Pub Date : 2024-03-01Epub Date: 2023-11-29DOI: 10.1111/vco.12943
Gennaro Altamura, Manuela Martano, Anna Matrone, Annunziata Corteggio, Giuseppe Borzacchiello
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.
{"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":null,"pages":null},"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}
Pub Date : 2024-03-01Epub Date: 2023-12-01DOI: 10.1111/vco.12945
Chiara Agnoli, Sofia Rimondi, Giulia Ghisoni, Dina Guerra, Michele Tumbarello, Simone Perfetti, Alessandro Tirolo, Laura Marconato
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/m2 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.
卡培他滨是5-氟尿嘧啶的口服前药,用于治疗各种恶性上皮癌。在狗身上,卡培他滨尚未被广泛评估。本回顾性研究的目的是探讨单药卡培他滨对任何部位的晚期恶性上皮癌犬的毒性和初步疗效,这些犬没有有效的治疗方法,常规治疗失败或拒绝。卡培他滨从第1天到第14天口服750 mg/m2,然后休息1周,以3周为一个周期。2个周期后进行安全性评价,此后每2-3个周期进行一次安全性评价。每2-3个周期检测肿瘤反应。25只患有肝细胞癌(n = 6)、肺乳头状癌(n = 4)、肛管腺癌(n = 3)、结肠腺癌(n = 2)和其他单独代表的上皮癌(n = 10)的狗被纳入研究。狗接受了中位数为4个周期(范围2-43),中位数为84天(范围42-913)。17只(68.0%)犬中毒;最常见的不良事件是胃肠道,大多数是自行解决和轻度。22只肉眼病变犬中,部分缓解3只(13.6%),病情稳定16只(72.7%),病情进展3只(13.6%);临床总有效率为86.4%。中位无进展间隔为93天(95% CI 42-154;范围,1-521),中位肿瘤特异性生存期为273天(95% CI 116-482;45 - 913)范围。这些发现表明,卡培他滨是一种有吸引力的选择,用于治疗几种类型的狗癌。有必要进行前瞻性研究以优化卡培他滨的用药计划并确认其疗效。
{"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":null,"pages":null},"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}
Pub Date : 2024-03-01Epub Date: 2023-12-28DOI: 10.1111/vco.12958
Antony Stewart Moore, Angela Erica Frimberger
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).
{"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":null,"pages":null},"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}
Pub Date : 2024-03-01Epub Date: 2024-01-20DOI: 10.1111/vco.12962
Eleanor K Wyatt, Verena Affolter, Stefano Borio, Alexandra Guillen, Sara Verganti, Sue Murphy, Damiano Ballarini, Frane Banovic, Vanessa Schmidt, Jean-Benoit Tanis
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.
犬皮肤肥大细胞增多症(CM)与犬肥大细胞瘤相比非常罕见。犬皮肤肥大细胞增多症(CM)与犬肥大细胞瘤相比较为罕见。在人类中,犬皮肤肥大细胞增多症常见于儿童,通常症状不明显,可自行缓解。骨髓受累的全身性肥大细胞增生症(SM)通常会影响成年人,预后较差,而且通常会出现皮肤病变。皮肤肥大细胞增多症"(Mastocytosis in the skin,MIS)是皮肤病变的首选术语,如果无法进行骨髓评估的话,狗的情况往往如此。在人类 SM 和 CM 中,通常会检测到 KIT 突变。兽医文献表明,人类和犬类 MIS 的临床表现相似,但数据有限,而且很少对 KIT 基因突变进行评估。这项回顾性研究描述了 11 只疑似肥大细胞瘤犬的临床病理结果、治疗和预后。排除了患有多发性肥大细胞瘤的犬只。对组织病理学报告(5 例)或切片(6 例)进行了审查。对 8 只狗进行了 KIT 突变分析,包括第 8、9、11、14 和 17 号外显子。确诊时的中位年龄为 4 岁(1-12 岁)。典型的临床症状包括多灶性至全身性结节和丘疹。组织学上,皮肤病变的特征是真皮浸润分化良好的肥大细胞。3/8只狗检测到KIT突变(外显子9:n = 2;外显子11:n = 1)。一只狗患有肥大细胞血症,提示可能患有 SM。糖皮质激素在所有接受治疗的狗(n = 8)中都取得了成功,病变得到了改善。该队列突出了人类和犬类 MIS 之间的相似性。需要进一步的研究来证实这些发现,并建立与犬 SM 相关的 CM 和 MIS 的诊断标准。
{"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":null,"pages":null},"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}
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 IC50 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.
{"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":null,"pages":null},"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}
Pub Date : 2024-03-01Epub Date: 2023-12-03DOI: 10.1111/vco.12947
Hiroshi Miyagi, Katy L Townsend, Alyssa Michael Ettinger, Duncan S Russell, James C Colee, Lauren Elizabeth Newsom
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.
{"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":null,"pages":null},"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}
Pub Date : 2024-03-01Epub Date: 2023-11-07DOI: 10.1111/vco.12942
Petros Odatzoglou, Thomas Kearns, Charlie Pittaway, Jane M Dobson
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.
