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Identification of a novel ephemerovirus in a water buffalo (Bubalus bubalis [Linnaeus, 1758]). 在一头水牛(Bubalus bubalis [Linnaeus, 1758])身上鉴定出一种新型附病毒。
IF 1.1 4区 农林科学 Q3 VETERINARY SCIENCES Pub Date : 2024-11-15 Epub Date: 2024-10-08 DOI: 10.1292/jvms.24-0295
Sakiho Imai, Mai Kishimoto, Masayuki Horie

Ephemeroviruses, belonging to the genus Ephemerovirus within the family Rhabdoviridae of the Mononegavirales, are non-segmented, negative-strand RNA viruses that infect artiodactyls and blood-sucking arthropods. Although recent advances in sequencing technology have facilitated the identification of novel ephemeroviruses, thereby expanding our understanding of this viral genus, their diversity remains elusive, as evidenced by phylogenetic gaps between currently known ephemeroviruses. In this study, we analyzed publicly available RNA-seq data and identified a novel ephemerovirus, tentatively named Punjab virus (PBV), in a water buffalo (Bubalus bubalis [Linnaeus, 1758]). We obtained two separate PBV contigs from the RNA-seq data; the first contig covers the N, P, and M genes, while the second contig covers the G, α, β, γ, and L genes. Together, these PBV contigs represent 99% of the estimated complete viral genome. Mapping analysis revealed a typical transcriptional gradient pattern commonly observed in mononegaviruses, suggesting that the water buffalo is the authentic host for PBV. Sequence comparisons with its closest relatives indicate that the newly identified virus meets the ICTV species demarcation criteria for sequence divergence. Thus, this study contributes to a deeper understanding of the diversity of ephemeroviruses.

蜉蝣病毒属于单核病毒科蜉蝣病毒属,是一种非片段、负链 RNA 病毒,可感染节肢动物和吸血节肢动物。尽管最近测序技术的进步促进了新型短暂病毒的鉴定,从而扩大了我们对这一病毒属的了解,但它们的多样性仍然难以捉摸,目前已知短暂病毒之间的系统发育差距就证明了这一点。在本研究中,我们分析了公开的 RNA-seq 数据,在一头水牛(Bubalus bubalis [Linnaeus, 1758])体内发现了一种新型短暂病毒,暂命名为旁遮普病毒(PBV)。我们从 RNA-seq 数据中获得了两个独立的 PBV 等位基因;第一个等位基因涵盖 N、P 和 M 基因,第二个等位基因涵盖 G、α、β、γ 和 L 基因。这些 PBV 等位基因加在一起占估计完整病毒基因组的 99%。图谱分析显示了单核病毒中常见的典型转录梯度模式,表明水牛是 PBV 的真正宿主。与近亲的序列比较表明,新发现的病毒符合 ICTV 序列分歧的物种划分标准。因此,这项研究有助于加深对短暂病毒多样性的理解。
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引用次数: 0
Genetic investigation of glycosylphosphatidylinositol (GPI) anchored Bd37 orthologs in Babesia divergens group and potential use of recombinant protein for ecological survey in deer. 糖基磷脂酰肌醇(GPI)锚定 Bd37 同源物的遗传学调查和重组蛋白在鹿生态调查中的潜在用途。
IF 1.1 4区 农林科学 Q3 VETERINARY SCIENCES Pub Date : 2024-11-15 Epub Date: 2024-10-07 DOI: 10.1292/jvms.24-0116
Aya Zamoto-Niikura, Katsuro Hagiwara, Koichi Imaoka, Shigeru Morikawa, Ken-Ichi Hanaki

