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1.
C. C. Hwang M. Igase M. Sakurai T. Haraguchi K. Tani K. Itamoto T. Shimokawa M. Nakaichi Y. Nemoto S. Noguchi M. Coffey M. Okuda T. Mizuno 《Veterinary and comparative oncology》2018,16(2):229-238
Oncolytic virotherapy is a novel treatment involving replication‐competent virus in the elimination of cancer. We have previously reported the oncolytic effects of reovirus in various canine cancer cell lines. This study aims to establish the safety profile of reovirus in dogs with spontaneously occurring tumours and to determine a recommended dosing regimen. Nineteen dogs with various tumours, mostly of advanced stages, were treated with reovirus, ranging from 1.0 × 108 to 5.0 × 109 TCID50 given as intratumour injection (IT) or intravenous infusion (IV) daily for up to 5 consecutive days in 1 or multiple treatment cycles. Adverse events (AEs) were graded according to the Veterinary Cooperative Oncology Group‐ Common Terminology Criteria for Adverse Events (VCOG‐CTCAE) v1.1 guidelines. Viral shedding, neutralizing anti‐reovirus antibody (NARA) production and immunohistochemical (IHC) detection of reovirus protein in the tumours were also assessed. AE was not observed in most dogs and events were limited to Grade I or II fever, vomiting, diarrhoea and inflammation of the injected tumour. No infectious virus was shed and all dogs had elevated NARA levels post‐treatment. Although IHC results were only available in 6 dogs, 4 were detected positive for reovirus protein. In conclusion, reovirus is well‐tolerated and can be given safely to tumour‐bearing dogs according to the dosing regimen used in this study without significant concerns of viral shedding. Reovirus is also potentially effective in various types of canine tumours. 相似文献
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Masaya Igase Kazuha Shousu Noriyuki Fujiki Masashi Sakurai Makoto Bonkobara Chung C. Hwang Matt Coffey Shunsuke Noguchi Yuki Nemoto Takuya Mizuno 《Veterinary and comparative oncology》2019,17(2):184-193
Canine histiocytic sarcoma is an aggressive, fatal neoplastic disease with a poor prognosis. Lomustine is generally accepted as the first‐line systemic therapy, although this compound does not provide complete regression. Therefore, research into a novel approach against canine histiocytic sarcoma is needed. However, anti‐tumour effects of oncolytic therapy using reovirus against histiocytic sarcoma are unknown. Here, we showed that reovirus has oncolytic activity in canine histiocytic sarcoma cell lines in vitro and in vivo. We found that reovirus can replicate and induce caspase‐dependent apoptosis in canine histiocytic sarcoma cell lines. A single intra‐tumoural injection of reovirus completely suppressed the growth of subcutaneously grafted tumours in NOD/SCID mice. Additionally, we demonstrated that susceptibility to reovirus‐induced cell death was attributable to the extent of expression of type I interferons induced by reovirus infection in vitro. In conclusion, oncolytic reovirus appears to be an effective treatment option for histiocytic sarcoma, and therefore warrants further investigation in early clinical trials. 相似文献
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Anti‐tumour activity of oncolytic Western Reserve vaccinia viruses in canine tumour cell lines,xenografts, and fresh tumour biopsies 下载免费PDF全文
K. Autio A. Knuuttila M. Ahonen S. Parviainen A. Kanerva T. Hakonen A. Hemminki 《Veterinary and comparative oncology》2016,14(4):395-408
Cancer is one of the most common reasons for death in dogs. One promising approach is oncolytic virotherapy. We assessed the oncolytic effect of genetically modified vaccinia viruses in canine cancer cells, in freshly excised tumour biopsies, and in mice harbouring canine tumour xenografts. Tumour transduction efficacy was assessed using virus expressing luciferase or fluorescent marker genes and oncolysis was quantified by a colorimetric cell viability assay. Oncolytic efficacy in vivo was evaluated in a nude mouse xenograft model. Vaccinia virus was shown to infect most tested canine cancer cell lines and primary surgical tumour tissues. Virus infection significantly reduced tumour growth in the xenograft model. Oncolytic vaccinia virus has antitumour effects against canine cancer cells and experimental tumours and is able to replicate in freshly excised patient tumour tissue. Our results suggest that oncolytic vaccinia virus may offer an effective treatment option for otherwise incurable canine tumours. 相似文献
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Yusuke IZUMI Yuki HOSHINO Kenji HOSOYA Satoshi TAKAGI Masahiro OKUMURA 《The Journal of veterinary medical science / the Japanese Society of Veterinary Science》2015,77(3):359-363
The present study involved the isolation and characterization of canine tumor endothelial
cells (TECs) from 2 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. 相似文献
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Kiwamu HANAZONO Shinya FUKUMOTO Yoshio KAWAMURA Yoshifumi ENDO Tsuyoshi KADOSAWA Hidetomo IWANO Tsuyoshi UCHIDE 《The Journal of veterinary medical science / the Japanese Society of Veterinary Science》2015,77(1):1-6
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. 相似文献
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Kosei SAKAI Tomohiro YONEZAWA Hideyuki YAMAWAKI Toshifumi OYAMADA 《The Journal of veterinary medical science / the Japanese Society of Veterinary Science》2015,77(10):1319-1322
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. 相似文献
7.