{"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":null,"pages":null},"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}
Pub Date : 2024-03-01Epub Date: 2023-12-27DOI: 10.1111/vco.12956
Chiara Köcher, Alexander Tichy, Gabriele Gradner
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.
{"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":null,"pages":null},"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}
Pub Date : 2024-03-01Epub Date: 2024-01-18DOI: 10.1111/vco.12957
Nicholas E Prevedel, Miles W Mee, Geoffrey A Wood, Brenda L Coomber
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 IC50 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.
犬淋巴瘤的标准治疗方法是 CHOP 化疗方案。蛋白酶体抑制剂已与 CHOP 一起用于人类血液恶性肿瘤的治疗,但在犬淋巴瘤的治疗中仍有待充分探索。我们在一组 15 名犬淋巴瘤患者中发现了对 CHOP 化疗反应差与蛋白酶体亚基 mRNA 表达水平高之间的关联,并试图确定蛋白酶体抑制剂对犬 B 细胞淋巴瘤细胞系(CLBL-1)活力的影响。这项研究的目的是调查蛋白酶体抑制剂是否会使这些细胞对CHOP药物多柔比星、长春新碱和环磷酰胺(4-羟基环磷酰胺/4-HC)敏感。CLBL-1 细胞对硼替佐米和伊沙佐米的蛋白酶体抑制作用敏感。硼替佐米的 IC50 为 15.1 nM,ixazomib 为 59.14 nM。蛋白酶体抑制剂加多柔比星对CLBL-1的存活率有协同作用;蛋白酶体抑制剂加长春新碱的作用因组合比例的不同而不同,加4-HC则有拮抗作用。这些结果可能具有临床实用性,因为蛋白酶体抑制剂有可能与增效的CHOP化合物一起使用,以提高犬淋巴瘤患者对化疗的反应性。
{"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":null,"pages":null},"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}
Pub Date : 2024-03-01Epub Date: 2023-11-07DOI: 10.1111/vco.12940
Cailin R Heinze, Kristine E Burgess, Lisa G Barber, Kenneth M Rassnick, Gerald S Post, Richard Segaloff, Julie Bayle
Quality of life (QOL) in dogs with cancer is a key consideration in the assessment of cancer treatment options. Despite interest in dietary strategies to improve management of oncology patients, there have been very few clinical studies showing the impact of diet on adverse effects of chemotherapy in dogs. This study was a randomised, controlled, double-blinded, multicenter clinical trial to investigate a high-protein, increased-fibre diet supplemented with omega-3 fatty acids, for dogs with cancer undergoing standard-of-care chemotherapy. Client-owned dogs with newly diagnosed grade 2 or higher mast cell tumours (or non-resectable/incompletely resected tumours) or multicentric lymphoma were randomised to receive the test diet (n = 24) or control diet (n = 21) for 8 weeks. Primary outcomes were QOL assessments, faecal scores, and blood concentrations of C-reactive protein and monocyte chemoattractant protein-1. Of 12 QOL parameters, 10 significantly improved from baseline to Week 8 in the test group compared with one in the control group. However, differences between the two groups were only statistically significant for 'frequency of signs of illness' (P = .009). There were no significant differences in the incidence of any adverse events, including gastrointestinal adverse events or clinically significant differences in laboratory parameters or faecal scores between the two groups. The absence of an observed negative impact of the test diet, combined with the magnitude of QOL improvements associated with the diet, suggest that a larger trial is warranted.
{"title":"Effects of a high-protein, increased-fibre, dry diet supplemented with omega-3 fatty acids on quality of life in dogs undergoing chemotherapy.","authors":"Cailin R Heinze, Kristine E Burgess, Lisa G Barber, Kenneth M Rassnick, Gerald S Post, Richard Segaloff, Julie Bayle","doi":"10.1111/vco.12940","DOIUrl":"10.1111/vco.12940","url":null,"abstract":"<p><p>Quality of life (QOL) in dogs with cancer is a key consideration in the assessment of cancer treatment options. Despite interest in dietary strategies to improve management of oncology patients, there have been very few clinical studies showing the impact of diet on adverse effects of chemotherapy in dogs. This study was a randomised, controlled, double-blinded, multicenter clinical trial to investigate a high-protein, increased-fibre diet supplemented with omega-3 fatty acids, for dogs with cancer undergoing standard-of-care chemotherapy. Client-owned dogs with newly diagnosed grade 2 or higher mast cell tumours (or non-resectable/incompletely resected tumours) or multicentric lymphoma were randomised to receive the test diet (n = 24) or control diet (n = 21) for 8 weeks. Primary outcomes were QOL assessments, faecal scores, and blood concentrations of C-reactive protein and monocyte chemoattractant protein-1. Of 12 QOL parameters, 10 significantly improved from baseline to Week 8 in the test group compared with one in the control group. However, differences between the two groups were only statistically significant for 'frequency of signs of illness' (P = .009). There were no significant differences in the incidence of any adverse events, including gastrointestinal adverse events or clinically significant differences in laboratory parameters or faecal scores between the two groups. The absence of an observed negative impact of the test diet, combined with the magnitude of QOL improvements associated with the diet, suggest that a larger trial is warranted.</p>","PeriodicalId":23693,"journal":{"name":"Veterinary and comparative oncology","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11115191/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71486650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}