The Babesia divergens/B. capreoli group includes parasites with confirmed or possible zoonotic potential to cause human babesiosis. Currently, diagnostic antigen of the group has not been established. In this study, we investigated the ortholog of Bd37, a glycosylphosphatidylinositol (GPI)-anchored major merozoite surface protein of B. divergens sensu stricto, in the Asia lineage of the group. From two genomic isolates from sporozoite/sporoblast stages, three Bd37 gene variants, namely Bd37 JP-A, JP-B, and JP-C, were isolated with 62.3-64.1% amino acid sequence identity. Discriminative blood direct PCR revealed that Bd37 JP-A was encoded in all parasites infecting wild sika deer examined (n=22). While Bd37 JP-B and JP-C genes were randomly detected in 12 and 11 specimens, respectively. Sequencing of all JP-A variants revealed that the gene was polymorphic, with a low ratio of non-synonymous to synonymous substitutions (dN/dS) and that a highly polymorphic region was not related to predicted B-cell epitopes. A recombinant JP-A-based ELISA showed an overall positive rate of 13.9% in sika deer in Japan from north (Hokkaido) to south (Kyushu island) across 24 prefectures (n=360). This positive rate was twice as high as that examined by 18S rRNA-based PCR (6.6%). The geographical trends in infection rates were consistent. This study demonstrated that direct examination was informative for revealing genetic background and selecting antigen candidates. Bd37 orthologs may serve diagnostic purposes in combination with indirect fluorescence assay, which requires biological isolates.

卡普里奥利巴贝西亚原虫(Babesia divergens/B.capreoli)群包括经证实或可能具有人畜共患病潜能的寄生虫,可引起人类巴贝西亚原虫病。目前,该群体的诊断抗原尚未确定。在这项研究中,我们调查了该群体亚洲系中 Bd37 的直向同源物,Bd37 是严格意义上的分歧杆菌(B. divergens sensu stricto)的一种(GPI)锚定的主要分生孢子表面蛋白。从孢子虫/孢子母细胞阶段的两个基因组分离物中,分离出三个 Bd37 基因变体,即 Bd37 JP-A、JP-B 和 JP-C,其氨基酸序列的一致性为 62.3%-64.1%。血液直接聚合酶链式反应(PCR)的判别结果表明,所有感染野生梅花鹿的寄生虫(n=22)都编码 Bd37 JP-A。Bd37 JP-B和JP-C基因分别在12个和11个标本中随机检测到。对所有JP-A变体进行测序后发现,该基因具有多态性,非同义替换与同义替换的比率(dN/dS)较低,而且一个高度多态的区域与预测的B细胞表位无关。基于重组JP-A的酶联免疫吸附试验显示,在日本从北部(北海道)到南部(九州岛)的24个都道府县(n=360)的梅花鹿中,总体阳性率为13.9%。这一阳性率是基于 18S rRNA 的 PCR 检测结果(6.8%)的两倍。感染率的地域趋势是一致的。这项研究表明,直接检测对揭示遗传背景和选择候选抗原具有参考价值。Bd37 直向同源物与间接荧光检测相结合可达到诊断目的,但间接荧光检测需要生物分离物。
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引用次数: 0
The composition of early lactation milk in recipient dairy cows determines success in bovine embryo transfer. 受体奶牛的早期泌乳乳汁成分决定了牛胚胎移植的成功与否。
IF 1.1 4区 农林科学 Q3 VETERINARY SCIENCES Pub Date : 2024-11-15 Epub Date: 2024-09-27 DOI: 10.1292/jvms.24-0292
Toshihiro Takano, Akira Goto, Toshihisa Sugino

To identify new criteria for selecting recipient dairy cows for embryo transfer (ET), we retrospectively examined the effects of the composition of early lactation milk on fertility risk in ET. This study investigated the association between milk fat (FAT), milk protein (PRO), and milk urea nitrogen (MUN) levels during early lactation, based on production records, and subsequent fertility risk in ET using contingency table analysis and multivariable logistic regression analysis, which included five confounding variables. The results showed that MUN levels during early lactation were negatively associated with fertility risk in ET, while FAT and PRO levels showed no clear association. A reduction in MUN levels during the peak lactation period suggests a deficiency in dry matter intake, an inadequate protein supply, and an imbalance in the ratio of proteins to fermentable carbohydrates in the rumen, which may have adversely impacted fertility risk in ET. Monitoring MUN levels is crucial for maintaining a proper protein balance. The results obtained in this study suggest that MUN levels in the early lactation phase obtained from production records can be used as a predictor of fertility in recipients to improve the fertility risk in ET. No special techniques or costs are required for using production records, making them easy to use in clinical practice. Our findings provide valuable insights for optimizing cost-effectiveness and fertility risk in ET and their clinical applications.

