of the canine p53 gene. A search for p53 gene abnormalities in mammary tumor tissue was undertaken utilizing single strand conformation polymorphism analysis. Mutations were detected in exons 4, 5, 6, and 7 of the p53 gene and consisted of nonsense, splicing, and frameshift mutations. None of 11 benign tumors and 6 of 40 primary carcinomas (15%) were found to harbor subtle p53 mutations. In 14 carcinomas examined the results in primary tumors and metastases were the same. These findings implicate involvement of this gene in the genesis of some malignant canine tumors, in a fashion similar to their human counterparts.

Alleles↗
PubMed1998

Multi-agent chemotherapy for mast cell tumours in the dog.

Seventeen dogs with mast cell tumours received chemotherapy. Fifteen dogs were treated with a vincristine, cyclophosphamide, hydroxyurea, and prednisolone (VCHP) regimen. Seven of these were later switched to doxyrubicin and prednisolone either because they stopped responding or because they did not respond from the start of the treatment. Two dogs received the latter regimen as the primary therapy. All dogs were treated with cimitidine and metoclopramide to minimize the effect of paraneoplastic syndrome associated with histamine release. Ten of the 17 dogs were found to respond (4/17 complete response (CR), 6/17 partial response (PR)). Response duration varied from 39 to 910 days (median 53 days), including 3 dogs with a CR that lasted more than 2 years. Survival time in responders varied from 41 to 910 days (median 97 days) and from 30 to 126 (median 39) in the other 7 dogs. Dogs that became refractory to VCHP did not respond to doxyrubicin and prednisolone. It is concluded that multi-agent chemotherapy has anti-tumour activity in a considerable proportion of dogs with mast cell tumours, but its efficacy is variable. The multivariate analyses showed that significant factors predicting survival in dogs with mast cell tumours were sex (P = 0.009), absence or presence of non-abdominal distant metastases, or abdominal metastases, respectively (P = 0.023), and malignancy grade of the tumours (P = 0.053).

Animals↗
PubMed1998

Analysis of chromosome aberrations in a mammary carcinoma cell line from a dog by using canine painting probes.

A cell line derived from a spleen metastasis of a mammary carcinoma in a female dog was analyzed by fluorescence in situ hybridization with canine chromosome-specific paints. The cell line showed a modal chromosome number of 77, with three (90% of the cells) or four (10% of the cells) biarmed chromosomes. Aberrations observed relate to chromosomes 8 or 11, 13 or 15, 37, 38, and X and include chromosome loss (X), formation of isochromosomes (8 or 11, 13 or 15), and centric fusion (37 and 38). In all aberrations, whole chromosomes are involved. None of the genes known to be related to breast cancer development in humans and that has mapped in the dog is located on one of the aberrant chromosomes. The results of this study show that chromosome painting is a most useful tool for the analysis of canine tumor cells.

Animals↗