Effects of gemcitabine and gemcitabine in combination with carboplatin on five canine transitional cell carcinoma cell lines

Galvao, Joao Felipe de Brito; Kisseberth, William C.; Murahari, Sridhar; Sutayatram, Saikaew; Chew, Dennis J.; Inpanbutr, Nongnuch

doi:10.2460/ajvr.73.8.1262

Cited by 13 publications

(10 citation statements)

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“…Piroxicam in combination with mitoxantrone has a reported objective response rate of 35% and a median survival time of 291 days . Other drugs and drug combinations evaluated, including deracoxib, carboplatin, carboplatin/gemcitabine, cisplatin/firocoxib, vinblastine and metronomic chlorambucil, have modest response rates ranging from 17% to 57% . In a recent randomized clinical trial, no difference was found between carboplatin and mitoxantrone in combination with piroxicam in dogs with TCC …”

Section: Introductionmentioning

confidence: 99%

Expression of receptor tyrosine kinase targets PDGFR‐β, VEGFR2 and KIT in canine transitional cell carcinoma

Walters

Martin

Price

et al. 2017

Vet Comparative Oncology

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Transitional cell carcinoma (TCC) is the most common neoplasia of the canine urinary tract. It tends to be locally invasive and has a moderate metastatic rate. Receptor tyrosine kinases (RTKs) play an important role in promoting cell growth, differentiation and regulation of cell function. RTK inhibitor toceranib phosphate has been used anecdotally to treat TCC. The goal of this study was to evaluate archived normal urinary bladder, TCC and cystitis bladder samples for expression of toceranib phosphate targets: VEGFR2, PDGFR-β and stem cell factor receptor (KIT). A significant number of TCC samples expressed PDGFR-β compared with cystitis and normal bladder samples (P<.0001). While all the tumour samples stained positively for VEGFR2, there was no significant difference between tumour, cystitis and normal bladder samples in intensity scores or staining distribution. Minimal positive staining for KIT was noted in the tumour samples. Based on this proof of target study, further investigation is warranted to determine clinical response of TCC to toceranib phosphate.

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Section: Introductionmentioning

confidence: 99%

Expression of receptor tyrosine kinase targets PDGFR‐β, VEGFR2 and KIT in canine transitional cell carcinoma

Walters

Martin

Price

et al. 2017

Vet Comparative Oncology

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“…The broad range of the herein analyzed cell lines' IC50 values for doxorubicin are comparable with human prostate and bladder cancer cells [77] and with canine mammary carcinoma cells [78]. Concerning carboplatin, the herein characterized TCC cell lines are more sensitive than other canine TCC cell lines [70] and more comparable to human prostate cancer cells [71]. Adcarc1258 and TCC0840 resemble models for multidrug resistance, as they were rather resistant to both doxorubicin and carboplatin.…”

Section: Plos Onementioning

confidence: 61%

“…Cell morphology, doubling time and growth behavior are important and useful information researchers need for experimental design [46,69]. Medical patient data and resistance analysis to classical chemotherapeutic drugs allow assessing the malignancy, multiresistances and the metastatic potential [38,68,70], though chemoresistances are often analyzed in further studies [70][71][72]. However, only three K9TCC cell lines [46] and eight of the herein profiled cell lines were immunohistochemically characterized in direct comparison to the respective original tumor tissue.…”

Section: Plos Onementioning

confidence: 99%

Characterization of six canine prostate adenocarcinoma and three transitional cell carcinoma cell lines derived from primary tumor tissues as well as metastasis