为了确定选择受体奶牛进行胚胎移植(ET)的新标准,我们回顾性地研究了泌乳早期牛奶成分对ET生育风险的影响。本研究根据生产记录,采用或然率表分析和多变量逻辑回归分析(包括五个混杂变量),研究了泌乳早期乳脂(FAT)、乳蛋白(PRO)和乳尿素氮(MUN)水平与随后的ET生育风险之间的关系。结果表明,泌乳早期的MUN水平与ET的生育风险呈负相关,而FAT和PRO水平则无明显关联。泌乳高峰期MUN水平的降低表明干物质摄入不足、蛋白质供应不足以及瘤胃中蛋白质与可发酵碳水化合物的比例失调,这可能会对ET的生育风险产生不利影响。监测 MUN 水平对维持适当的蛋白质平衡至关重要。本研究的结果表明,从生产记录中获得的泌乳早期的 MUN 水平可用作受体繁殖力的预测指标,以改善 ET 的繁殖风险。使用生产记录不需要特殊的技术或成本,因此在临床实践中很容易使用。我们的研究结果为优化 ET 的成本效益和生育风险及其临床应用提供了宝贵的见解。
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引用次数: 0
Usefulness of noninvasive blood pressure measurement in captive Red Panda (Ailurus fulgens). 圈养小熊猫(Ailurus fulgens)无创血压测量的实用性。
IF 1.1 4区 农林科学 Q3 VETERINARY SCIENCES Pub Date : 2024-11-15 Epub Date: 2024-10-11 DOI: 10.1292/jvms.24-0060
Ran Kimura, Masafumi Kawano, Hiroki Matsutani, Momoe Suehiro, Keisuke Kawase, Shun-Ichi Shiihara, Rie Kinoshita, Shunya Nakayama, Hiroshi Koie

The red panda (Ailurus fulgens) can be found in zoos around the world, and various behavioral restraint procedures are used as part of their health care. Wild animals that are kept in zoos, including red pandas, are known to have a longer life span than those in the wild. Therefore, the health management of aging animals is considered especially important for zoos that maintain many precious wild animals. Blood pressure measurement is important for determining cardiovascular dynamics, however there are no reports of blood pressure measurements performed in red pandas without anesthesia. In this study, we measured blood pressure in four red pandas, over 4 years to establish a blood pressure measurement method using behavioral restraints. As a result, the blood pressure of red pandas was found to be similar to that of dogs and cats. In addition, in one case of red panda that evaluated high blood pressure during the measurement period, we added the antihypertensive drug and showed good effect for improvement of hypertension on long- term monitoring. Blood pressure values obtained using noninvasive methods were useful for red pandas. Moreover, these data were considered important for animal welfare.

