著者

Satoshi KAMBAYASHI Masaya IGASE Kosuke KOBAYASHI Ayana KIMURA Takako SHIMOKAWA-MIYAMA Kenji BABA Shunsuke NOGUCHI Takuya MIZUNO Masaru OKUDA

出版者

公益社団法人 日本獣医学会

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

pp.15-0258, (Released:2015-06-06)

被引用文献数

1 12

---

Hypoxic conditions in various cancers are believed to relate with their malignancy, and hypoxia inducible factor-1α (HIF-1α) has been shown to be a major regulator of the response to low oxygen. In this study, we examined HIF-1α expression in canine lymphoma using cell lines and clinical samples and found that these cells expressed HIF-1α. Moreover, the HIF-1α inhibitors, echinomycin, YC-1 and 2-methoxyestradiol, suppressed the proliferation of canine lymphoma cell lines. In a xenograft model using NOD/scid mice, echinomycin treatment resulted in a dose-dependent regression of the tumor. Our results suggest that HIF-1α contributes to the proliferation and/or survival of canine lymphoma cells. Therefore, HIF-1α inhibitors may be potential agents to treat canine lymphoma.

著者

Masaya IGASE Chung Chew HWANG Matt COFFEY Masaru OKUDA Shunsuke NOGUCHI Takuya MIZUNO

出版者

公益社団法人 日本獣医学会

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

pp.14-0570, (Released:2015-01-16)

被引用文献数

1 12

---

Oncolytic virotherapy is a new strategy for cancer treatment for humans and dogs. Reovirus has been proven to be a potent oncolytic virus in human medicine. Our laboratory has previously reported that canine mast cell tumor and canine lymphoma were susceptible to reovirus. In this study, canine solid tumor cell lines (mammary gland tumor, osteosarcoma and malignant melanoma) were tested to determine their susceptibility towards reovirus. We demonstrated that reovirus induces more than 50% cell death in three canine mammary gland tumors and one canine malignant melanoma cell line. The reovirus-induced cell death occurred via the activation of caspase 3. Ras activation has been shown to be one of the important mechanisms of reovirus-susceptibility in human cancers. However, Ras activation was not related to the reovirus-susceptibility in canine solid tumor cell lines, which was similar to reports in canine mast cell tumor and canine lymphoma. The results of this study highly suggest that canine mammary gland tumor and canine malignant melanoma are also potential candidates for reovirus therapy in veterinary oncology.

著者

Yuki NEMOTO Tomoya HARAGUCHI Takako SHIMOKAWA MIYAMA Kosuke KOBAYASHI Kaori HAMA Yosuke KUROGOUCHI Noriyuki FUJIKI Kenji BABA Masaru OKUDA Takuya MIZUNO

出版者

公益社団法人 日本獣医学会

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

pp.17-0026, (Released:2017-05-22)

被引用文献数

9

---

A 16-year-old spayed female American Shorthair cat was presented with lethargy, anorexia, and wamble. Physical and blood examination did not reveal any remarkable findings. Abdominal ultrasonography identified the presence of a localized anechoic structure with a thick wall in contact with the small intestine and adjacent to the liver. Ultrasound-guided fine-needle aspiration of the structure revealed fluid containing numerous cocci and neutrophils. Two days after antibiotic treatment, exploratory laparotomy was performed and the content of the structure was removed before multiple lavages. The pathological and bacteriological examination results supported a confirmatory diagnosis of pancreatic abscess due to Staphylococcus aureus infection, making this the first such report in a cat. The cat remained healthy thereafter with no disease recurrence.

著者

Shuhei ENJOJI Ryotaro YABE Nobuyuki FUJIWARA Shunya TSUJI Michael P. VITEK Takuya MIZUNO Takayuki NAKAGAWA Tatsuya USUI Takashi OHAMA Koichi SATO

出版者

公益社団法人 日本獣医学会

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

pp.15-0193, (Released:2015-06-11)

