著者

Kosei SAKAI Tomohiro YONEZAWA Hideyuki YAMAWAKI Toshifumi OYAMADA

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.15-0002, (Released:2015-05-18)

被引用文献数

1 4

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Somatostatin receptor 2 (SSTR2) is a negative regulator of cell proliferation in human breast cancer. Since there is little information about SSTR2 in canine mammary gland tumor (MGT), we clarified its distribution and expression level in normal mammary gland, benign MGT and malignant MGT. SSTR2 expression determined by immunohistochemical staining was observed in the cytoplasm of luminal epithelial cells. The intensity was negatively correlated with malignancy: normal tissues and some of the benign tumors had the highest levels, while the malignant tumors had little or no SSTR2 expression. As for the Western blotting, SSTR2 protein level in benign tumors was significantly lower than the normal mammary gland. On the other hand, SSTR2 protein levels in two of three malignant tumors were higher than the other groups. These results suggest that SSTR2 expression alters according to the malignancy of canine MGT.

著者

Giulianne C. CROCIOLLI Renata N. CASSU Rafael C. BARBERO Thalita L.A ROCHA Denis R. GOMES Gabriel M. NICÁCIO

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.14-0602, (Released:2015-03-29)

被引用文献数

4 36

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This study aimed to evaluate the analgesic efficacy of gabapentin as an adjuvant for postoperative pain management in dogs. Twenty dogs undergoing mastectomy were randomized to receive perioperative oral placebo or gabapentin (10 mg/kg). All dogs were premedicated with intramuscular acepromazine (0.03 mg/kg) and morphine (0.3 mg/ kg). Anesthesia was induced with propofol (4 mg/kg) intravenously and maintained with isoflurane. Intravenous meloxicam (0.2 mg/kg) was administered preoperatively. Postoperative analgesia was evaluated for 72 hr. Rescue analgesia was provided with intramuscular morphine (0.5 mg/kg). Dogs in the Placebo group received significantly more morphine doses than the Gabapentin group (P=0.021) despite no significant differences in pain scores. Perioperative gabapentin reduced the postoperative morphine requirements in dogs after mastectomy.

著者

Juyeon OH Ju-hwan LEE Kyoung-oh CHO Jihye CHOI

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.14-0115, (Released:2015-01-10)

被引用文献数

1 2

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This report described radiographic and CT features of atypical diffuse idiopathic skeletal hyperostosis in a 5-year-old, female Shih-tzu showing marked proliferative bone lesions in the appendicular skeleton with minor spinal changes. Continuous or flowing bony bridge formation of vertebrae is used as the gold standard for diagnosing diffuse idiopathic skeletal hyperostosis. However, this criterion seems not to be suitable for appendicular type diffuse idiopathic skeletal hyperostosis, as in the present case. Diffuse idiopathic skeletal hyperostosis is a progressive skeletal disease, and thus, enthesophysis and the multiple bony proliferations at insertion sites of ligaments and tendons to appendicular bones in a lamellar or trabecular pattern were considered diagnostic features of the appendicular type of diffuse idiopathic skeletal hyperostosis.

著者

Yusuke IZUMI Yuki HOSHINO Kenji HOSOYA Satoshi TAKAGI Masahiro OKUMURA

出版者

JAPANESE SOCIETY OF VETERINARY SCIENCE

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

pp.14-0347, (Released:2014-12-05)

被引用文献数

1 2

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The present study involved the isolation and characterization of canine tumor endothelial cells (TECs) from two malignancies. TECs were isolated using magnetic cell sorting following FITC labeling with UEA1 lectin, and they were characterized by measuring genetic and histopathological endothelial markers. Isolated TECs exhibited a cobblestone-like morphology and expressed both vascular endothelial growth factor receptor 2 (VEGFR2) and Von Willebrand factor (vWF). Further, both TECs and tumor cells derived from a seminoma exhibited increased C-X-C chemokine receptor type 7 (CXCR7) expression. However, CXCR7 expression was not detected in TECs and tumor cells derived from a hepatocellular carcinoma. Understanding TEC specific traits may be important in the development of more efficacious anti-angiogenic therapies that do not induce adverse effects.