世界各地的动物园中都有小熊猫(Ailurus fulgens)的踪迹,各种行为约束程序被用作小熊猫健康护理的一部分。众所周知,动物园中饲养的野生动物(包括小熊猫)的寿命比野外饲养的动物要长。因此,对于饲养许多珍贵野生动物的动物园来说,对衰老动物的健康管理尤为重要。血压测量对于确定心血管动态非常重要,但目前还没有关于小熊猫在不麻醉的情况下进行血压测量的报道。在这项研究中,我们对四只小熊猫进行了长达四年的血压测量,以建立一种使用行为约束的血压测量方法。结果发现,小熊猫的血压与狗和猫相似。此外,对一例在测量期间评估出高血压的小熊猫,我们添加了降压药物,并在长期监测中显示出改善高血压的良好效果。使用无创方法获得的血压值对小熊猫很有用。此外,这些数据对动物福利也很重要。
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引用次数: 0
Effects of low-level laser irradiation on canine fibroblasts. 低强度激光照射对犬成纤维细胞的影响
IF 1.1 4区 农林科学 Q3 VETERINARY SCIENCES Pub Date : 2024-11-13 DOI: 10.1292/jvms.24-0318
Melpa Susanti Purba, Dito Anggoro, Harumichi Itoh, Kazuhito Itamoto, Yuki Nemoto, Munekazu Nakaichi, Hiroshi Sunahara, Kenji Tani

Low-level laser (LLL) therapy is a well-known noninvasive treatment that stimulates fibroblasts to improve wound healing. LLL can improve fibroblast proliferation and migration without causing toxicity. The present study aimed to evaluate the effects of two laser wavelengths at different irradiation times on canine fibroblasts. Fibroblasts were isolated from canine oral mucosa. After seeding for 24 hr, the fibroblasts were irradiated using the Erchonia®️ EVL dual-diode laser at wavelengths of 405 nm (5 mW) and 640 nm (7.5 mW) with irradiation times of 120, 360, and 1,800 sec. The proliferating and viability cells were evaluated 24 hr after laser irradiation. Wound closure rates were calculated at 0, 24, and 48 hr after laser irradiation. Parameters, including proliferation cell, cell viability, and cell migration, tended to be higher in the 360-sec group (405 nm) and 120-sec group (640 nm) than in other groups. Our findings suggest that LLL therapy at wavelengths of 405 and 640 nm with an irradiation time of 120-360 sec (0.26-0.51 J/cm2) can stimulate the proliferation and migration of canine fibroblasts. This finding may contribute to a better understanding of the beneficial role of LLL stimulation in canine wound healing.

低强度激光疗法(LLL)是一种众所周知的非侵入性疗法,它能刺激成纤维细胞,改善伤口愈合。低强度激光可促进成纤维细胞的增殖和迁移,且不会产生毒性。本研究旨在评估两种波长、不同照射时间的激光对犬成纤维细胞的影响。研究人员从犬口腔黏膜中分离出成纤维细胞。播种 24 小时后,使用 Erchonia®️ EVL 双二极管激光器照射成纤维细胞,波长分别为 405 纳米(5 毫瓦)和 640 纳米(7.5 毫瓦),照射时间分别为 120 秒、360 秒和 1,800 秒。激光照射 24 小时后,对增殖细胞和存活细胞进行评估。计算激光照射后 0、24 和 48 小时的伤口闭合率。360 秒组(405 纳米)和 120 秒组(640 纳米)的增殖细胞、细胞活力和细胞迁移等参数往往高于其他组。我们的研究结果表明,波长为 405 纳米和 640 纳米、照射时间为 120-360 秒(0.26-0.51 J/cm2)的 LLL 疗法可刺激犬成纤维细胞的增殖和迁移。这一发现有助于更好地了解 LLL 刺激在犬伤口愈合中的有益作用。
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引用次数: 0
A clinical case of enzootic bovine leukosis in a Holstein cow with minor clonality of B-cell in the peripheral blood. 一例荷斯坦奶牛感染牛白血病的临床病例,其外周血中的 B 细胞有轻微克隆现象。
IF 1.1 4区 农林科学 Q3 VETERINARY SCIENCES Pub Date : 2024-11-04 DOI: 10.1292/jvms.24-0298
Masaki Maezawa, Misato Kikuzawa, Asahi Takiguchi, Ryo Saito, James K Chambers, Kazuyuki Uchida, Hisashi Inokuma