et al. 2020

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Canine prostate adenocarcinoma (PAC) and transitional cell carcinoma (TCC) of prostate and urinary bladder are highly invasive and metastatic tumors of closely neighbored organs. Cell lines are valuable tools to investigate tumor mechanisms and therapeutic approaches in vitro. PAC in dogs is infrequent, difficult to differentiate from TCC and usually characterized by poor prognosis, enhancing the value of the few available cell lines. However, as cell lines adapt to culturing conditions, a thorough characterization, ideally compared to original tissue, is indispensable. Herein, six canine PAC cell lines and three TCC cell lines were profiled by immunophenotype in comparison to respective original tumor tissues. Three of the six PAC cell lines were derived from primary tumor and metastases of the same patient. Further, two of the three TCC cell lines were derived from TCCs invading into or originating from the prostate. Cell biologic parameters as doubling times and chemoresistances to commonly used drugs in cancer treatment (doxorubicin, carboplatin and meloxicam) were assessed. All cell lines were immunohistochemically close to the respective original tissue. Compared to primary tumor cell lines, metastasis-derived cell lines were more chemoresistant to doxorubicin, but equally susceptive to carboplatin treatment. Two cell lines were multiresistant. COX-2 enzyme activity was demonstrated in all cell lines. However, meloxicam inhibited prostaglandin E2 production in only seven of nine cell lines and did neither influence metabolic activity, nor proliferation. The characterized nine cell lines represent excellent tools to investigate PAC as well as TCC in prostate and urinary bladder of the dog. Furthermore, the profiled paired cell lines from PAC primary tumor and metastasis provide the unique opportunity to investigate metastasis-associated changes PAC cells undergo in tumor progression. The combination of nine differently chemoresistant PAC and TCC cell lines resembles the heterogeneity of canine lower urinary tract cancer. Funding: The authors wish to thank the Studienstiftung des Deutschen Volkes for supporting EMP with a scholarship. This publication was supported by Deutsche Forschungsgemeinschaft and University of PLOS ONE Canine prostate and bladder cancer cell lines derived from primary tumor and metastasis PLOS ONE | https://doi.org/10.Original tissue (P = Prostate, B = urinary bladder, Ln = lymph node); cell lines' names are explained as institution (Tiho = University of Veterinary Medicine Hannover); species (D = dog); tissue origin (Pro = prostate; Urt = urinary tract (urinary bladder)); diagnosis (Adcarc = adenocarcinoma; Carc = carcinoma; Metadcarc = metastasis of an adenocarcinoma); abbreviations of cell lines written in bold; none = cell lines have not been published yet; n.a. = tissue of patient no. 5 is missing, as the patient owners declined surgery and necropsy; � diagnosis by cytology of cells obtained by fine needle aspiration biopsy.

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“…These discrepancies could be explained by a non-additive mode of action of the used combinations. In case of gemcitabine and carboplatin synergism is reported for cell line systems (Edelman, Quam & Mullins, 2001; De Brito Galvao et al, 2012; Jin et al, 2013; Tomita et al, 2014). The reason for the false classification in case of docetaxel could be an antagonistic effect, as shown before (Budman, Calabro & Kreis, 2002).…”

Section: Discussionmentioning

confidence: 99%

New in vitro system to predict chemotherapeutic efficacy of drug combinations in fresh tumor samples

Kischkel

Eich

Meyer

et al. 2017

PeerJ

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BackgroundTo find the best individual chemotherapy for cancer patients, the efficacy of different chemotherapeutic drugs can be predicted by pretesting tumor samples in vitro via the chemotherapy-resistance (CTR)-Test®. Although drug combinations are widely used among cancer therapy, so far only single drugs are tested by this and other tests. However, several first line chemotherapies are combining two or more chemotherapeutics, leading to the necessity of drug combination testing methods.MethodsWe established a system to measure and predict the efficacy of chemotherapeutic drug combinations with the help of the Loewe additivity concept in combination with the CTR-test. A combination is measured by using half of the monotherapy’s concentration of both drugs simultaneously. With this method, the efficacy of a combination can also be calculated based on single drug measurements.ResultsThe established system was tested on a data set of ovarian carcinoma samples using the combination carboplatin and paclitaxel and confirmed by using other tumor species and chemotherapeutics. Comparing the measured and the calculated values of the combination testings revealed a high correlation. Additionally, in 70% of the cases the measured and the calculated values lead to the same chemotherapeutic resistance category of the tumor.ConclusionOur data suggest that the best drug combination consists of the most efficient single drugs and the worst drug combination of the least efficient single drugs. Our results showed that single measurements are sufficient to predict combinations in specific cases but there are exceptions in which it is necessary to measure combinations, which is possible with the presented system.

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Effects of gemcitabine and gemcitabine in combination with carboplatin on five canine transitional cell carcinoma cell lines

Abstract: Gemcitabine had antitumor effects on canine TCC cells in vitro, and the combination of gemcitabine and carboplatin had synergistic activity at biologically achievable concentrations.

Cited by 13 publications

References 58 publications

Expression of receptor tyrosine kinase targets PDGFR‐β, VEGFR2 and KIT in canine transitional cell carcinoma

Expression of receptor tyrosine kinase targets PDGFR‐β, VEGFR2 and KIT in canine transitional cell carcinoma

Characterization of six canine prostate adenocarcinoma and three transitional cell carcinoma cell lines derived from primary tumor tissues as well as metastasis

New in vitro system to predict chemotherapeutic efficacy of drug combinations in fresh tumor samples

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