Gennaro Altamura, Manuela Martano, Anna Matrone, Annunziata Corteggio, Giuseppe Borzacchiello
{"title":"Monoclonal antibody cetuximab impairs matrix metalloproteinases 2 and 9, epithelial-mesenchymal transition and cell migration in feline oral squamous cell carcinoma in vitro.","authors":"Gennaro Altamura, Manuela Martano, Anna Matrone, Annunziata Corteggio, Giuseppe Borzacchiello","doi":"10.1111/vco.12943","DOIUrl":"10.1111/vco.12943","url":null,"abstract":"<p><p>Feline oral squamous cell carcinoma (FOSCC) is characterised by invasive and metastatic behaviour and is poorly responsive to current treatments, hence the need for new therapeutic strategies. FOSCC shares molecular targets with human head and neck squamous cell carcinoma (HNSCC), among these the epidermal growth factor receptor. Cetuximab is an anti-epidermal growth factor receptor monoclonal antibody employed in the therapy of HNSCC and, interestingly, previous work in vitro suggested that it displays cytostatic and cytotoxic properties also against FOSCC. With the present study, we aimed at further investigating the effects of cetuximab on invasion and metastasis pathways proven to be relevant in human patients. To this purpose, FOSCC cell lines SCCF1, SCCF2 and SCCF3 were treated with cetuximab for 48/72 h and subjected to Western blot for matrix metalloproteinases-2/9 (MMP-2/9) and epithelial-mesenchymal transition markers vimentin, E-, P- and N-cadherin. Treatment with cetuximab resulted in downregulation of MMP-2/-9 in all of the three cell lines in a dose-dependent manner. Moreover, cetuximab downregulated vimentin and P-cadherin in SCCF1, upregulated E-cadherin whilst downregulating P-/N-cadherins in SCCF2, and impaired P-/N-cadherins in SCCF3. An in vitro scratch test also demonstrated that cetuximab delayed cell migration in SCCF3. These data suggest that cetuximab mitigates invasion and metastasis processes by impairing MMPs and epithelial-mesenchymal transition pathways in FOSCC, indicating that this monoclonal antibody may help to counteract malignant progression and improve the management of locally invasive disease.</p>","PeriodicalId":23693,"journal":{"name":"Veterinary and comparative oncology","volume":" ","pages":"149-155"},"PeriodicalIF":2.1,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138463003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Silvia Sabattini, Vito Antonio Baldassarro, Riccardo Zaccone, Laura Calzà, Luciana Giardino, Marta Vascellari, Luca Lorenzini, Marzia Moretti, Laura Marconato
{"title":"Dysregulated miRNAs in a canine model of haemangiosarcoma metastatic to the brain.","authors":"Silvia Sabattini, Vito Antonio Baldassarro, Riccardo Zaccone, Laura Calzà, Luciana Giardino, Marta Vascellari, Luca Lorenzini, Marzia Moretti, Laura Marconato","doi":"10.1111/vco.12949","DOIUrl":"10.1111/vco.12949","url":null,"abstract":"<p><p>Haemangiosarcoma is a highly metastatic and lethal cancer of blood vessel-forming cells that commonly spreads to the brain in both humans and dogs. Dysregulations in phosphatase and tensin (PTEN) homologue have been identified in various types of cancers, including haemangiosarcoma. MicroRNAs (miRNAs) are short noncoding single-stranded RNA molecules that play a crucial role in regulating the gene expression. Some miRNAs can function as oncogenes or tumour suppressors, influencing important processes in cancer, such as angiogenesis. This study aimed to investigate whether miRNAs targeting PTEN were disrupted in canine haemangiosarcoma and its corresponding brain metastases (BM). The expression levels of miRNA-10b, miRNA-19b, miRNA-21, miRNA-141 and miRNA-494 were assessed in samples of primary canine cardiac haemangiosarcomas and their matched BM. Furthermore, the miRNA profile of the tumours was compared to samples of adjacent non-cancerous tissue and healthy control tissues. In primary cardiac haemangiosarcoma, miRNA-10b showed a significant increase in expression, while miRNA-494 and miRNA-141 exhibited downregulation. Moreover, the overexpression of miRNA-10b was retained in metastatic brain lesions. Healthy tissues demonstrated significantly different expression patterns compared to cancerous tissues. In particular, the expression of miRNA-10b was nearly undetectable in both control brain tissue and perimetastatic cerebral tissue. These findings can provide a rationale for the development of miRNA-based therapeutic strategies, aimed at selectively treating haemangiosarcoma.</p>","PeriodicalId":23693,"journal":{"name":"Veterinary and comparative oncology","volume":" ","pages":"70-77"},"PeriodicalIF":2.1,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138799869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chiara Agnoli, Sofia Rimondi, Giulia Ghisoni, Dina Guerra, Michele Tumbarello, Simone Perfetti, Alessandro Tirolo, Laura Marconato
