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Monoclonal antibody cetuximab impairs matrix metalloproteinases 2 and 9, epithelial-mesenchymal transition and cell migration in feline oral squamous cell carcinoma in vitro. 单克隆抗体西妥昔单抗对猫口腔鳞状细胞癌基质金属蛋白酶2和9、上皮-间质转化和细胞迁移的影响
IF 2.1 2区 农林科学 Q1 Veterinary Pub Date : 2024-03-01 Epub Date: 2023-11-29 DOI: 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.

猫口腔鳞状细胞癌(FOSCC)的特点是侵袭性和转移性行为,对目前的治疗反应较差,因此需要新的治疗策略。FOSCC与人头颈部鳞状细胞癌(HNSCC)有共同的分子靶点,其中包括表皮生长因子受体。西妥昔单抗是一种用于治疗HNSCC的抗表皮生长因子受体单克隆抗体,有趣的是,之前的体外研究表明,西妥昔单抗也具有抗FOSCC的细胞抑制和细胞毒性。在本研究中,我们旨在进一步研究西妥昔单抗对已证实与人类患者相关的侵袭和转移途径的影响。为此,用西妥昔单抗处理FOSCC细胞系SCCF1、SCCF2和SCCF3 48/72 h,并进行基质金属蛋白酶-2/9 (MMP-2/9)和上皮-间质转化标记物vimentin、E-、P-和n -钙粘蛋白的Western blot检测。西妥昔单抗治疗导致所有三种细胞系中MMP-2/-9呈剂量依赖性下调。此外,西妥昔单抗下调SCCF1中的vimentin和P-cadherin,上调SCCF2中的E-cadherin,下调SCCF2中的P-/N-cadherins,损害SCCF3中的P-/N-cadherins。体外划痕试验也表明西妥昔单抗延迟SCCF3的细胞迁移。这些数据表明,西妥昔单抗通过损害FOSCC的MMPs和上皮-间质转化途径来减轻侵袭和转移过程,表明这种单克隆抗体可能有助于抑制恶性进展并改善局部侵袭性疾病的管理。
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引用次数: 0
Spotlight on capecitabine for the treatment of unresectable or metastatic carcinoma of various origin: A retrospective study of 25 dogs. 聚焦卡培他滨治疗各种来源的不可切除或转移性癌:25只狗的回顾性研究。
IF 2.1 2区 农林科学 Q1 Veterinary Pub Date : 2024-03-01 Epub Date: 2023-12-01 DOI: 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。
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引用次数: 0
Treatment of feline intermediate to high-grade alimentary lymphoma: A retrospective evaluation of 55 cats treated with the VAPC combination chemotherapy protocol (2017-2021). 猫中高级消化道淋巴瘤的治疗:采用VAPC联合化疗方案治疗55只猫的回顾性评估(2017-2021年)。
IF 2.1 2区 农林科学 Q1 Veterinary Pub Date : 2024-03-01 Epub Date: 2023-12-28 DOI: 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).

治疗猫淋巴瘤最常用的方案是使用长春新碱、环磷酰胺和泼尼松,有时还会使用 L-天冬酰胺酶和多柔比星等其他药物。我们对 55 只患有消化道淋巴瘤的猫的病历进行了审查,这些猫接受了一种新型多药方案(VAPC 方案)的治疗,该方案使用了泼尼松龙、L-天冬酰胺酶、多柔比星、长春新碱而不是长春新碱、较高剂量的环磷酰胺和口服丙卡巴嗪。评估结果包括治疗反应、毒性和无进展生存期(PFS)。3级或4级中性粒细胞减少症是化疗剂量调整最常见的治疗相关原因,52只接受长春新碱化疗的猫中有8只出现了这种情况,55只接受环磷酰胺化疗的猫中有7只出现了这种情况,40只接受多柔比星化疗的猫中有1只出现了这种情况,但只有2只猫出现了发热性中性粒细胞减少症。在因可测量疾病而接受化疗的 38 只猫中,有 26 只(68.4%)获得了完全应答 (CR)。3只猫获得了部分应答,9只猫未能获得缓解。没有发现影响猫咪是否可能获得 CR 的因素。在所有 55 只猫(包括接受化疗和手术的猫)中,中位生存期为 184 天,1 年、2 年和 3 年生存率分别为 35.4%、26.5% 和 26.5%。经多变量分析,40 只达到 CR 的猫的中位生存时间为 341 天(PR 为 78 天,NR 为 45 天);淋巴细胞与单核细胞的 L:M 比率(>3.4 = 700 天 vs. ≤3.4 = 126 天)和 B 细胞与 T 细胞表型(分别为 220 天 vs. 42 天)也会显著影响 PFS 时间。
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引用次数: 0
Mastocytosis in the skin in dogs: A multicentric case series. 狗皮肤上的肥大细胞增多症:多中心病例系列。
IF 2.1 2区 农林科学 Q1 Veterinary Pub Date : 2024-03-01 Epub Date: 2024-01-20 DOI: 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。
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引用次数: 0
Comparison of the anticancer effects of various statins on canine oral melanoma cells. 不同他汀类药物对犬口腔黑色素瘤细胞抗癌作用的比较。
IF 2.1 2区 农林科学 Q1 Veterinary Pub Date : 2024-03-01 Epub Date: 2023-12-03 DOI: 10.1111/vco.12946
Takuro Ishikawa, Nanami Irie, Jiro Tashiro, Tomohiro Osaki, Tomoko Warita, Katsuhiko Warita, Munekazu Naito