A 4-year 9-month-old Holstein-Friesian dairy cow presented with anorexia. On physical examination, swelling of superficial lymph nodes, pelvic masses, and prolonged urination posture after urinating a small amount were noted. Hematological examination revealed no lymphocytosis. The bovine leukemia virus proviral load was relatively high. At necropsy, enlarged lymph nodes, a large mass in the pelvic cavity, and mass lesions in several organs were observed. Histopathological examination revealed the proliferation of neoplastic lymphocytes, which were immune-positive for CD79α and negative for CD3. B-cell clonality test indicated the presence of monoclonality in the urine, masses, and lymph nodes and minor clonality in the peripheral blood. These findings led to a diagnosis of EBL with minor clonality of B-cell in the peripheral blood.

一头 4 岁 9 个月大的荷斯坦-弗里斯兰奶牛出现厌食症。体格检查时发现浅表淋巴结肿大、骨盆肿块以及少量排尿后排尿姿势延长。血液检查未发现淋巴细胞增多。牛白血病病毒载量相对较高。尸体解剖时,观察到淋巴结肿大、盆腔内有一巨大肿块以及多个器官的肿块病变。组织病理学检查显示肿瘤性淋巴细胞增生,CD79α免疫阳性,CD3阴性。B 细胞克隆检测显示,尿液、肿块和淋巴结中存在单克隆,外周血中存在少量克隆。这些结果导致了 EBL 和外周血中 B 细胞小克隆的诊断。
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引用次数: 0
A clinical case of B-cell lymphoma in a Japanese Black cow with monoclonal proliferation of B-cells as revealed by polymerase chain reaction based on the immunoglobulin light chain gene. 基于免疫球蛋白轻链基因的聚合酶链反应揭示的日本黑牛 B 细胞淋巴瘤单克隆增殖临床病例。
IF 1.1 4区 农林科学 Q3 VETERINARY SCIENCES Pub Date : 2024-11-04 DOI: 10.1292/jvms.24-0320
Tatsuki Nagata, Toshiyuki Harada, Masaki Maezawa, James K Chambers, Kazuyuki Uchida, Hisashi Inokuma

A 35-month-old Japanese Black cow was presented to a local veterinarian with a main complaint of premature labor. There was no swelling of lymph nodes on the body surface and no palpable mass on rectal examination. Although atypical lymphocytes were observed in the peripheral blood, no lymphocytosis was recorded. On Day 12, the cow developed hindlimb paresis and was euthanized. Necropsy revealed swelling of some lymph nodes, and white nodules in uterus and right atrial appendage. Histopathological examination revealed B-cell lymphoma. In clonality analysis of peripheral blood and tumor tissue, monoclonal proliferation was detected by PCR for immunoglobulin light chain (IgL) λ, suggesting neoplastic proliferation of B-cell. IgL-PCR is thought to be a possible tool for diagnosis of B-cell lymphoma.

一头 35 个月大的日本黑牛主诉早产,被送往当地一家兽医诊所。体表无淋巴结肿大,直肠检查也未触及肿块。虽然在外周血中观察到非典型淋巴细胞,但未记录到淋巴细胞增多。第 12 天,母牛后肢瘫痪,被实施安乐术。剖检发现一些淋巴结肿大,子宫和右心房阑尾有白色结节。组织病理学检查显示为 B 细胞淋巴瘤。在外周血和肿瘤组织的克隆分析中,通过免疫球蛋白轻链(IgL)λ的PCR检测发现了单克隆增殖,提示B细胞肿瘤性增殖。IgL-PCR被认为是诊断B细胞淋巴瘤的一种可能工具。
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引用次数: 0
A case of hydronephrosis due to intrarenal ureteral obstruction in a Japanese Black calf. 日本黑小牛肾内输尿管梗阻导致肾积水的病例。
IF 1.1 4区 农林科学 Q3 VETERINARY SCIENCES Pub Date : 2024-11-01 Epub Date: 2024-09-27 DOI: 10.1292/jvms.24-0173
Reiichiro Sato, Takuya Hirai, Asmaa A Hegazy, Mutsumi Nakai, Yukiko Sato, Kazutaka Yamada, Hiroyuki Satoh, Adrian Steiner

