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Application of Omics Technology in Diagnosis of the Canine Cancers
2019
Zamani-Ahmadmahmudi, Mohamad | azizi, Shahrzad
Nowadays, with the development of new technologies, improved and progressed methods have been taken to diagnose, treat and prevent cancers. Pathologic study and some molecular methods have been helpful in diagnosing and predicting cancer but these methods are not enough in many cases. Omics technology investigates many parts of cells such as genes, proteins, transcripts, and metabolites simultaneously. This procedure provides a more real and general feature of cellular processes, especially in cancer cells. In human, Omics technology is widely used to diagnose and treat various cancers and predict prognosis of tumors and survival of patients. In parallel to the studies of cancers in human, similar investigations were conducted in the canine cancers. Regarding the importance of Omics method in oncology, we described various Omics techniques including genomics, transcriptomics, and proteoimcs. In addition, corresponding studies carried out in different canine cancers were summarized in the next step.
Afficher plus [+] Moins [-]In vitro drug sensitivity in canine lymphoma
2016
Introduction: Due to the high heterogeneity of canine lymphoma, the aim of the present study was to test in vitro the chemosensitivity of canine high-grade primary lymphoma cells to various cytostatic drugs commonly used to treat dogs: 4-HO-cyclophosphamide, doxorubicin, dexamethasone, prednisolone, vincristine, etoposide, chlorambucil, lomustine, and cytosine arabinoside. Material and Methods: To determine the cell viability and drug ability to induce apoptosis two different tests were used: an MTT assay and annexin V/propidium iodide staining. Results: Both in vitro tests were found to be useful tools. Significant differences in the sensitivity, depending on the drug type, between B-, T- and mixed/null-type lymphoma cells were found for the majority of the tested drugs. B-type cells were the most sensitive in vitro, whereas T-type cells seemed to be the most resistant. Doxorubicin, chlorambucil, etoposide, and vincristine most strongly reduced the cell viability and induced apoptosis. Conclusion: In vitro assays, such as the MTT test and especially the annexin V/PI assay, may be useful tools for predicting a response to the treatment of high-grade lymphoma in dogs or improving the treatment outcomes in individual animals.
Afficher plus [+] Moins [-]DIAGNOSIS AND MANAGEMENT OF LYMPHOMA IN A GERMAN SHEPERD DOG : A CASE REPORT
2024
G.R. Baranidharan | Rajat Sagare | C. Jayanthy | A. Gopalakrishnan | S. Abinaya | Ashi Krishna
A case was diagnosed as canine multicentric lymphoma based on clinical presentation, FNAC and ultrasonography and was treated with CHOP-19 protocol and remission was observed on 9th week but the protocol was continued up to 19th week and no signs of relapse was noticed. The animal was monitored every month for month after the treatment (19 weeks) animal showed no signs of reoccurrence up to 7 months. Multicentric lymphoma is a disease that the general practitioner can manage; it does not require referral to a specialized practice.
Afficher plus [+] Moins [-]Anticancer effect of metformin alone and in combination with 2-deoxy-D-glucose on mouse T cell lymphoma EL4 cells
2023
Kim, S.Y. | Joo, H.G.
Metformin is a treatment used widely for non-insulin-dependent diabetes mellitus with few side effects and acts by inhibiting hepatic gluconeogenesis and glucose absorption from the gastrointestinal tract. Lymphoma is one of the most common hematological malignancies in dogs. Chemotherapy is used mainly on lymphoma, but further research on developing anticancer drugs for lymphoma is needed because of its severe side effects. This study examined the anticancer effects of metformin alone and in combination with 2-deoxy-D-glucose (2-DG), a glucose analog, on EL4 cells (mouse T cell lymphoma). Metformin reduced the metabolic activity of EL4 cells and showed an additive effect when combined with 2-DG. In addition, cell death was confirmed using a trypan blue exclusion test, Hochest 33342/propidium iodide (PI) staining, and Annexin V/PI staining. An analysis of the cell cycle and mitochondria membrane potential (MMP) to investigate the mechanism of action showed that metformin stopped the G2/M phase of EL4 cells, and metformin + 2-DG decreased MMP. Metformin exhibited anticancer effects as a G2/M phase arrest mechanism in EL4 cells and showed additive effects when combined with 2-DG via MMP reduction. Unlike cytotoxic chemotherapeutic anticancer drugs, metformin and 2-DG are related to cellular glucose metabolism and have little toxicity. Therefore, metformin and 2-DG can be an alternative to reduce the toxicity caused by chemotherapeutic anticancer drugs. Nevertheless, research is needed to verify the in vivo efficacy of metformin and 2-DG before they can be used in lymphoma treatments.