著者

Akemi SUTO Yukinori SUTO Nozomi ONOHARA Yu TOMIZAWA Yukiko YAMAMOTO-SUGAWARA Taro OKAYAMA Kenichi MASUDA

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.14-0406, (Released:2014-10-29)

被引用文献数

5 17

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Canine atopic-like dermatitis (ALD) is suspected to be associated with food allergies, particularly those mediated by lymphocytes. In this study, 54 cases were included as ALD dogs, based on the negative IgE test results. In the dogs, the percentage of activated cells helper-T lymphocytes were measured by flow cytometry using cultured peripheral lymphocytes under food allergen stimulation. We observed that 49 of the 54 ALD dogs (90.7%) had positive lymphocyte reactions against one or more food allergens. The most common food allergen was soybean, showing positive results in 21 dogs (49.2%), while the allergen to cause the lowest number of reactions was catfish (only 5 dogs, 10.2%). These results may be useful in considering elimination diets for ALD dogs.

著者

Ya-Pei CHANG Hsuan-Ping HONG Yen-Hua LEE I-Hsuan LIU

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.14-0265, (Released:2014-11-12)

被引用文献数

2 8

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Mesenchymal stem cells (MSCs) hold great potential in cell therapy and have attracted increasing interests in a wide range of biomedical sciences. However, the scarcity of MSCs and the prolonged isolation procedure limited the clinical application. To address these two issues, we developed a method to isolate MSCs from bone biopsy tissues of euthanized canine body donors. Compared to the traditional method to isolate MSCs from aspirated bone marrow (BMSCs), the isolation procedure for MSCs from harvested epiphyseal cancellous bone (EMSCs) was less time-consuming. The isolated EMSCs had similar plastic-adherence, tri-lineage differentiation and consistent surface marker profiles compared to BMSCs. We harvested BMSCs and EMSCs from 24 euthanized cases from clinics and 42 euthanized donors from a local shelter. The successful rate for EMSC isolation is significantly higher compared to BMSC isolation, while the other properties of the isolated MSCs including the clonogenicity, proliferative potentials and molecular phenotypes were not discernibly different between the MSCs established by the two methods. In conclusion, we demonstrated a new procedure to harvest MSCs by bone biopsy at the epiphyseal region. This method is less time consuming and more reliable, and the resulting MSCs are comparable to those harvested by bone marrow aspiration. The combination of the two methods can greatly improve the efficiency to harvest MSCs.

著者

Rebecca C. REGAN Robert M. GOGAL Jr James P. BARBER R. Cary TUCKFIELD Elizabeth W. HOWERTH Jessica A. LAWRENCE

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.13-0537, (Released:2014-09-15)

被引用文献数

9

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Loperamide is a peripheral opiate agonist that can cause apoptosis and G2/M arrest in human cancer cell lines and may sensitize cells to chemotherapy. The objectives of this study were to investigate the effects of loperamide on viability, apoptosis and cell cycle kinetics in canine cancer cells and to establish whether the drug sensitizes cells to doxorubicin. Cell viability was assessed using Alamar Blue. Cell death and cell cycle were studied using flow cytometry with 7-Aminoactinomycin-D (7-AAD) and propidium iodide (PI), respectively. Loperamide decreased cell viability in a dose-dependent fashion and was most effective against canine osteosarcoma cells. In all cell lines, it induced a dose and time dependent apoptosis and resulted in accumulation in G0/G1. When co-incubated with doxorubicin, loperamide induced a synergistic cell kill in canine carcinoma cells. Investigation is warranted into the role of loperamide in the treatment of canine cancer.