被引用文献数

2 16

---

Canine melanoma is one of the most important diseases in small animal medicine. Protein phosphatase 2A (PP2A), a well conserved serine/threonine phosphatase, plays a critical role as a tumor suppressor. SET/I2PP2A is an endogenous inhibitor for PP2A, which directly binds to PP2A and suppresses its phosphatase activity. Elevated SET protein levels have been reported to exacerbate human tumor progression. The role of SET in canine melanoma, however, has not been understood. Here, we investigated the potential therapeutic role for SET inhibitors in canine melanoma. The expression of SET protein was observed in 6 canine melanoma cell lines. We used CMeC-1 cells (primary origin) and CMeC-2 cells (metastatic origin) to generate cell lines stably expressing SET-targeting shRNAs. Knockdown of SET expression in CMeC-2, but not in CMeC-1, leads to decreased cell proliferation, invasion and colony formation. Phosphorylation level of p70 S6 kinase was decreased by SET knockdown in CMeC-2, suggesting the involvement of mTOR (mammalian target of rapamycin)/p70 S6 kinase signaling. The SET inhibitors, OP449 and FTY720, more effectively killed CMeC-2 than CMeC-1. We observed PP2A activation in CMeC-2 treated with OP449 and FTY720. These results demonstrated the potential therapeutic application of SET inhibitors for canine melanoma.

著者

Leni MAYLINA Satoshi KAMBAYASHI Kenji BABA Masaya IGASE Takuya MIZUNO Masaru OKUDA

出版者

JAPANESE SOCIETY OF VETERINARY SCIENCE

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

vol.85, no.1, pp.99-104, 2023 (Released:2023-01-20)

参考文献数

29

被引用文献数

1

---

Canine lymphoma/leukemia cell lines with p16 protein expressions: high (17–71 and GL-1) and low (CLBL-1, CLC, Nody-1, and UL-1) were treated in vitro with cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, palbociclib or abemaciclib. Cell proliferation decreased as a result, with higher IC50 levels observed in the high p16 (17–71 and GL-1) and one low p16 (UL-1) cell lines compared with the low p16 cells (CLBL-1, CLC, and Nody-1). As expected, palbociclib and abemaciclib treatment reduced pRb phosphorylation in a dose-dependent manner, especially in cells with low p16. These results suggest that CDK4/6 inhibitors have potential as new chemotherapeutic agents for canine lymphoma and high p16 protein expression may be used as a biomarker for resistance to CDK4/6 inhibitor therapy.

著者

Toshitaka KANEI Munetaka IWATA Hiroaki KAMISHINA Takuya MIZUNO Sadatoshi MAEDA

出版者

JAPANESE SOCIETY OF VETERINARY SCIENCE

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

vol.84, no.1, pp.25-30, 2022 (Released:2022-01-07)

参考文献数

24

---

C-C chemokine receptor 7 (CCR7) contributes to cell homing to lymph nodes (LNs). Recent studies reported that CCR7 is also expressed in tumor cells, which correlates with LN metastasis in various cancers. However, the expression of CCR7 in tumor cells is unknown in dogs due to the lack of appropriate antibodies. In the present study, a fusion protein of C-C chemokine ligand 19 (CCL19) was employed as an alternative method to CCR7 antibodies. The fusion CCL19 protein specifically detected CCR7 expressed in canine lymphoma cell lines, which showed active chemotaxis to both canine and mouse ligands. The present study will help further research on the involvement of canine CCR7 in LN metastasis.

著者

Masaya IGASE Yuki MORINAGA Masahiro KATO Toshihiro TSUKUI Yusuke SAKAI Masaru OKUDA Takuya MIZUNO

出版者

JAPANESE SOCIETY OF VETERINARY SCIENCE

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

pp.19-0667, (Released:2020-03-06)

被引用文献数

1

---

DEP domain-containing 1B (DEPDC1B) is involved in the regulation of cell de-adhesion and actin cytoskeleton activity during the G2/M transition of the cell cycle, and its overexpression has been proven to be associated with cancer progression in several human cancers. Canine DEPDC1B was identified as a gene that was overexpressed in canine lymphoma tissues in our previous study. However, in dogs, the protein expression of DEPDC1B remains to be determined due to the lack of a specific monoclonal antibody. Here, we developed rat monoclonal antibodies against canine DEPDC1B and characterized their applicability for immunodetection assays. Our findings demonstrated that these antibodies are functional and can be important tools to investigate the precise role of DEPDC1B in canine tumors.