Afficher plus [+] Moins [-]Peritoneal lymphomatosis with pleural and peritoneal effusions in a dog: a case report
2023
Kang, M.J. | Bae, H.A. | Jung, R.K. | Kim, M.J. | Cha, S.M. | Hwang, T.S. | Lee, H.C. | Jung, D.I. | Cho, K.W. | Yu, D.H.
Peritoneal lymphomatosis (PL) is a rare lymphoid neoplasm in dogs. A nine-yearold spayed female Labrador retriever presented with pleural and peritoneal effusions. Diagnostic imaging revealed diffuse nodular to massive lesions in the mesentery, particularly in the caudal abdomen. While the superficial lymph nodes did not show significant changes, enlargement was observed in the intra-abdominal and intra-thoracic lymph nodes. Cytological and flow cytometric analyses of the effusion indicated the presence of large B-cell lymphocytes expressing CD3⁻/CD5⁻/ CD14⁻/CD21⁻/CD34⁺/CD45⁺/CD79a⁺. PL was diagnosed using diagnostic imaging and fluid analysis. This case report highlights the clinical and diagnostic features of canine PL.
Afficher plus [+] Moins [-]A retrospective study of 16 cats with intermediate- to high-grade alimentary lymphoma
2021
Kwak, D.H. | Cho, M.J. | Park, H.J. | Song, K.H. | Seo, K.W.
The purpose of this retrospective study was to describe cases of feline intermediate- to high-grade alimentary lymphoma regarding signalment, clinical presentation, laboratory findings, response to therapy (modified 25-week University of Wisconsin-Madison [UW-25] vs. COP [cyclophosphamide, vincristine, prednisone]), toxicosis, and outcomes and to identify prognostic factors. Sixteen cats were treated with chemotherapy protocols. Response rates and survival did not differ statistically between the two protocols. The progression-free interval (PFI) and median survival time (MST) in cats achieving a response to therapy were longer than in those with no response [NR] (complete remission [CR] vs. partial remission [PR] vs. NR; PFI, 124 vs. 49 vs. 12 days, p < 0.001; MST, 361 vs. 118 vs. 16 days, p < 0.001). Clinical stage was another prognostic factor for PFI and MST. The PFI and MST in cats in stage I were longer than in those in other stages (PFI, 107 days vs. 30 days; MST, 193 days vs. 54 days). Hematologic and gastrointestinal toxicosis was mostly low grade. In comparing the modified UW-25 protocol with the COP protocol, there was not much difference in the number of neutropenic episodes and grade levels.
Afficher plus [+] Moins [-]CD3+/CD4+/CD5+/CD8+/CD21+/CD34-/CD45-/CD79a-/TCRαβ+/TCRγδ-/MHCII+ T-zone lymphoma in a dog with generalized lymphadenopathy: a case report
2021
Shin, S.W. | Lim, Y.J. | Bae, H.A. | Kim, J.H. | Cho, A.R. | Park, J.H. | Lee, D.B. | Jung, D.I. | Kim, S.K. | Yu, D.H.
Canine T-zone lymphoma (TZL) is a mature T-cell lymphoma in dogs. The diagnosis and sub-classification are impossible without biopsy or immunophenotyping by flow cytometry. An 11-year-old, spayed, female Golden Retriever presented with lymph node enlargement. Clinical examination was consistent with canine multicentric lymphoma. However, immunophenotyping revealed positive for CD3, CD4, CD5, CD8, CD21, TCRαβ, and MHCII but negative for CD34, CD45, CD79a, and TCRγδ. Histopathology revealed lymphocytes expanding to the cortex-preserving architecture and thinning of the nodal capsule, and CD3 positive but PAX-5 negative. Owing to the indolent nature of TZL, careful monitoring approach without clinical intervention was utilized.
Afficher plus [+] Moins [-]Assessment of folate receptor expression and folate uptake in multicentric lymphomas in dogs
2014
Objective-To determine expression of folate receptors (FRs) and folate uptake in multicentric lymphomas in dogs. Sample-10 dogs with histopathologically confirmed multicentric lymphoma and 20 archival lymph node biopsy specimens from dogs with multicentric lymphoma. Procedures-Multicentric lymphomas in 10 dogs were prospectively evaluated for FR expression by use of immunohistochemical analysis and for in vivo folate uptake by use of nuclear scintigraphy. Dogs with FR-expressing tumors were eligible for FR-targeted chemotherapy. Twenty archival lymphoma biopsy specimens were also evaluated with immunohistochemical analysis. Results-FRs were not detected with immunohistochemical analysis in lymph node samples obtained from the 10 dogs or in archival biopsy specimens. However, nuclear scintigraphy revealed uptake of radioactive tracer in 6 of 10 dogs. Five of these 6 dogs were treated with an FR-targeted chemotherapeutic agent; results of treatment were complete remission in 1 dog, stable disease in 2 dogs, and progressive disease in 2 dogs. Treatment-related toxicoses generally were mild. Conclusions and Clinical Relevance-This study provided strong evidence for folate uptake in a substantial portion of multicentric lymphomas of dogs and indicated the antitumor activity of FR-targeted chemotherapeutics for these cancers. Use of FR-targeted chemotherapeutics may be promising for the treatment of FR-expressing multicentric lymphomas in dogs. Further studies are needed to determine reasons for lack of immunoreactivity to currently identified anti-FR antibodies and to develop improved methods for detecting FRs in lymphomas of dogs.