A 23-day-old Japanese Black female calf presented with distension of the lower abdomen. Abdominal ultrasonography revealed a cystic structure with fluid accumulation and moderate echoluminance in the right abdominal cavity. Ultrasonography and contrast-enhanced computed tomography revealed congenital hydronephrosis due to narrowing of the intrarenal ureter, and right kidney resection was performed. Blood urea nitrogen and serum creatinine levels, which were within reference values preoperatively, peaked on the third postoperative day and gradually decreased afterward until reaching preoperative values on the tenth day. In bovine hydronephrosis, nephrectomy may provide a favorable prognosis if one kidney is intact. Moreover, this case suggests that blood tests immediately after surgery are not suitable for evaluating residual kidneys.

一头 23 天大的日本黑雌性小牛因下腹部胀痛就诊。腹部超声波检查发现右腹腔内有一个积液的囊性结构,回声中等。超声波检查和造影剂增强计算机断层扫描显示,肾内输尿管狭窄导致先天性肾积水,于是进行了右肾切除术。术前血尿素氮和血清肌酐水平在参考值范围内,术后第三天达到峰值,之后逐渐下降,直到第十天达到术前水平。对于牛肾积水,如果一侧肾脏完好,肾切除术可能会带来良好的预后。此外,本病例表明,术后立即进行血液检测并不适合评估残余肾脏。
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引用次数: 0
Differences in antimicrobial resistance-related genes of Trueperella pyogenes between isolates detected from cattle and pigs. 从牛和猪中检测到的化脓性真菌抗菌药耐药性相关基因的差异。
IF 1.1 4区 农林科学 Q3 VETERINARY SCIENCES Pub Date : 2024-11-01 Epub Date: 2024-09-19 DOI: 10.1292/jvms.24-0180
Hideki Fujimoto, Natsuki Shimoji, Tatsumi Sunagawa, George Sanga, Takehisa Chuma

We investigated antimicrobial resistance-related genes in 109 isolates of Trueperella pyogenes that were isolated in cattle and pigs. All 89 tetracycline-resistant T. pyogenes isolates carried the resistance gene harbored either tetW, tetM, tetA(33), tetK, or tetL. The ermX or ermB were detected in 18 of 23 erythromycin-resistant isolates. Streptomycin-resistant aadA1, aadA9, aadA11, aadA24, strA, or strB were detected in 25 of 83 isolates. There were significant differences in the percentages of tetA(33), ermB, aadA1, aadA9, aadA11, or aadA24 carriage between cattle and pig isolates. In addition, the Class 1 gene cassette was detected only in 17 cattle isolates. This suggests that T. pyogenes isolates acquire resistance gene in each environment of cattle and pigs, and that the transmission of the bacteria between cattle and pigs is limited.

我们调查了从牛和猪体内分离出的 109 株化脓性特雷伯氏菌的抗菌药耐药性相关基因。所有 89 个耐四环素的化脓性真菌分离株都携带耐药基因 tetW、tetM、tetA(33)、tetK 或 tetL。在 23 个耐红霉素的分离株中,有 18 个检测到了 ermX 或 ermB。83 个分离株中有 25 个检测到了耐链霉素的 aadA1、aadA9、aadA11、aadA24、strA 或 strB。牛和猪分离物携带 tetA(33)、ermB、aadA1、aadA9、aadA11 或 aadA24 的百分比有明显差异。此外,仅在 17 个牛分离物中检测到 1 类基因盒。这表明,化脓性梭菌分离物在牛和猪的不同环境中都能获得抗性基因,牛和猪之间的细菌传播是有限的。
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引用次数: 0
Preclinical/clinical trials of thrice-weekly administration of a combination of tegafur/gimeracil/oteracil (TS-1) and toceranib phosphate in dogs with intranasal tumors. 对患有鼻内肿瘤的狗每周三次服用替加氟/吉莫拉嘧啶/奥替拉西尔(TS-1)和磷酸托塞拉尼组合物的临床前/临床试验。
IF 1.1 4区 农林科学 Q3 VETERINARY SCIENCES Pub Date : 2024-11-01 Epub Date: 2024-10-03 DOI: 10.1292/jvms.23-0455
Yuta Nishiyama, Takuya Maruo, Yasuhiro Fukuyama, Yuka Odaka, Eiyu Kawata, Hirona Ueno, Hideki Kayanuma, Tomohiro Nakayama, Hiroki Takahashi