{"title":"Spotlight on capecitabine for the treatment of unresectable or metastatic carcinoma of various origin: A retrospective study of 25 dogs.","authors":"Chiara Agnoli, Sofia Rimondi, Giulia Ghisoni, Dina Guerra, Michele Tumbarello, Simone Perfetti, Alessandro Tirolo, Laura Marconato","doi":"10.1111/vco.12945","DOIUrl":"10.1111/vco.12945","url":null,"abstract":"<p><p>Capecitabine, the oral prodrug of 5-fluorouracil, is indicated in people to treat various malignant epithelial cancers. In dogs, capecitabine has not been extensively evaluated. The aim of this retrospective study was to investigate toxicity and preliminary efficacy of single agent capecitabine in dogs with advanced malignant epithelial cancers of any site, for which no effective therapy existed, conventional treatment failed or was declined. Capecitabine was administered orally at 750 mg/m<sup>2</sup> from day 1 to 14, followed by 1-week rest period, given as 3-week cycles. Safety evaluation was performed after 2 cycles, and every 2-3 cycles thereafter. Tumour response was determined every 2-3 cycles. Twenty-five dogs with hepatocellular carcinoma (n = 6), lung papillary carcinoma (n = 4), anal sac adenocarcinoma (n = 3), colic adenocarcinoma (n = 2), and other individually represented epithelial cancers (n = 10) were included. Dogs received a median of 4 cycles (range, 2-43) for a median of 84 days (range, 42-913). Toxicity occurred in 17 (68.0%) dogs; the most frequent adverse events were gastrointestinal, with the majority being self-resolving and of mild grade. Of the 22 dogs with macroscopic disease, 3 (13.6%) achieved partial remission, 16 (72.7%) were stable and 3 (13.6%) progressed; overall clinical benefit rate was 86.4%. Median progression-free interval was 93 days (95% CI 42-154; range, 1-521) and median tumour-specific survival was 273 days (95% CI 116-482; range 45-913). These findings suggest that capecitabine is an attractive option for the treatment of several types of carcinomas in dogs. Prospective studies are warranted to optimize the scheduling of capecitabine and confirm its efficacy.</p>","PeriodicalId":23693,"journal":{"name":"Veterinary and comparative oncology","volume":" ","pages":"42-48"},"PeriodicalIF":2.1,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138463004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Treatment of feline intermediate to high-grade alimentary lymphoma: A retrospective evaluation of 55 cats treated with the VAPC combination chemotherapy protocol (2017-2021).","authors":"Antony Stewart Moore, Angela Erica Frimberger","doi":"10.1111/vco.12958","DOIUrl":"10.1111/vco.12958","url":null,"abstract":"<p><p>The most commonly utilized protocols to treat lymphoma in cats employ vincristine, cyclophosphamide and prednisone; with additional drugs sometimes used including L-asparaginase and doxorubicin. Medical records were reviewed for 55 cats with alimentary lymphoma treated with a novel multiagent protocol using prednisolone, L-asparaginase, doxorubicin, vinblastine instead of vincristine, a higher dosage of cyclophosphamide and oral procarbazine (VAPC protocol). Outcomes evaluated were response to therapy, toxicity and progression-free survival (PFS). Grade 3 or 4 neutropenia was the most common treatment-related reason for chemotherapy dosage adjustment, occurring in 8 of 52 cats receiving vinblastine, 7 of 55 cats receiving cyclophosphamide and 1 of 40 cats receiving doxorubicin, but febrile neutropenia was identified in only two cats. Of 38 cats receiving chemotherapy for measurable disease, 26 (68.4%) achieved complete response (CR). Three cats achieved a partial response and 9 cats failed to achieve a remission. There were no identified factors influencing whether a cat was likely to achieve CR. For all 55 cats (including those receiving chemotherapy and surgery), median PFS was 184 days with 1, 2 and 3-year survival rates of 35.4%, 26.5% and 26.5%, respectively. On multivariate analysis, 40 cats that achieved CR had a median survival time of 341 days (78 days for PR, 45 days for NR); PFS times were also significantly affected by lymphocyte:monocyte L:M ratio (>3.4 = 700 days vs. ≤3.4 = 126 days) and B-cell versus T-cell phenotype (220 days vs. 42 days, respectively).</p>","PeriodicalId":23693,"journal":{"name":"Veterinary and comparative oncology","volume":" ","pages":"106-114"},"PeriodicalIF":2.1,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139049393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Eleanor K Wyatt, Verena Affolter, Stefano Borio, Alexandra Guillen, Sara Verganti, Sue Murphy, Damiano Ballarini, Frane Banovic, Vanessa Schmidt, Jean-Benoit Tanis