著者

Özge TURNA YILMAZ TSF TOYDEMIR İ KIRŞAN B DOKUZEYLUL Z GUNAY E KARACAM

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.14-0112, (Released:2014-09-20)

被引用文献数

5

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The analgesic effect of wound infiltration with bupivacaine was evaluated in cats undergoing bilateral mastectomy. Twenty-one female cats with mammary gland tumors were anesthetized with propofol and oxygen-isoflurane anesthesia following premedication with atropine. In the trial group (Group I; n=11), 30 ml of saline containing 2 mg/kg of bupivacaine was infiltrated topically into the surgical wound right after removal of the mammary glands, whereas only saline solution was infiltrated in the control group (Group II; n=10). At the same time, carprofen (4 mg/kg) was also administered subcutaneously in both groups. Behavioral signs of pain were monitored during the recovery period after general anaesthesia. In order to examine the behavioral changes associated with acute pain, a questionnaire was prepared and given to the owners to be completed 4 hr and then 10 hr after the operation. According to the owners’ anwers to the questionnaire, a pain score was specified using a “numerical rating scale” for each cat. Although some cats showed mild to moderate pain, the pain score recorded at 4 hr after the operation was significantly lower in Group I (P<0.001). No significant difference was found at 10 hr after the operation between the groups. The incidence of vocalization, aggression and convulsion within 2 hr after the operation were also lower in Group I. In conclusion, wound infiltration with bupivacaine before incisional closure provided reliable analgesia at least 4 hr after bilateral radical mastectomy in cats.

著者

Kiwamu HANAZONO Shinya FUKUMOTO Yoshio KAWAMURA Yoshifumi ENDO Tsuyoshi KADOSAWA Hidetomo IWANO Tsuyoshi UCHIDE

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.14-0032, (Released:2014-09-16)

被引用文献数

2 27

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Transitional cell carcinoma (TCC), a urinary bladder tumor with high mortality, is encountered commonly in dogs. Whereas overexpression of epidermal growth factor receptor (EGFR) is associated with development of human urinary bladder cancer, information on EGFR expression in canine TCC is lacking. In this study, EGFR protein and mRNA expression in canine normal bladder (n=5), polypoid cystitis (n=5) and TCC (n=25) were examined by immunohistochemistry and real-time polymerase chain reaction. EGFR protein expression was significantly higher in TCC than that in normal healthy bladder (P<0.001) and polypoid cystitis (P<0.005). High EGFR protein expression was significantly (P<0.01) associated with TCC with a sensitivity of 72% and specificity of 100%. Comparative analysis of protein and mRNA expression levels in TCC showed significant positive correlation (r=0.88, P<0.05) between mRNA and protein expression. These findings suggest that intense expression of EGFR protein could be used as a marker to help canine TCC diagnosis.

著者

Dah-Renn FU Daiki KATO Ai WATABE Yoshifumi ENDO Tsuyoshi KADOSAWA

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.14-0245, (Released:2014-08-25)

被引用文献数

2 10

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Apoptosis, Ki-67 and survivin expression have been reported as prognostic values in human cancer treated with radiation therapy. The aim of this study was to evaluate the correlation between the outcome of canine nasal carcinomas treated with radiation therapy and these cancer markers. The apoptotic index (AI) was evaluated with TUNEL assays, and an immunohistochemical evaluation was performed on Ki-67 and survivin in 33 biopsy samples taken before treatment. Median survival times were estimated using Kaplan-Meier curves and the log-rank method. The AI ranged from 0 to 0.7%, and the percentage of Ki-67-positive cells defined as the proliferative index (PI) ranged from 0.8 to 77% in all samples. Neither the AI nor the PI had a significant relationship with survival time (P=0.056 and 0.211). Survivin expression was detected in 84.9% of samples of canine nasal carcinoma. Dogs with high survivin expression were associated with poorer response to treatment and had shorter survival times (P=0.017 and 0.031). Advanced-stage tumors were also significantly associated with a high level of survivin (P=0.026). Overexpression of survivin was shown to be an unfavorable prognostic factor in dogs with nasal carcinomas treated with radiation therapy.

