C-kit as a prognostic and therapeutic marker in canine cutaneous mast cell tumours: From laboratory to clinic

Costa, Rui M. Gil da

doi:10.1016/j.tvjl.2015.05.002

Cited by 22 publications

(13 citation statements)

References 72 publications

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“…In canines, cutaneous mast cell tumor (MCT) is the most common skin tumor, and KIT mutations cause a constitutive protein activation, resulting in uncontrolled mast cell proliferation (Gil da Costa, 2015). The advent of targeted therapy and particularly the use of tyrosine kinase inhibitors (TKIs) brought some therapeutic benefits to the approach to MCTs; however, the potential for drug-resistance phenomena and the need to choose the best anticancer drug according to KIT mutational profile represent common problems (London et al, 2009;Bonkobara, 2015).…”

Section: Introductionmentioning

confidence: 99%

Targeting CanineKITPromoter by Candidate DNA G-Quadruplex Ligands

Zorzan

Ros

Giantin

et al. 2018

J Pharmacol Exp Ther

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G-quadruplexes (G4) are nucleic acid secondary structures frequently assumed by G-rich sequences located mostly at telomeres and proto-oncogenes promoters. Recently, we identified, in canine KIT (v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog) promoter, two G-rich sequences able to fold into G4: d_kit1 and d_kit2_A16. In this study, an anthraquinone (AQ1) and an anthracene derivative (AN6), known to stabilize the G4 structures of the corresponding human h_kit1 and h_kit2, were tested on the canine G4 and in two canine mast cell tumor (MCT) cell lines (C2 and NI-1) to verify their capability to down-regulate KIT expression. The cytotoxicity of AQ1 and AN6 was determined using the Alamar Blue test; also the constitutive expression of KIT and other proto-oncogenes containing G4 structures in their promoter (BCL2, VEGFa, VEGFR2, KRAS, and TERT) was assessed by quantitative real-time polymerase chain reaction (qRT-PCR). Then the time-and dose-dependent effects of both ligands on target gene expression were assessed by qRT-PCR. All target genes were constitutively expressed up to 96 hours of culture. Both ligands decreased KIT mRNA levels and c-kit protein amount, and AN6 was comparatively fairly more effective. DNA interaction studies and a dualluciferase gene reporter assay performed on a noncancerous canine cell line (Madin-Darby Canine Kidney cells) proved that this down-regulation was the result of the interaction of AN6 with KIT proximal promoter. Interestingly, our results only partially overlap with those previously obtained in human cell lines, where AQ1 was found as the most effective compound. These preliminary data might suggest AN6 as a promising candidate for the selective targeting of canine KIT-dependent tumors.

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Section: Introductionmentioning

confidence: 99%

Targeting CanineKITPromoter by Candidate DNA G-Quadruplex Ligands

Zorzan

Ros

Giantin

et al. 2018

J Pharmacol Exp Ther

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“…Over recent years, abnormalities of tyrosine kinase function, such as mutations or overexpression, have been demonstrated in many human and veterinary cancers (London 2004 -review). In canine MCTs, mutations in the c-kit gene affect 30 to 40% of tumours, with a higher prevalence in higher grade tumours (Webster et al 2006, Gil da Costa 2015.…”

Section: Example 2: Canine Mctsmentioning

confidence: 99%

“…In canine MCTs, mutations in the c‐kit gene affect 30 to 40% of tumours, with a higher prevalence in higher grade tumours (Webster et al . , Gil da Costa ).…”

Section: Introductionmentioning

confidence: 99%

Significant advances in veterinary oncology – 60 years on

Dobson

2019

J of Small Animal Practice

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The first edition of the Journal of Small Animal Practice published in February 1960, contained a paper entitled “Recent Treatments of Malignant Neoplasia” by Dr Larry Owen. Now we have reached the 60th anniversary of JSAP, that article provides a baseline from which to review subsequent advances in veterinary oncology, which now includes worldwide networks that have resulted in veterinary oncology becoming the multidisciplinary speciality that it is today. There certainly have been many advances in understanding of the pathology and epidemiology of animal cancers and in methods of diagnosis and treatment. However, the subject has become so large and diverse that not all aspects can be covered in detail here. It should also be acknowledged that there are still many gaps in knowledge in this field and that, because of a lack of randomised clinical trials, the evidence base for what is often regarded as “standard of care” is weak.

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“…Finally, a connection was found between c-KIT gene mutations, elevated c-KIT mRNA expression and a higher grade of tumor ( 15 , 23 – 27 ). Consequently, c-KIT mutations in tumor tissues are related to shorter survival times ( 28 , 29 ). These mutations are present in 50% of high grade and in 9–15% of overall MCT cases ( 28 – 30 ).…”

Section: Introductionmentioning

confidence: 99%

“…Consequently, c-KIT mutations in tumor tissues are related to shorter survival times ( 28 , 29 ). These mutations are present in 50% of high grade and in 9–15% of overall MCT cases ( 28 – 30 ).…”

Section: Introductionmentioning

confidence: 99%

Oncolytic Sendai Virus Therapy of Canine Mast Cell Tumors (A Pilot Study)

et al. 2018

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Background: Canine mastocytomas (mast cell tumors) represent a common malignancy among many dog breeds. A typical treatment strategy for canine mastocytomas includes surgery, chemo- and radio-therapy, although in many cases the therapy fails and the disease progression resumes. New treatment approaches are needed.Aims: The goal of this pilot study was to examine safety and efficacy of oncolytic Sendai virus therapy administered to canine patients with cutaneous or subcutaneous mastocytomas.Materials and Methods: Six canine patients, with variable grades and stages of the disease, received virus therapy, either as a monotherapy, or in combination with surgery. The therapy included two or more virus applications administered weekly or biweekly. Each application of Sendai virus (107-108.6 EID50) consisted of multiple individual 0.01–0.1 ml injections delivered intratumorally, intradermally around a tumor, and under a tumor bed.Results: The treatment was well tolerated, with minor transitory side effects. Of the six dogs, two did not receive surgery or any other treatment besides the virus injections. The other four animals underwent radical or debulking surgeries, and in three of them the subsequent administration of Sendai virus completely cleared locally recurrent or/and remaining tumor masses. Five dogs demonstrated a complete response to the treatment, the animals remained disease free during the time of observation (2–3 years). One dog responded only partially to the virotherapy; its after-surgical recurrent tumor and some, but not all, metastases were cleared. This dog had the most advanced stage of the disease with multiple enlarged lymph nodes and cutaneous metastases.Conclusion: The results of the pilot study suggest that Sendai virus injections could be safe and efficient for the treatment of dogs affected by mastocytomas.They also suggest the need of further studies for finding optimal schemes and schedules for this kind of therapy.

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C-kit as a prognostic and therapeutic marker in canine cutaneous mast cell tumours: From laboratory to clinic

Cited by 22 publications

References 72 publications

Targeting CanineKITPromoter by Candidate DNA G-Quadruplex Ligands

Targeting CanineKITPromoter by Candidate DNA G-Quadruplex Ligands

Significant advances in veterinary oncology – 60 years on

Oncolytic Sendai Virus Therapy of Canine Mast Cell Tumors (A Pilot Study)

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