{"title":"Mastocytosis in the skin in dogs: A multicentric case series.","authors":"Eleanor K Wyatt, Verena Affolter, Stefano Borio, Alexandra Guillen, Sara Verganti, Sue Murphy, Damiano Ballarini, Frane Banovic, Vanessa Schmidt, Jean-Benoit Tanis","doi":"10.1111/vco.12962","DOIUrl":"10.1111/vco.12962","url":null,"abstract":"<p><p>Canine cutaneous mastocytosis (CM) is rare in contrast to canine mast cell tumours. In humans, CM commonly affects children and is usually indolent with possible spontaneous resolution. Systemic mastocytosis (SM) with bone marrow involvement typically affects adults, can have a poor outcome, and often includes skin lesions. 'Mastocytosis in the skin' (MIS) is the preferred term of skin lesions, if bone marrow evaluations are not available, which is often the cases in dogs. In human SM and CM, KIT mutations are often detected. The veterinary literature suggests clinical resemblances between human and canine MIS, but data is limited, and KIT mutations are rarely assessed. This retrospective study describes clinicopathological findings, treatment and outcome of 11 dogs with suspected MIS. Dogs with multiple mast cell tumours were excluded. Histopathology reports (n = 5) or slides (n = 6) were reviewed. KIT mutation analysis including exons 8, 9, 11, 14 and 17 were analysed in eight dogs. Median age at diagnosis was 4 years (range, 1-12). Typical clinical signs included multifocal to generalised nodules and papules. Histologically, skin lesions were characterised by dermal infiltration of well-differentiated mast cells. KIT mutations were detected in 3/8 dogs (exon 9: n = 2; exon 11: n = 1). One dog had mastocytaemia suggesting possible SM. Glucocorticoids were mostly successful with lesion improvement in all treated dogs (n = 8). This cohort highlights resemblances between human and canine MIS. Further studies are required to confirm these findings and establish diagnostic criteria for CM and MIS associated with SM in dogs.</p>","PeriodicalId":23693,"journal":{"name":"Veterinary and comparative oncology","volume":" ","pages":"136-148"},"PeriodicalIF":2.1,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139513599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Comparison of the anticancer effects of various statins on canine oral melanoma cells.","authors":"Takuro Ishikawa, Nanami Irie, Jiro Tashiro, Tomohiro Osaki, Tomoko Warita, Katsuhiko Warita, Munekazu Naito","doi":"10.1111/vco.12946","DOIUrl":"10.1111/vco.12946","url":null,"abstract":"<p><p>Canine oral melanoma is a highly malignant cancer with a poor prognosis. Statins, commonly used drugs for treating dyslipidemia, exhibit pleiotropic anticancer effects and marked anti-proliferative effects against melanoma cells. The anticancer effects among statins vary; in human cancers, lipophilic statins have shown stronger anticancer effects compared with hydrophilic statins. However, data on the differences in the effects of various statins on canine cancer cells are lacking, hence the optimal statins for treating canine melanoma remain unknown. Therefore, this study aimed to clarify the most effective statin by comparing the anticancer effects of hydrophilic rosuvastatin and lipophilic atorvastatin, simvastatin, fluvastatin and pitavastatin on three canine oral melanoma cell lines. Time-dependent measurement of cell confluence showed that lipophilic statins had a stronger anti-proliferative effect on all cell lines than hydrophilic rosuvastatin. Quantification of lactate dehydrogenase release, an indicator of cytotoxicity, showed that lipophilic statins more effectively induced cell death than hydrophilic rosuvastatin. Lipophilic statins affected both inhibition of cell proliferation and induction of cell death. The anticancer effects of statins on canine oral melanoma cells differed in the following ascending order of IC<sub>50</sub> values: pitavastatin < fluvastatin = simvastatin < atorvastatin < rosuvastatin. The required concentration of pitavastatin was approximately 1/20th that of rosuvastatin. Among the statins used in this study, pitavastatin had the highest anticancer effect. Our results suggest lipophilic pitavastatin as the optimal statin for treating canine oral melanoma.</p>","PeriodicalId":23693,"journal":{"name":"Veterinary and comparative oncology","volume":" ","pages":"156-161"},"PeriodicalIF":2.1,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138478716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hiroshi Miyagi, Katy L Townsend, Alyssa Michael Ettinger, Duncan S Russell, James C Colee, Lauren Elizabeth Newsom