著者

Kosuke KOBAYASHI Kenji BABA Masaya IGASE Hardany PRIMARIZKY Yuki NEMOTO Takako SHIMOKAWA MIYAMA Satoshi KAMBAYASHI Takuya MIZUNO Masaru OKUDA

出版者

JAPANESE SOCIETY OF VETERINARY SCIENCE

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

pp.19-0400, (Released:2019-10-15)

被引用文献数

2

---

Hypercoagulability is a common paraneoplastic complication in dogs with various malignant tumors. Importantly, tissue factor procoagulant activity (TF-PCA) induced by TF-bearing microparticles (TF-MPs) is associated with hypercoagulability in human patients with cancer. However, TF-PCA in tumor cells and the association between circulating TF-MPs and hypercoagulability in dogs with malignant tumors remain poorly understood. Therefore, the present study was conducted to evaluate the TF-PCA in various types of canine tumor cell lines and plasma in dogs with malignant tumors. Mammary gland tumor, hemangiosarcoma, and malignant melanoma cell lines, but not lymphoma cell lines, expressed TF on their surfaces and showed cellular surface and MP-associated TF-PCA. The plasma TF-PCA was elevated in some dogs that naturally developed such tumors. No significant difference was observed in plasma TF-PCA between the disseminated intravascular coagulation (DIC) group (median: 43.40; range: 3.47–85.19; n=5) and non-DIC group (median: 7.73; range: 1.70–16.13; n=12). However, plasma TF-PCA was remarkably elevated in three of five dogs with DIC. To the best of our knowledge, this is the first study to evaluate plasma TF-PCA in dogs with malignant tumors. Further studies must be conducted to determine the cellular origin of TF-MPs and the efficacy of plasma TF-PCA as a biomarker of DIC in dogs with malignant tumors.

著者

Yuki NEMOTO Tomoya HARAGUCHI Takako SHIMOKAWA MIYAMA Kosuke KOBAYASHI Kaori HAMA Yosuke KUROGOUCHI Noriyuki FUJIKI Kenji BABA Masaru OKUDA Takuya MIZUNO

出版者

公益社団法人 日本獣医学会

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

vol.79, no.7, pp.1146-1150, 2017 (Released:2017-07-07)

参考文献数

17

被引用文献数

9

---

A 16-year-old spayed female American Shorthair cat was presented with lethargy, anorexia, and wamble. Physical and blood examination did not reveal any remarkable findings. Abdominal ultrasonography identified the presence of a localized anechoic structure with a thick wall in contact with the small intestine and adjacent to the liver. Ultrasound-guided fine-needle aspiration of the structure revealed fluid containing numerous cocci and neutrophils. Two days after antibiotic treatment, exploratory laparotomy was performed and the content of the structure was removed before multiple lavages. The pathological and bacteriological examination results supported a confirmatory diagnosis of pancreatic abscess due to Staphylococcus aureus infection, making this the first such report in a cat. The cat remained healthy thereafter with no disease recurrence.

著者

Osamu SAKAI Masashi SAKURAI Hiroki SAKAI Masahito KUBO Hiroko HIRAOKA Kenji BABA Masaru OKUDA Takuya MIZUNO

出版者

公益社団法人 日本獣医学会

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

pp.17-0229, (Released:2017-06-12)

被引用文献数

5

---

Wilms’ tumor 1 (WT1) expression has been investigated in various human cancers as a target molecule for cancer immunotherapy. However, few studies have focused on WT1 expression in dogs. Firstly, cDNA of canine WT1 (cWT1) was molecularly cloned from normal canine kidney. The cross-reactivity of the anti-human WT1 monoclonal antibody (6F-H2) with cWT1 was confirmed via Western blotting using cells overexpressing cWT1. Immunohistochemical staining revealed that cWT1 expression was detected in all canine lymphoma tissues and in some normal canine tissues, including the kidney and lymph node. cWT1 is a potential immunotherapy target against canine cancers.

著者

Kosuke KOBAYASHI Takako SHIMOKAWA MIYAMA Kazuhito ITAMOTO Shunsuke NOGUCHI Kenji BABA Takuya MIZUNO Masaru OKUDA

出版者

公益社団法人 日本獣医学会

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

pp.16-0019, (Released:2016-06-20)

被引用文献数

2

---

A 2-year-old female beagle was referred to our hospital for evaluation of anemia. Laboratory tests, including bone marrow cytology, revealed non-regenerative immune-mediated anemia (NRIMA). Although initial immunosuppressive multi-drug therapy was not effective, additional administration of danazol was successful in treating the anemia. However, hepatocellular carcinoma (HCC) developed about 20 months after the administration of danazol. In humans, several cases of development of HCC after the administration of danazol have been reported. The present report describes a case of HCC development in a dog after chronic administration of danazol in addition to other immunosuppressive drugs.