Amy L. MacNeill 《Veterinary and comparative oncology》2020,18(1):36-42
Replicating oncolytic viruses (OVs) are appealing, new, FDA‐approved, therapeutic options for humans with head and neck cancers and melanomas. These treatments are not yet available for veterinary patients, but recent clinical trials have shown several OVs to be safe in dogs and cats. Specific viruses being used to treat sarcomas in dogs include modified canine adenovirus 2, myxoma virus, vesicular stomatitis virus and reovirus. In cats with vaccine‐associated sarcomas, poxviruses have been injected postoperatively and a reduced rate of tumour recurrence was documented. To date, the response rates of canine and feline patients to OV therapy have been variable (as they are in people). Optimal methods of OV administration and dosing schedules continue to be evaluated. One way to improve outcomes of OV therapy in veterinary patients may be to use OVs in combination with other immunomodulatory therapies. This review discusses the potential utility of concurrent therapy with an OV and an inhibitor of the type I interferon pathway. 相似文献
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Despite advances in conventional therapeutics, cancer remains an invariably fatal disease, the major challenge being to develop tumour‐specific cancer treatment strategies. Current treatments such as chemotherapy and radiotherapy rely on a crude distinction between cancer cells and normal cells. However, with an increased understanding of the molecular events in the development of cancer, it is possible that far more innovative and targeted approaches can be developed. From studies on humans and dogs, the enzyme telomerase has emerged as a central unifying mechanism underlying the immortal phenotype of cancer and has thus become a candidate for differentiating between normal and cancer cells. The level and frequency of telomerase activity and component gene expression in cancers reinforces this as a potential target for cancer therapies. This article describes two approaches to target cancer by capitalizing on the expression of this enzyme. In the first approach, we target the enzyme itself, the goal being to cause cancer cell death. In the second approach, we utilize the respective gene promoters for telomerase component enzymes to drive expression of a reporter gene in cancer cell lines. The results demonstrated that targeted gene expression using promoter elements can be achieved specifically in telomerase‐positive cell lines. However, targeting the enzyme itself proved less successful and warrants investigations into alternative approaches. 相似文献
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Ayano KUDO Sho YOSHIMOTO Hiromitsu YOSHIDA Yusuke IZUMI Satoshi TAKAGI 《The Journal of veterinary medical science / the Japanese Society of Veterinary Science》2022,84(6):784
Cancer-associated fibroblasts (CAFs) play an essential role in tumor invasion and metastasis. In dogs, the biological features of CAFs have not been well characterized. The purpose of this study was to investigate differences in the biological activities of canine CAFs and normal fibroblasts (NFs), and their influence on the migration and invasion of cancer cells. Canine CAFs and NFs were harvested from surgically-resected malignant epithelial tumor tissues and skin tissues of dogs. A wound-healing assay was conducted to compare the migratory and invasive abilities of canine CAFs and NFs. The results of this study showed that canine CAFs have a greater migratory and invasive ability than NFs. To observe the indirect and direct interactions between fibroblasts and cancer cells, Boyden chamber assay and 3D co-culture with collagen gel were conducted. The number of migrated and infiltrated cancer cells co-cultured with canine CAFs was greater than that with NFs. In the 3D co-culture, cancer cells showed noteworthy proliferation on the surface of gels containing canine CAFs and invasion into the gel. On the other hand, no infiltration of cancer cells into the gel containing NFs was observed. It was suggested that canine CAFs activate migration and invasion of cancer cells and promote the infiltration of cancer cells into collagen gels. 相似文献
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A. Carlson K. S. Alderete M. K. O. Grant D. M. Seelig L. C. Sharkey B. N. M. Zordoky 《Veterinary and comparative oncology》2018,16(2):253-261