{"title":"Correlation between computed tomography and histological evaluation of nodal metastasis in dogs with mast cell tumours.","authors":"Hiroshi Miyagi, Katy L Townsend, Alyssa Michael Ettinger, Duncan S Russell, James C Colee, Lauren Elizabeth Newsom","doi":"10.1111/vco.12947","DOIUrl":"10.1111/vco.12947","url":null,"abstract":"<p><p>Early diagnosis of nodal metastasis has been shown to impact prognosis for dogs with mast cell tumours (MCT). The objective of this retrospective study was to determine the correlation between computed tomographic characteristics of lymph nodes and histologic nodal metastasis using the HN classification system, in dogs with cutaneous or subcutaneous MCT and regional lymph node(s) removal. Dogs that had removal of MCT and regional lymphadenectomy within 31 days of the initial staging computed tomography (CT) were enrolled. Subjective lymph node characteristics used included margination, loss of fat at hilus, shape of margin, perinodal fat pattern, increase in number of nodes, and pre- and post-contrast heterogeneity. Enhancement, heterogeneity, and short-long axis ratio were calculated. Seventy-one lymph nodes from 37 dogs were included. Generalised linear mixed model of assessment of lymph node was performed twice, with binary outcome [non-metastatic (HN0/1) versus metastatic (HN2/3)] and 4-point scales (HN0-HN3). After blind assessment of 7 characteristics described above, a final subjective interpretation of each lymph node as non-metastatic or metastatic was assigned. A significant correlation was found between final interpretation and prediction of metastasis. Higher HN classification was also significantly correlated with the increased number of nodes and pre- and post-contrast heterogeneity. No correlation was found in short-long axis ratio, calculated heterogeneity, or degree of enhancement. Sensitivity of CT was 35.7%, specificity was 96.6%, and accuracy was 60.5% for nodal metastasis. CT alone cannot be recommended for assessment of metastasis. The use of multiple computed tomographic characteristics may increase accuracy of nodal metastasis detection.</p>","PeriodicalId":23693,"journal":{"name":"Veterinary and comparative oncology","volume":" ","pages":"49-56"},"PeriodicalIF":2.1,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138478717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Petros Odatzoglou, Thomas Kearns, Charlie Pittaway, Jane M Dobson
{"title":"Impact of palliative-intent radiotherapy with or without chemotherapy on lameness in flat coat retrievers with localised periarticular histiocytic sarcoma - a retrospective cohort, single institution study.","authors":"Petros Odatzoglou, Thomas Kearns, Charlie Pittaway, Jane M Dobson","doi":"10.1111/vco.12942","DOIUrl":"10.1111/vco.12942","url":null,"abstract":"<p><p>Histiocytic sarcoma (HS) is a common tumour in flat coat retrievers (FCRs) often affecting periarticular tissues and joints. Palliative-intent radiotherapy, seeks to achieve local tumour control, pain relief and improve limb function. However, the effect of palliative-intent radiotherapy on analgesic levels of dogs with localised HS has not been studied. We hypothesised that palliative-intent radiotherapy could improve lameness in dogs affected by localised HS. This study aimed to assess the impact of palliative-intent radiotherapy on lameness of FCRs with localised HS. A retrospective cohort single institution study was performed. Medical records of FCR dogs with HS that received external beam radiotherapy between 2003 and 2022 were reviewed and included demographic, staging, severity of baseline lameness, therapeutic management and outcome data. Descriptive statistics, McNemar's chi-squared test, Fisher's exact test and Kaplan-Meier analysis were used for statistical analysis. Thirty-nine dogs were included with a median age of 7.2 years, 25 were male and 14 were female. HS was most commonly located in the forelimb (29 dogs, 74.3%), affecting the shoulder joint (19 dogs, 48.7%). Staging was performed in all 39 dogs with 22 (56.4%) dogs having localised HS, six (15.3%) dogs had localised HS with node metastasis and 11 (28.2%) dogs had localised HS with systemic metastasis. All dogs received palliative-intent hypo-fractionated radiation therapy, 32 (82%) dogs showed improvement in lameness. In conclusion, palliative intent radiation treatment has an analgesic effect reducing lameness or clinical signs associated with affected tumour-bearing joints.