著者

Koji KAWANO Hidekatsu SHIMAKURA Noriyuki NAGATA Yuki MASASHI Akemi SUTO Yukinori SUTO Shohei UTO Hiromichi UENO Takehiro HASEGAWA Takahiro USHIGUSA Takashi NAGAI Yasunori ARAWATARI Kazuki MIYAJI Keitaro OHMORI Takuya MIZUNO

出版者

公益社団法人 日本獣医学会

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

pp.15-0457, (Released:2016-05-05)

被引用文献数

14

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There have been limited reports on the prevalence of adverse food reactions among dogs suffering from chronic enteropathy (CE) in Japan. We examined the prevalence and histological features of food-responsive enteropathy (FRE) in a total of 32 dogs with history of CE. Fourteen of 18 cases (56.2%) diagnosed as FRE had lymphocytic-plasmacytic enteritis or eosinophilic enteritis by histopathological examination. Characteristic histopathological changes indicating FRE were not identified in 18 cases, though 4 cases did not show any abnormalities. Results collected from this study provided important information that can help to change the way dogs with CE are treated in the future.

著者

Masaya IGASE Takako SHIMOKAWA MIYAMA Satoshi KAMBAYASHI Yumiko SHIMOYAMA Hiroko HIRAOKA Yumi HIRATA Miki IWATA Kenji BABA Takuya MIZUNO Masaru OKUDA

出版者

公益社団法人 日本獣医学会

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

pp.15-0156, (Released:2015-12-04)

被引用文献数

7

---

A 10-year-old female spayed mixed breed cat with a subcutaneous mass on the right hind limb-was revealed with bimodal monoclonal gammopathy composed of IgA by immunoelectrophoresis and immunofixation. Approximately 1 month after referral, the cat died due to renal failure. Postmortem immunohistopathologic evaluation of the subcutaneous mass revealed neoplastic cell proliferation of plasma cells and giant myeloma cells. Neoplastic cells were also present in the liver and spleen. These results led to the diagnosis of a rare case of feline myeloma-related disorders with extramedullary plasmacytoma infiltrating in multiple locations. This report emphasizes the necessity to accumulate cases with similar clinicopathologic findings in the future.

著者

Ryotaro YABE Nobuyuki FUJIWARA Takuya MIZUNO Tatsuya USUI Takashi OHAMA Koichi SATO

出版者

公益社団法人 日本獣医学会

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

pp.14-0209, (Released:2014-06-03)

被引用文献数

1 5

---

SET is an endogenous protein phosphatase 2A (PP2A) inhibitor and is associated with a poor prognosis in human leukemia. Previously, we reported increased SET protein levels in canine lymphoma cell lines and the potential therapeutic application of SET antagonists in canine lymphoma. Here, we found that canine cells express several isoforms of the SET protein. We cloned four isoforms of SET, named SETα, β, γ and δ. Genomic BLAST showed that the SET genes are located on chromosomes X, 7, 1 and 8, respectively. An immunofluorescent study showed nuclear localization of SETα and β, and nuclear and cytosolic localization of SETγ and δ. We confirmed that SETα and β possess the ability to associate with PP2A. Our data reveal the existence of unique SET isoforms that should be taken into account in SET-targeting drug development studies in dogs.

著者

Hiroto TOYODA Akiyoshi TANI Yuko GOTO-KOSHINO Tomoki MOTEGI Mika SAKAMOTO Takako MOCHIZUKI Kei HARADA Tetsuya KOBAYASHI Asuka SETOGUCHI Yohei SHIZUTA Takuya MIZUNO Mitsuhiro IRIE Jun NAKAMICHI Hajime TSUJIMOTO Aki OHMI Ray FUKUOKA Yasukazu NAKAMURA Hirotaka TOMIYASU

出版者

JAPANESE SOCIETY OF VETERINARY SCIENCE

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

vol.86, no.1, pp.18-27, 2024 (Released:2024-01-10)