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.

犬口腔黑色素瘤是一种预后不良的高度恶性肿瘤。他汀类药物是治疗血脂异常的常用药物,具有多效抗癌作用,对黑色素瘤细胞具有显著的抗增殖作用。他汀类药物的抗癌作用各不相同;在人类癌症中,亲脂他汀类药物比亲水他汀类药物显示出更强的抗癌作用。然而,关于各种他汀类药物对犬癌细胞的影响差异的数据缺乏,因此治疗犬黑色素瘤的最佳他汀类药物仍然未知。因此,本研究旨在通过比较亲水性瑞舒伐他汀与亲脂性阿托伐他汀、辛伐他汀、氟伐他汀和匹伐他汀对三种犬口腔黑色素瘤细胞系的抗癌作用,阐明最有效的他汀类药物。细胞融合的时间依赖性测量显示,亲脂性他汀类药物对所有细胞系的抗增殖作用都强于亲水性瑞舒伐他汀。乳酸脱氢酶释放(细胞毒性指标)的定量显示,亲脂性他汀类药物比亲水性瑞舒伐他汀更有效地诱导细胞死亡。亲脂性他汀类药物对细胞增殖的抑制和细胞死亡的诱导均有影响。他汀类药物对犬口腔黑色素瘤细胞的抗癌作用,其IC50值从高到低依次为:匹伐他汀
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引用次数: 0
Correlation between computed tomography and histological evaluation of nodal metastasis in dogs with mast cell tumours. 肥大细胞瘤犬淋巴结转移的计算机断层扫描与组织学评价的相关性。
IF 2.1 2区 农林科学 Q1 Veterinary Pub Date : 2024-03-01 Epub Date: 2023-12-03 DOI: 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.

淋巴结转移的早期诊断已被证明会影响肥大细胞瘤(MCT)犬的预后。本回顾性研究的目的是利用HN分类系统,在皮肤或皮下MCT和区域淋巴结切除的狗中,确定淋巴结的计算机断层特征与组织学淋巴结转移之间的相关性。在初始阶段计算机断层扫描(CT)后31天内进行MCT切除和局部淋巴结切除术的狗被纳入研究。主观淋巴结特征包括边缘、门部脂肪减少、边缘形状、结周脂肪分布、淋巴结数量增加、对比前后异质性。计算增强、异质性和长短轴比。包括37只狗的71个淋巴结。采用广义线性混合模型进行两次淋巴结评估,二元结果[非转移性(HN0/1) vs转移性(HN2/3)]和4点量表(HN0-HN3)。在对上述7个特征进行盲评估后,对每个淋巴结的最终主观解释为非转移性或转移性。在最终解释和转移预测之间发现了显著的相关性。较高的HN分级也与淋巴结数量增加以及对比前后异质性显著相关。在长短轴比、计算异质性或增强程度方面均未发现相关性。CT对淋巴结转移的敏感性为35.7%,特异性为96.6%,准确性为60.5%。CT不能单独用于评估转移。使用多重计算机断层特征可以提高淋巴结转移检测的准确性。
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引用次数: 0
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. 姑息性放疗加或不加化疗对局部关节周围组织细胞肉瘤扁平毛寻回犬跛行的影响——一项回顾性队列、单一机构研究。
IF 2.1 2区 农林科学 Q1 Veterinary Pub Date : 2024-03-01 Epub Date: 2023-11-07 DOI: 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.