著者

Supannika HANTRAKUL Narumol KLANGKAEW Sunee KUNAKORNSAWAT Tawewan TANSATIT Ammart POAPOLATHEP Susumu KUMAGAI Saranya POAPOLATHEP

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.14-0180, (Released:2014-08-21)

被引用文献数

16

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This study was conducted to evaluate the pharmacokinetic characteristics of vincristine and their correlation with its clinical effects in dogs with transmissible venereal tumor (TVT). Dogs with TVT were intravenously administered vincristine sulfate at a dose of 0.7 mg/m2 of body surface area. Blood samples were collected starting from 5 min to 48 hr after drug administration. The plasma concentration of vincristine was determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The pharmacokinetic parameters of vincristine were characterized using a two-compartmental pharmacokinetic model. The volume of distribution, distribution half-life, elimination half-life, and plasma clearance were 0.660 ± 0.210 l/kg, 21.5 ± 6.90 min, 47.6 ± 14.2 min, and 0.010 ± 0.001 l/min/kg, respectively. Tumor regression was determined at weekly interval by a physical examination and histopathological analysis. In our study, three to eight administrations of vincristine at a dose of 0.7 mg/m2 were able to induce a complete tumor regression without any evidence of gross lesion of disease. Therefore, this investigation provides the pharmacokinetic characteristics of vincristine in dogs with TVT, which may be used as an integration tool to gain a better understanding of the disposition properties of the drug and the correlation of these properties with the drug’s clinical effects. In addition, we validated the LC-MS/MS method and found that it is suitable for the pharmacokinetic study of vincristine in dog plasma.

著者

Reo TAMAI Masaru FURUYA Shingo HATOYA Hideo AKIYOSHI Ryohei YAMAMOTO Yoshiaki KOMORI Shin-ichi YOKOI Kenichiro TANI Yuji HIRANO Masayuki KOMORI Shigeo TAKENAKA

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.14-0043, (Released:2014-08-13)

被引用文献数

3 14

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Canine lymphoma is a common cancer that has high rates of complete remission with combination chemotherapy. However, the duration of remission varies based on multiple factors, and there is a need to develop a method for early detection of recurrence. In this study, we compared the metabolites profiles in serum from 21 dogs with lymphoma and 13 healthy dogs using gas chromatography mass spectrometry (GC-MS). The lymphoma group was separated from the control group in an orthogonal projection to latent structure with discriminant analysis (OPLS-DA) plot using ions of m/z 100–600, indicating that the metabolites profiles in lymphoma cases differed from those in healthy dogs. The lymphoma group was also separated from the control group on OPLS-DA plot using 29 metabolites identified in all serum samples. Significant differences were found for 16 of these metabolites with higher levels in the lymphoma group for 15 of the metabolites and lower levels for inositol. An OPLS-DA plot showed separation of the lymphoma and healthy groups using these 16 metabolites only. These results indicate that metabolites profile with GC-MS may be a useful tool for detection of potential biomarker and diagnosis of canine lymphoma.

著者

Kota YOSHIDA Saori YOSHIDA Nan CHOISUNIRACHON Tomochika SAITO Kaori MATSUMOTO Kohei SAEKI Manabu MOCHIZUKI Ryohei NISHIMURA Nobuo SASAKI Takayuki NAKAGAWA

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.14-0104, (Released:2014-06-16)

被引用文献数

3 14

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It is known that epithelial mesenchymal transition (EMT) contributes to the acquisition of malignant property in human cancers. However, the role of EMT in canine tumors remains to be elucidated. To evaluate the correlation between expression levels of protein markers involved in EMT and clinicopathological characteristics in canine mammary gland tumors, immunohistochemistry using antibodies against ZO-1, E-cadherin, vimentin, N-cadherin and fibronectin was performed on 119 clinical tissue samples. Consequently, loss of ZO-1 and E-cadherin, and gain of vimentin and N-cadherin were more frequently observed in malignant tumors than in benign tumors. However, there was no correlation among expression of these molecules. Univariate and multivariate analysis identified that loss of E-cadherin independently had a low one-year survival rate (adjusted odds ratio: 2.3, P=0.02). These results suggested that EMT might relate to acquisition of malignancy, and additionally, E-cadherin was strongly correlated with malignant behavior in canine mammary gland tumors.