参考文献数

49

被引用文献数

1

---

Although chemotherapy using CHOP-based protocol induces remission in most cases of canine multicentric high-grade B-cell lymphoma (mhBCL), some cases develop early relapse during the first induction protocol. In this study, we examined the gene expression profiles of canine mhBCL before chemotherapy and investigated their associations with early relapse during the first whole CHOP-based protocol. Twenty-five cases of mhBCL treated with CHOP-based protocol as first induction chemotherapy were included in this study. Sixteen cases completed the first whole CHOP-based protocol without relapse (S-group), and nine developed relapse during the chemotherapy (R-group). RNA-seq was performed on samples from neoplastic lymph nodes. Differentially expressed genes (DEGs) were extracted by the comparison of gene expression profiles between S- and R-groups, and the differences in the expression levels of these genes were validated by RT-qPCR. Extracted 179 DEGs included the genes related to chemokine CC motif ligand, T-cell receptor signaling pathway, and PD-L1 expression and PD-1 checkpoint pathway. We focused on chemokine CC motif ligand, and CCL4 was confirmed to be significantly downregulated in the R-group (P=0.039). We also focused on the genes related to T-cell signaling pathway, and CD3E (P=0.039), ITK (P=0.023), and LAT (P=0.023) genes were confirmed to be significantly upregulated in the R-group. The current results suggest that both changes in tumor cells and the interactions between tumor cells and immune cells are associated with the efficacy of the chemotherapy for first remission induction.

著者

Hiroto TOYODA Akiyoshi TANI Yuko GOTO-KOSHINO Tomoki MOTEGI Mika SAKAMOTO Takako MOCHIZUKI Kei HARADA Tetsuya KOBAYASHI Asuka SETOGUCHI Yohei SHIZUTA Takuya MIZUNO Mitsuhiro IRIE Jun NAKAMICHI Hajime TSUJIMOTO Aki OHMI Ray FUKUOKA Yasukazu NAKAMURA Hirotaka TOMIYASU

出版者

JAPANESE SOCIETY OF VETERINARY SCIENCE

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

pp.23-0269, (Released:2023-11-13)

被引用文献数

1

---

Although chemotherapy using CHOP-based protocol induces remission in most cases of canine multicentric high-grade B-cell lymphoma (mhBCL), some cases develop early relapse during the first induction protocol. In this study, we examined the gene expression profiles of canine mhBCL before chemotherapy and investigated their associations with early relapse during the first whole CHOP-based protocol. Twenty-five cases of mhBCL treated with CHOP-based protocol as first induction chemotherapy were included in this study. Sixteen cases completed the first whole CHOP-based protocol without relapse (S-group), and nine developed relapse during the chemotherapy (R-group). RNA-seq was performed on samples from neoplastic lymph nodes. Differentially expressed genes (DEGs) were extracted by the comparison of gene expression profiles between S- and R-groups, and the differences in the expression levels of these genes were validated by RT-qPCR. Extracted 179 DEGs included the genes related to chemokine CC motif ligand, T-cell receptor signaling pathway, and PD-L1 expression and PD-1 checkpoint pathway. We focused on chemokine CC motif ligand, and CCL4 was confirmed to be significantly downregulated in the R-group (P=0.039). We also focused on the genes related to T-cell signaling pathway, and CD3E (P=0.039), ITK (P=0.023), and LAT (P=0.023) genes were confirmed to be significantly upregulated in the R-group. The current results suggest that both changes in tumor cells and the interactions between tumor cells and immune cells are associated with the efficacy of the chemotherapy for first remission induction.

著者

Hiroka YAMAMOTO Kyoga KIMURA Hiro HORIKIRIZONO Yojiro TAMURA Satoshi KAMBAYASHI Kenji BABA Masaru OKUDA Takuya MIZUNO Masaya IGASE

出版者

JAPANESE SOCIETY OF VETERINARY SCIENCE

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

pp.23-0243, (Released:2023-08-16)

---

A 1-year-old spayed female Miniature Schnauzer had chronic hyponatremia, accompanied by polyuria and polydipsia. Blood tests and urinalysis revealed severe hyponatremia, low plasma osmolality with euvolemia, and increased sodium excretion in urine. Hypothyroidism and hypoadrenocorticism were ruled out as causes. These findings led to the diagnosis of syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Magnetic resonance imaging (MRI) showed dilation of the lateral ventricles, indicating severe hydrocephalus. Tolvaptan, a vasopressin V2 receptor antagonist commonly used in human SIADH, was administered along with water restriction. This treatment resulted in a consistent increase in plasma sodium levels without any adverse effects. This case report represents the first documented evidence of the therapeutic efficacy of tolvaptan in treating SIADH in a dog.