Afficher plus [+] Moins [-]Evaluation of vincristine-associated myelosuppression in Border Collies
2013
Lind, Denise L. | Fidel, Janean (Janean L) | Gay, John M. | Mealey, Katrina L.
Objective: To determine whether Border Collies (ATP binding cassette subfamily B1 gene [ABCB1] wildtype) were more likely than other breeds to develop vincristine-associated myelosuppression (VAM) and, if so, whether this was caused by a mutation in ABCB1 distinct from ABCB1-1Δ. Animals: Phase 1 comprised 36 dogs with the ABCB1 wildtype, including 26 dogs with lymphoma (5 Border Collies and 21 dogs representing 13 other breeds) treated with vincristine in a previous study; phase 2 comprised 10 additional Border Collies, including 3 that developed VAM and 7 with an unknown phenotype. Procedures: For phase 1, the prevalence of VAM in ABCB1-wildtype Border Collies was compared with that for ABCB1-wildtype dogs of other breeds with data from a previous study. For phase 2, additional Border Collies were included. Hematologic adverse reactions were graded with Veterinary Co-operative Oncology Group criteria. Genomic DNA was used to amplify and sequence all 27 exons of the canine ABCB1. Sequences from affected dogs were compared with those of unaffected dogs and dogs of unknown phenotype. Results: 3 of 5 Border Collies with the ABCB1 wildtype developed VAM; this was significantly higher than the proportion of other dogs that developed VAM (0/21). A causative mutation for VAM in Border Collies was not identified, although 8 single nucleotide polymorphisms in ABCB1 were detected. Conclusions and Clinical Relevance: Breed-associated sensitivity to vincristine unrelated to ABCB1 was detected in Border Collies. Veterinarians should be aware of this breed predisposition to VAM. Causes for this apparent breed-associated sensitivity should be explored.
Afficher plus [+] Moins [-]Evaluation of four methods used to measure plasma insulin-like growth factor 1 concentrations in healthy cats and cats with diabetes mellitus or other diseases
2012
Tschuor, Flurin | Zini, Eric | Schellenberg, Stefan | Wenger, Monique | Boretti, Felicitas S. | Reusch, Claudia E.
Objective: To evaluate 4 methods used to measure plasma insulin-like growth factor (IGF) 1 concentrations in healthy cats and cats with diabetes mellitus or other diseases. Animals: 39 healthy cats, 7 cats with diabetes mellitus, and 33 cats with other diseases. Procedures: 4 assays preceded by different sample preparation methods were evaluated, including acid chromatography followed by radioimmunoassay (AC-RIA), acid-ethanol extraction followed by immunoradiometry assay (AEE-IRMA), acidification followed by immunochemiluminescence assay (A-ICMA), and IGF-2 excess followed by RIA (IE-RIA). Validation of the methods included determination of precision, accuracy, and recovery. The concentration of IGF-1 was measured with all methods, and results were compared among cat groups. Results: The intra-assay coefficient of variation was < 10% for AC-RIA, A-ICMA, and AEE-IRMA and 14% to 22% for IE-RIA. The linearity of dilution was close to 1 for each method. Recovery rates ranged from 69% to 119%. Five healthy cats had IGF-1 concentrations > 1,000 ng/mLwith the AEE-IRMA, but < 1,000 ng/mL with the other methods. Compared with healthy cats, hyperthyroid cats had significantly higher concentrations of IGF-1 with the A-ICMA method, but lower concentrations with the IE-RIA method. Cats with lymphoma had lower IGF-1 concentrations than did healthy cats regardless of the method used. Conclusions and Clinical Relevance: Differences in the methodologies of assays for IGF-1 may explain, at least in part, the conflicting results previously reported in diabetic cats. Disorders such as hyperthyroidism and lymphoma affected IGF-1 concentrations, making interpretation of results more difficult if these conditions are present in cats with diabetes mellitus.
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