Intranasal tumors in dogs are malignant solid tumors that are primarily treated with radiotherapy and often recur post-treatment. Combination therapy is pivotal in cancer therapy. Effective drugs include fluoropyrimidine 5-fluorouracil (5-FU) and toceranib phosphate. TS-1, an oral formulation containing the 5-FU prodrug tegafur and enzyme modulators gimeracil and oteracil, is proven to be safe in dogs with solid tumors. While the oral drug toceranib phosphate (Palladia®) is safely administered, the combined toxicity with TS-1 is unknown. We aimed to determine the dosage of this combination in dogs. In the preclinical/clinical trials conducted here, we used a standard 3+3 cohort design with fixed doses of toceranib phosphate (2.4 mg/kg) administered thrice weekly. TS-1 administration was initiated at a dose of 0.5 mg/kg (upper limit 2.0 mg/kg) thrice weekly. Four cohorts were included to confirm the safety of TS-1 and toceranib phosphate. Each cohort was followed up for 1 month. The intranasal tumor types included in the clinical trial (n=13) were adenocarcinoma (n=7), squamous cell carcinoma (n=1), non-epithelial malignancy (n=2), undifferentiated carcinoma (n=1), and transitional carcinoma (n=2). The TS-1 dosage could be increased up to its dose limit in the preclinical/clinical trials. The TS-1 dose to combine with toceranib phosphate thrice weekly was 2.0 mg/kg. This regimen was well-tolerated in dogs. Thus, combined TS-1 and toceranib phosphate therapy is safe for dogs with intranasal tumors.

犬鼻腔内肿瘤属于恶性实体肿瘤,主要采用放射治疗,治疗后经常复发。联合疗法在癌症治疗中举足轻重。有效的药物包括氟嘧啶-5-氟尿嘧啶(5-FU)和磷酸托塞拉尼。TS-1 是一种口服制剂,含有 5-FU 原药替加氟(tegafur)和酶调节剂吉美拉嘧啶(gimeracil)和奥特拉嘧啶(eteracil),经证实对患有实体瘤的狗是安全的。虽然口服药物磷酸托塞拉尼(Palladia®)用药安全,但与 TS-1 的联合毒性尚不清楚。我们的目标是确定这种联合用药在狗体内的剂量。在这里进行的临床前/临床试验中,我们采用了标准的 3+3 队列设计,每周三次给药固定剂量的磷酸托塞瑞尼(2.4 毫克/千克)。TS-1的给药剂量为0.5 mg/kg(上限为2.0 mg/kg),每周三次。为确认 TS-1 和磷酸托塞拉尼的安全性,共纳入了四个队列。每个组群的随访时间为 1 个月。纳入临床试验的鼻内肿瘤类型(n=13)包括腺癌(n=7)、鳞癌(n=1)、非上皮恶性肿瘤(n=2)、未分化癌(n=1)和过渡性癌(n=2)。在临床前/临床试验中,TS-1 的剂量可增加到其剂量极限。TS-1与磷酸托塞瑞尼每周三次的联合用药剂量为2.0毫克/千克。狗对这一治疗方案的耐受性良好。因此,TS-1和磷酸托塞瑞尼联合疗法对患有鼻内肿瘤的狗是安全的。
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Journal of Veterinary Medical Science
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