著者

Takashi TAMAMOTO Koichi OHNO Yuko GOTO-KOSHINO Hajime TSUJIMOTO

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.14-0108, (Released:2014-05-15)

被引用文献数

1 9

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The serum amyloid A (SAA) concentration is higher in mammary tumors with metastases in both humans and animals. In the present study, the direct effects of recombinant feline SAA (rfSAA) protein on invasiveness of feline mammary carcinoma cells were evaluated. As an indicator of invasiveness, matrix metalloproteinase-9 (MMP-9) expression was investigated in 4 feline mammary carcinoma cell lines of different origins. In 3 of 4 cell lines, MMP-9 expression was significantly increased by rfSAA stimulation. The invasive capacities of feline mammary carcinoma cells were also stimulated by rfSAA. The findings of this study have identified a novel role for SAA in mammary tumorigenesis and suggest that therapeutic strategies targeting SAA may provide new alternatives in treating tumor invasion and metastasis.

著者

Masashi TAKAHASHI Yuko GOTO-KOSHINO Kenjiro FUKUSHIMA Hideyuki KANEMOTO Ko NAKASHIMA Yasuhito FUJINO Koichi OHNO Yasuyuki ENDO Hajime TSUJIMOTO

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.13-0345, (Released:2014-02-10)

被引用文献数

10

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Nimustine (ACNU) is an alkylating agent of the nitrosourea and can be an antineoplastic agent in dogs. But, there has been no report on its dose-limiting toxicity (DLT) in dogs. This study was a phase I dose-escalation clinical trial to determine the maximum tolerated dose (MTD) and DLT of ACNU in tumor-bearing dogs. The starting dosage was 25 mg/m2, and subsequent dosages were administered in increments of 5 mg/m2 in cohort of 3 dogs. Eight dogs were included and the MTD was determined to be 25 mg/m2, DLT was neutropenia and the optimal interval was considered to be 21 days. The data herein provides a basis for the subsequent phase II trial of ACNU in dogs.

著者

Yuko NAKANO Tetsuya KOBAYASHI Fukiko OSHIMA Eri FUKAZAWA Tetsushi YAMAGAMI Yozo SHIRAISHI Masamine TAKANOSU

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.13-0156, (Released:2013-11-29)

被引用文献数

4 12

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In 2 individual cases of canine mast cell tumors, we identified 2 novel c-KIT mutations in exon 11: a 9-base pair (bp) deletion (c.1663-1671del) and a point mutation (c.1676T>A). The 9-bp deletion mutation caused a loss of 3 amino acids, corresponding to p.Gln555_Lys557del, and the point mutation resulted in the substitution of valine by aspartic acid (p.Val559Asp) in the juxtamembrane domain of the protein. Imatinib mesylate, a therapeutic agent for canine mast cell tumors, was used to treat both tumors. Complete remission was achieved at 33 and 14 days after administration, respectively. However, in both cases, the therapeutic response subsequently tapered with the duration of remission lasting 66 and 255 days, respectively. Although these 2 novel c-KIT mutations in exon11 were not confirmed to be gain-of-function mutations, a further study may help clarify relevance between mutations identified in this report and responsiveness.

著者

Atsuki IJIRI Ken YOSHIKI Shizuka TSUBOI Hitsoshi SHIMAZAKI Hideo AKIYOSHI Tetsuya NAKADE

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.12-0373, (Released:2013-11-08)

被引用文献数

18

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To report the effectiveness of MRI scanning during brain meningioma resection surgery in canine and feline. Twenty three cases from 2006 to 2008 in canine and feline diagnosed with meningioma. All were aged between 8 years and 16 years old. There were 12 males and 11 females. Appropriate craniotomy was performed for each case according to the initial MRI taken to diagnose meningioma prior to the surgery. Once dura mater was exposed, an MRI biopsy needle was placed in the tumor as a guide. 1st MRI during the surgery was scanned with this needle to confirm the location of the tumor. This MRI image was also processed and displayed by MPR to reveal the tumor extent in three dimensions. Sonopet was applied in the middle of the tumor to destroy the inner part and release pressure from the entire tumor. Creating some space between the brain tissue and tumor, we treated blood vessels and carefully resected them. This procedure was repeated until complete removal of the tumor was confirmed by MRI. Sixteen of the twenty three cases survived for more than 2 years postoperatively. The other seven died due to other disorders within 2 years. Our method with MRI navigation during the surgery improved our surgical performance and contributed to a prolonged survival time for the patients. In order to perform multiple MRI procedures smoothly during the surgery, it is necessary to have skillful assistants.