</p>","PeriodicalId":23693,"journal":{"name":"Veterinary and comparative oncology","volume":" ","pages":"22-29"},"PeriodicalIF":2.1,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71486651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Evaluation of the health-related quality of life in dogs following intracranial meningioma resection using a specifically developed questionnaire.","authors":"Chiara Köcher, Alexander Tichy, Gabriele Gradner","doi":"10.1111/vco.12956","DOIUrl":"10.1111/vco.12956","url":null,"abstract":"<p><p>As advanced treatments are becoming increasingly feasible in veterinary medicine, the evaluation of the health-related quality of life (HRQOL) of treated animals is becoming more relevant. We evaluated owner-perceived HRQOL of 10 dogs that underwent craniotomy for meningioma resection between 2002 and 2022 at our institution through telephone interview. For this purpose, we developed a disease-specific questionnaire containing 52 items (mostly of scoring nature) patterned after previously validated instruments and organised into eight domains. Approval by the Human Ethical Committee and respondents' consent were obtained. We analysed the scores for all domains and dogs. The effect of different variables on the HRQOL score was determined via log-rank test and Pearson correlation. Scores for all included dogs (range, 0-235 points) were totaled, with a higher number of points indicating a better HRQOL. The dogs included in this study yielded a mean score of 200.6 points (range, 176-227 points), implying a good overall quality of life. There were no significant associations between individual parameters and outcomes. Our questionnaire represents a structured tool for the specific evaluation of postoperative HRQOL in dogs with meningioma, placing a minimal burden on respondents. Few instruments have been developed to assess animal welfare in a disease-specific context. Implementing these tools, however, is essential to accurately evaluate not only the impact of treatments on biologic parameters, but also their implications on patient welfare. Thus, treatment plans may consider HRQOL for a more comprehensive clinical decision-making process.</p>","PeriodicalId":23693,"journal":{"name":"Veterinary and comparative oncology","volume":" ","pages":"89-95"},"PeriodicalIF":2.1,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139049392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nicholas E Prevedel, Miles W Mee, Geoffrey A Wood, Brenda L Coomber
{"title":"Effect of proteasome inhibitors on canine lymphoma cell response to CHOP chemotherapy in vitro.","authors":"Nicholas E Prevedel, Miles W Mee, Geoffrey A Wood, Brenda L Coomber","doi":"10.1111/vco.12957","DOIUrl":"10.1111/vco.12957","url":null,"abstract":"<p><p>The standard treatment for canine lymphoma is the CHOP chemotherapy regimen. Proteasome inhibitors have been employed with CHOP for the treatment of human haematological malignancies but remain to be fully explored in canine lymphoma. We identified an association between poor response to CHOP chemotherapy and high mRNA expression levels of proteasomal subunits in a cohort of 15 canine lymphoma patients, and sought to determine the effect of proteasome inhibitors on the viability of a canine B-cell lymphoma cell line (CLBL-1). The aim of this study was to investigate whether proteasome inhibitors sensitize these cells to the CHOP agents doxorubicin, vincristine and cyclophosphamide (as 4-hydroxycyclophosphamide/4-HC). CLBL-1 cells were sensitive to proteasome inhibition by bortezomib and ixazomib. The IC<sub>50</sub> of bortezomib was 15.1 nM and of ixazomib was 59.14 nM. Proteasome inhibitors plus doxorubicin had a synergistic effect on CLBL-1 viability; proteosome inhibitors plus vincristine showed different effects depending on the combination ratio, and there was an antagonistic effect with 4-HC. These results may have clinical utility, as proteasome inhibition could potentially be used with a synergizing CHOP compound to improve responsiveness to chemotherapy for canine lymphoma patients.</p>","PeriodicalId":23693,"journal":{"name":"Veterinary and comparative oncology","volume":" ","pages":"96-105"},"PeriodicalIF":2.1,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139492193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}