组织细胞肉瘤(HS)是扁平毛寻回犬(FCRs)中常见的肿瘤,通常影响关节周围组织和关节。意向性姑息性放射治疗,旨在实现局部肿瘤控制、疼痛缓解和改善肢体功能。然而,姑息性放疗对局部HS犬镇痛水平的影响尚未得到研究。我们假设,姑息性放疗可以改善局部HS影响的狗的跛行。本研究旨在评估姑息性放疗对伴有局部HS的FCRs跛行的影响。进行了一项回顾性队列单机构研究。回顾了2003年至2022年间接受外束放射治疗的患有HS的FCR犬的医疗记录,包括人口统计学、分期、基线跛行的严重程度、治疗管理和结果数据。统计分析采用描述性统计学、McNemar卡方检验、Fisher精确检验和Kaplan-Meier分析。39只狗被纳入研究,中位年龄为7.2岁 男25例,女14例。HS最常见于前肢(29只,74.3%),影响肩关节(19只,48.7%)。对所有39只狗进行了分期,其中22只(56.4%)狗患有局部HS,6只(15.3%)狗患有伴有淋巴结转移的局部HS,11只(28.2%)狗患有伴有全身转移的局部性HS。所有狗都接受了姑息性低分级放射治疗,32只(82%)狗的跛行情况有所改善。总之,姑息性放射治疗具有镇痛作用,可以减少跛足或与受影响的肿瘤关节相关的临床症状。
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引用次数: 0
Evaluation of the health-related quality of life in dogs following intracranial meningioma resection using a specifically developed questionnaire. 使用专门编制的调查问卷,评估颅内脑膜瘤切除术后狗的健康相关生活质量。
IF 2.1 2区 农林科学 Q1 Veterinary Pub Date : 2024-03-01 Epub Date: 2023-12-27 DOI: 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.

随着先进疗法在兽医领域的应用越来越广泛,对接受治疗的动物的健康相关生活质量(HRQOL)进行评估也变得越来越重要。我们通过电话访问的方式,对本机构在 2002 年至 2022 年期间接受开颅脑膜瘤切除术的 10 只犬进行了主人感知的 HRQOL 评估。为此,我们开发了一份针对特定疾病的调查问卷,其中包含 52 个项目(大部分为评分性质),这些项目均以以前的有效工具为蓝本,并分为 8 个领域。我们已获得人类伦理委员会的批准和受访者的同意。我们分析了所有领域和狗的得分。不同变量对 HRQOL 分数的影响通过对数秩检验和皮尔逊相关性来确定。我们对所有纳入研究的犬只进行了总分(范围为 0-235 分),分数越高,表示 HRQOL 越好。本研究中的狗狗平均得分为 200.6 分(范围为 176-227 分),这意味着狗狗的整体生活质量较高。单个参数与结果之间没有明显关联。我们的调查问卷是一种结构化工具,可用于具体评估脑膜瘤患犬的术后生活质量,对受访者造成的负担极小。针对特定疾病的动物福利评估工具还很少。然而,要准确评估治疗对生物参数的影响以及对患者福利的影响,就必须使用这些工具。因此,治疗计划可以考虑 HRQOL,以实现更全面的临床决策过程。
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引用次数: 0
Effect of proteasome inhibitors on canine lymphoma cell response to CHOP chemotherapy in vitro. 蛋白酶体抑制剂对犬淋巴瘤细胞对体外 CHOP 化疗反应的影响。
IF 2.1 2区 农林科学 Q1 Veterinary Pub Date : 2024-03-01 Epub Date: 2024-01-18 DOI: 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。
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引用次数: 0
Effects of a high-protein, increased-fibre, dry diet supplemented with omega-3 fatty acids on quality of life in dogs undergoing chemotherapy. 高蛋白、增加纤维、补充ω-3脂肪酸的干燥饮食对接受化疗的狗的生活质量的影响。
IF 2.1 2区 农林科学 Q1 Veterinary Pub Date : 2024-03-01 Epub Date: 2023-11-07 DOI: 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.

癌症狗的生活质量(QOL)是评估癌症治疗方案的关键考虑因素。尽管人们对改善肿瘤患者管理的饮食策略感兴趣,但很少有临床研究表明饮食对狗化疗不良反应的影响。这项研究是一项随机、对照、双盲、多中心临床试验,旨在为接受标准护理化疗的癌症狗研究补充ω-3脂肪酸的高蛋白、高纤维饮食。患有新诊断的2级或更高级别肥大细胞肿瘤(或不可切除/不完全切除的肿瘤)或多中心淋巴瘤的客户饲养的狗被随机分配接受试验饮食(n = 24)或对照饮食(n = 21)用于8 周。主要结果是生活质量评估、粪便评分以及血液中C反应蛋白和单核细胞趋化蛋白-1的浓度。在12个生活质量参数中,与对照组的1个相比,试验组的10个从基线到第8周显著改善。然而,两组之间的差异仅在“疾病迹象的频率”方面具有统计学意义(P = .009)。两组之间任何不良事件(包括胃肠道不良事件)的发生率均无显著差异,实验室参数或粪便评分也无临床显著差异。没有观察到试验饮食的负面影响,再加上与饮食相关的生活质量改善幅度,表明有必要进行更大规模的试验。
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Veterinary and comparative oncology
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