著者

Gentoku IIDA Kazushi ASANO Mamiko SEKI Manabu SAKAI Kenji KUTARA Kumiko ISHIGAKI Yumiko KAGAWA Orie YOSHIDA Kenji TESHIMA Kazuya EDAMURA Toshihiro WATARI

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.13-0378, (Released:2013-11-01)

被引用文献数

4

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The purpose of this study was to evaluate the gene expression of growth factors and growth factor receptors of primary hepatic masses, including hepatocellular carcinoma (HCC) and nodular hyperplasia (NH), in dogs. Quantitative real-time reverse transcriptase-polymerase chain reaction was performed to measure the expression of 18 genes in 18 HCCs, 10 NHs, 11 surrounding non-cancerous liver tissues and 4 healthy control liver tissues. Platelet-derived growth factor-B (PDGF-B), transforming growth factor-α, epidermal growth factor receptor, epidermal growth factor and hepatocyte growth factor were found to be differentially expressed in HCC compared with NH and the surrounding non-cancerous and healthy control liver tissues. PDGF-B is suggested to have the potential to become a valuable ancillary target for the treatment of canine HCC.

著者

Hirotaka TOMIYASU Yuko GOTO-KOSHINO Yasuhito FUJINO Koichi OHNO Hajime TSUJIMOTO

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.13-0337, (Released:2013-10-25)

被引用文献数

4 5

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Treatments for canine lymphoma often fail because tumor cells acquire multidrug resistance (MDR). MDR can develop through several mechanisms, among which the overexpression of drug transporters in tumor cells is a well-studied mechanism. ATP-binding cassette sub-family G member 2 (ABCG2) belongs to the ABC-transporters, that are representative drug efflux pumps associated with MDR in human tumor cells. However, the regulation of ABCG2 gene expression in canine tumors is not well understood. The purpose of the present study was to reveal the regulatory mechanism of ABCG2 gene expression in 4 canine lymphoid tumor cell lines, GL-1, CLBL-1, UL-1 and Ema. Treatment with phorbol 12-myristate 13-acetate (PMA), the protein kinase C (PKC) activator, stimulated MAPK/ERK pathway in GL-1, UL-1 and Ema cells and JNK pathway in UL-1 and Ema cells. When GL-1 and UL-1 cells were treated with PMA and the MAPK/ERK kinase inhibitor U0126, ABCG2 gene expression levels were elevated above those in untreated cells. Similarly, ABCG2 gene expression increased above control levels in UL-1 and Ema cells treated with PMA and the JNK inhibitor SP600125. However, ABCG2 gene expression was unaffected by U0126 exposure in CLBL-1 cells, in which activation of MAPK/ERK pathway was observed in non-treated cells. These results suggested that MAPK/ERK and JNK pathways downregulate ABCG2 gene expression, which is upregulated by unidentified but possibly PKC-dependent pathways, in several types of canine lymphoid tumor cells.

著者

Seishiro CHIKAZAWA Yasunori KITAHARA Erika ANDO Yasutomo HORI Fumio HOSHI Kazutaka KANAI Naoyuki ITO Seiichi HIGUCHI

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.13-0319, (Released:2013-09-20)

被引用文献数

1 2

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Antimalarial drugs, dihydroartemisinin (DHA) and artesunate (ATS), exhibit iron-dependent cytotoxicity in tumor cells. We hypothesized that erythrophagocytic uptake of heme-iron enhances the cytotoxicity of DHA and ATS. Erythrophagocytic (EP) treatment of the canine histiocytic sarcoma cell line DH82 markedly increased the cytotoxicity of DHA and ATS compared to controls. Succinyl acetone, an inhibitor of intracellular heme synthesis, decreased the cytotoxicity of DHA and ATS in normal cells, but this change was not observed in EP cells. These results suggest that exogenous heme derived from erythrocytes can enhance the cytotoxicity of DHA and ATS. Furthermore, our study suggests that heme could be a novel component of tumor treatment in veterinary medicine.