Hemangiosarcoma (HSA) is a highly malignant tumour with aggressive biological behaviour. HSAs are more common in dogs than other domestic animals. The median survival time of dogs with HSA remains short, even with chemotherapy and surgery. Therefore, there is a critical need to improve the adjuvant chemotherapeutic regimens to improve clinical outcomes in dogs with HSA. Resveratrol has been shown to possess strong anti‐proliferative and/or pro‐apoptotic properties in human cancer cell lines. Nevertheless, the potential anticancer effects of resveratrol have not been reported in canine HSAs. The objective of this study is to determine the growth inhibitory effects of resveratrol in HSA cells when used alone or in combination with doxorubicin, a commonly used chemotherapeutic agent. Frog and DD‐1 canine HSA cell lines were treated with varying concentrations of resveratrol with and without doxorubicin. Cell viability was measured by the MTT assay. The expression of apoptotic proteins, activation of p38 mitogen‐activated protein kinase (MAPK), AMP‐activated protein kinase (AMPK) and extracellular signal‐regulated kinase 1/2 (ERK1/2) were assessed by western blotting. Similar to human cancer cell lines, resveratrol markedly inhibited the growth and induced apoptosis in both HSA cell lines. Mechanistically, resveratrol activated p38 MAPK, but did not affect the AMPK or the ERK1/2 pathways. Additional experiments showed that resveratrol augmented the growth‐inhibitory and apoptotic effects of doxorubicin in both HSA cell lines. These findings suggest that resveratrol has pro‐apoptotic effects in canine HSA cells; therefore, its use as a potential adjunct therapy in canine HSA patients warrants further investigation. 相似文献
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Satoshi MATSUYAMA Yuko NAKANO Mieko NAKAMURA Ryohei YAMAMOTO Terumasa SHIMADA Fumihito OHASHI Kihei KUBO 《The Journal of veterinary medical science / the Japanese Society of Veterinary Science》2015,77(1):101-104
Prohibitin is an antiproliferative protein that is a product of a putative tumor
suppressor gene. However, there is little information on prohibitins in companion animals.
In this study, we cloned canine prohibitin mRNA using RT-PCR and 3′-RACE (Rapid
Amplification of cDNA Ends). The sequence was well conserved compared with those of other
mammals, including human. The deduced amino acid sequence translated from the open reading
frame completely corresponded to the human sequence. Canine prohibitin mRNA was expressed
in all normal mammary and tumor samples examined. These results suggest that this protein
plays a vital role in cell growth mechanisms and may be related to the occurrence of
canine mammary tumors. 相似文献
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Morgan S. Schrock Abigail A. Zalenski Miranda M. Tallman Luke Kollin Anna Bratasz Griffin Weeks Margaret A. Miller Courtney N. Sweeney G. Elizabeth Pluhar Michael R. Olin William C. Kisseberth R. Timothy Bentley Peter J. Dickinson Daniel York Amy Webb Xu Wang Sarah Moore Monica Venere Matthew K. Summers 《Veterinary and comparative oncology》2023,21(3):492-502
High-grade glioma is an aggressive cancer that occurs naturally in pet dogs. Canine high-grade glioma (cHGG) is treated with radiation, chemotherapy or surgery, but has no curative treatment. Within the past eight years, there have been advances in our imaging and histopathology standards as well as genetic charactereization of cHGG. However, there are only three cHGG cell lines publicly available, all of which were derived from astrocytoma and established using methods involving expansion of tumour cells in vitro on plastic dishes. In order to provide more clinically relevant cell lines for studying cHGG in vitro, the goal of this study was to establish cHGG patient-derived lines, whereby cancer cells are expanded in vivo by injecting cells into immunocompromized laboratory mice. The cells are then harvested from mice and used for in vitro studies. This method is the standard in the human field and has been shown to minimize the acquisition of genetic alterations and gene expression changes from the original tumour. Through a multi-institutional collaboration, we describe our methods for establishing two novel cHGG patient-derived lines, Boo-HA and Mo-HO, from a high-grade astrocytoma and a high-grade oligodendroglioma, respectively. We compare our novel lines to G06-A, J3T-Bg, and SDT-3G (traditional cHGG cell lines) in terms of proliferation and sensitivity to radiation. We also perform whole genome sequencing and identify an NF1 truncating mutation in Mo-HO. We report the characterization and availability of these novel patient-derived lines for use by the veterinary community. 相似文献