著者

Shoma NISHIBORI Masashi SAKURAI Yumiko KAGAWA Kazuyuki UCHIDA Takayuki NAKAGAWA Masaya IGASE Takuya MIZUNO

出版者

JAPANESE SOCIETY OF VETERINARY SCIENCE

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

vol.85, no.6, pp.592-600, 2023 (Released:2023-06-01)

参考文献数

45

被引用文献数

1

---

Immunotherapy is a breakthrough in human cancer therapy and has become a major concern in veterinary oncology. However, in cats, many unclear points of the tumor microenvironment exist, including immune checkpoint molecules. A reason is that very few monoclonal antibodies have been proven to react with feline molecules. Therefore, this study investigated whether anti-human programmed cell death ligand 1 (PD-L1) monoclonal antibody, clone 28-8, which is currently commercially available, can also recognize feline PD-L1 by flow cytometry, immunoprecipitation, and immunohistochemical (IHC) staining. We confirmed that the antibody’s specificity by flow cytometry and immunoprecipitation using NIH3T3 cells transfected with feline PD-L1. Additionally, we revealed that PD-L1 was expressed on the surface of some feline cell lines by flow cytometry and clone 28-8 antibody unbound to the cells where feline PD-L1 was knocked out. Furthermore, IHC analysis revealed that PD-L1 was expressed in macrophages in the spleen and lymph nodes from healthy cats and mast cell tumor cells. Therefore, we indicated that the clone 28-8 antibody is a valuable tool in detecting feline PD-L1, and further analysis of tumor tissues is expected in the future.

著者

Miki SUEMURA Haruki MIYATA Rio KAWAMURA Sho TAKAHASHI Masaya IGASE Takuya MIZUNO Takashi OHAMA Shusaku SHIBUTANI Hiroyuki IWATA

出版者

JAPANESE SOCIETY OF VETERINARY SCIENCE

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

pp.23-0036, (Released:2023-07-04)

---

Canine lymphoma is the most common cancer in dogs and has a poor prognosis. We recently found that the endocytosis inhibitor dynasore suppresses the viability of human cancer cell lines, especially hematopoietic cancers, by inducing apoptosis. In the present study, we examined the anticancer effects of dynasore on five previously established canine lymphoma cell lines (CLBL-1, Ema, Nody-1, CLC, and GL-1). Dynasore suppressed cell viability in these canine lymphoma cell lines more effectively than in human cancer cell lines. It also induced apoptosis in CLBL-1 and Ema cells but not in peripheral blood mononuclear cells in healthy dogs or in Madin-Darby canine kidney (MDCK) cells, suggesting that the ability of dynasore to induce apoptosis is cancer-specific. Furthermore, dynasore induced a DNA damage response in CLBL-1 and Ema cells, suggesting that it acts as a genotoxic agent in canine lymphoma cell lines. These findings suggest that endocytosis inhibitors may provide a new anticancer treatment for canine lymphoma.

著者

Leni MAYLINA Satoshi KAMBAYASHI Kenji BABA Masaya IGASE Takuya MIZUNO Masaru OKUDA

出版者

JAPANESE SOCIETY OF VETERINARY SCIENCE

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

pp.22-0498, (Released:2022-11-29)

被引用文献数

1

---

Canine lymphoma/leukemia cell lines with p16 protein expressions: high (17-71 and GL-1) and low (CLBL-1, CLC, Nody-1, and UL-1) were treated in vitro with cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, palbociclib or abemaciclib. Cell proliferation decreased as a result, with higher IC50 levels observed in the high p16 (17-71 and GL-1) and one low p16 (UL-1) cell lines compared with the low p16 cells (CLBL-1, CLC, and Nody-1). As expected, palbociclib and abemaciclib treatment reduced pRb phosphorylation in a dose-dependent manner, especially in cells with low p16. These results suggest that CDK4/6 inhibitors have potential as new chemotherapeutic agents for canine lymphoma and high p16 protein expression may be used as a biomarker for resistance to CDK4/6 inhibitor therapy.