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K. A. Wirth K. Kow M. E. Salute N. J. Bacon R. J. Milner 《Veterinary and comparative oncology》2016,14(3):281-294
Yunnan Baiyao is a Chinese herbal medicine that has been utilized for its anti‐inflammatory, haemostatic, wound healing and pain relieving properties in people. It has been utilized in the veterinary profession to control bleeding in dogs with hemangiosarcoma (HSA) and has been anecdotally reported to prolong survival times in dogs with this neoplasm. This study evaluated the in vitro activity of Yunnan Baiyao against three canine HSA cell lines after treatment with increasing concentrations of Yunnan Baiyao (50, 100, 200, 400, 600 and 800 µg mL?1) at 24, 48 and 72 h. Mean half maximum inhibitory concentration (IC50) at 72 h for DEN, Fitz, SB was 369.9, 275.9 and 325.3 µg mL?1, respectively. Caspase‐3/7 activity increased in correlation with the IC50 in each cell line which was confirmed by the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL, APO‐BRDU Kit; BD Biosciences, San Jose, CA, USA) assay. VEGF in cell supernatant was also quantified. Overall, the study found that Yunnan Baiyao causes dose and time dependent HSA cell death through initiation of caspase‐mediated apoptosis, which supports future studies involving Yunnan Baiyao. 相似文献
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Margherita Orlandi Maurizio Mazzei Marta Vascellari Erica Melchiotti Claudia Zanardello Ranieri Verin Francesco Albanese Fabiano Necci Luca Pazzini Giulia Lazzarini Francesca Abramo 《Journal of veterinary diagnostic investigation》2021,33(6):1069
Numerous canine papillomaviruses (CPVs) have been identified (CPV1–23). CPV1, 2, and 6 have been associated with inverted papillomas (IPs). We retrieved 19 IPs from 3 histopathology archives, and evaluated and scored koilocytes, inclusion bodies, giant keratohyalin granules, cytoplasmic pallor, ballooning degeneration, and parakeratosis. IHC targeting major capsid proteins of PV was performed, and CPV genotyping was achieved by PCR testing. Tissue localization of CPV DNA and RNA was studied by chromogenic and RNAscope in situ hybridization (DNA-CISH, RNA-ISH, respectively). IPs were localized to the limbs (50%), trunk (30%), and head (20%), mainly as single nodules (16 of 19). In 15 of 19 cases, immunopositivity was detected within the nuclei in corneal and subcorneal epidermal layers. PCR revealed CPV1 in 11 IPs and CPV2 DNA in 3 IPs. Overall, 14 of 17 cases were positive by both DNA-CISH and RNA-ISH, in accord with PCR results. A histologic score >5 was always obtained in cases in which the viral etiology was demonstrated by IHC, DNA-CISH, and RNA-ISH. IHC and molecular approaches were useful to ascertain the viral etiology of IPs. Although IHC is the first choice for diagnostic purposes, ISH testing allows identification of PV type and the infection phase. RNA-ISH seems a promising tool to deepen our understanding of the pathogenesis of different PV types in animal species. 相似文献
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Kikumi OGIHARA Yuko NAYA Reiichiro SATO Ken ONDA Hideharu OCHIAI 《The Journal of veterinary medical science / the Japanese Society of Veterinary Science》2015,77(5):527-534
Analysis of L-type amino acid transport expression of hepatocellular carcinoma cells
(HCCs) of the dog was performed. The leucine transport activity of canine HCCs was 0.628 ±
0.018 nmol/mg protein/min. The inhibitor of LAT 2-aminobicyclo[2.2.1]heptane-2-carboxylic
acid (BCH) reduced 90% of the activity at 1 mM. The deduced amino acid sequences of canine
LAT2, LAT3 and LAT4 were well conserved in mammalians, exhibiting 89, 88 and 77% homology,
respectively. RT-PCR revealed distinct LAT1 expression compared with normal hepatocytes.
Western blotting analysis confirmed the potent LAT1 expression in canine HCCs but not
hepatocytes, and real-time RT-PCR analysis indicated that canine HCCs possessed 28 times
higher LAT1 expression than hepatocytes. These results indicated that the leucine
transport activity of canine HCCs was due to LAT1. 相似文献