scholarly journals Canine Melanomas as Models for Human Melanomas: Clinical, Histological, and Genetic Comparison

Genes ◽  
2019 ◽  
Vol 10 (7) ◽  
pp. 501 ◽  
Author(s):  
Prouteau ◽  
André
Keyword(s):  
Human Melanoma ◽  
Translational Model ◽  
Comparative Oncology ◽  
Genetic Characteristics ◽  
Malignant Melanomas ◽  
Therapeutic Trials ◽  
Naturally Occurring ◽  
Preclinical Trials ◽  
Canine Models ◽  
Melanoma Subtypes

Despite recent genetic advances and numerous ongoing therapeutic trials, malignant melanoma remains fatal, and prognostic factors as well as more efficient treatments are needed. The development of such research strongly depends on the availability of appropriate models recapitulating all the features of human melanoma. The concept of comparative oncology, with the use of spontaneous canine models has recently acquired a unique value as a translational model. Canine malignant melanomas are naturally occurring cancers presenting striking homologies with human melanomas. As for many other cancers, dogs present surprising breed predispositions and higher frequency of certain subtypes per breed. Oral melanomas, which are much more frequent and highly severe in dogs and cutaneous melanomas with severe digital forms or uveal subtypes are subtypes presenting relevant homologies with their human counterparts, thus constituting close models for these human melanoma subtypes. This review addresses how canine and human melanoma subtypes compare based on their epidemiological, clinical, histological, and genetic characteristics, and how comparative oncology approaches can provide insights into rare and poorly characterized melanoma subtypes in humans that are frequent and breed-specific in dogs. We propose canine malignant melanomas as models for rare non-UV-induced human melanomas, especially mucosal melanomas. Naturally affected dogs offer the opportunity to decipher the genetics at both germline and somatic levels and to explore therapeutic options, with the dog entering preclinical trials as human patients, benefiting both dogs and humans.

scholarly journals Clinical, Pathological, and Ethical Considerations for the Conduct of Clinical Trials in Dogs with Naturally Occurring Cancer: A Comparative Approach to Accelerate Translational Drug Development

ILAR Journal ◽  
2018 ◽  
Vol 59 (1) ◽  
pp. 99-110 ◽  
Author(s):  
Daniel Regan ◽  
Kelly Garcia ◽  
Douglas Thamm
Keyword(s):  
Clinical Trials ◽  
Drug Development ◽  
Translational Research ◽  
Cancer Biology ◽  
Comparative Approach ◽  
Cancer Drug ◽  
Comparative Oncology ◽  
Pet Dogs ◽  
Naturally Occurring

Abstract The role of comparative oncology in translational research is receiving increasing attention from drug developers and the greater biomedical research community. Pet dogs with spontaneous cancer are important and underutilized translational models, owing to dogs’ large size and relative outbreeding, combined with their high incidence of certain tumor histotypes with significant biological, genetic, and histological similarities to their human tumor counterparts. Dogs with spontaneous tumors naturally develop therapy resistance and spontaneous metastasis, all in the context of an intact immune system. These fundamental features of cancer biology are often lacking in induced or genetically engineered preclinical tumor models and likely contribute to their poor predictive value and the associated overall high failure rate in oncology drug development. Thus, the conduct of clinical trials in pet dogs with naturally occurring cancer represents a viable surrogate and valuable intermediary step that should be increasingly incorporated into the cancer drug discovery and development pipeline. The development of molecular-targeted therapies has resulted in an expanded role of the pathologist in human oncology trials, and similarly the expertise of veterinary pathologists will be increasingly valuable to all phases of comparative oncology trial design and conduct. In this review, we provide a framework of clinical, ethical, and pathology-focused considerations for the increasing integration of translational research investigations in dogs with spontaneous cancer as a means to accelerate clinical cancer discovery and drug development.

scholarly journals Naturally Occurring Canine Melanoma as a Predictive Comparative Oncology Model for Human Mucosal and Other Triple Wild-Type Melanomas

2018 ◽  
Vol 19 (2) ◽  
pp. 394 ◽  
Author(s):  
Belen Hernandez ◽  
Hibret Adissu ◽  
Bih-Rong Wei ◽  
Helen Michael ◽  
Glenn Merlino ◽  
...  
Keyword(s):  
Wild Type ◽  
Comparative Oncology ◽  
Naturally Occurring ◽  
Canine Melanoma

scholarly journals Biological significance of naturally occurring deuterium: the antitumor effect of deuterium depletion

2010 ◽  
Vol 151 (36) ◽  
pp. 1455-1460 ◽  
Author(s):  
Gábor Somlyai ◽  
Miklós Molnár ◽  
Gábor Laskay ◽  
Mariann Szabó ◽  
Tamás Berkényi ◽  
...  
Keyword(s):  
Antitumor Effect ◽  
Biological Significance ◽  
Human Melanoma ◽  
Naturally Occurring ◽  
Ht 29 ◽  
Mcf 7

A felszíni vizekben a deutérium (D) koncentrációja több mint 16 mmol/l (150 ppm), az élő szervezetekben 10 mmol/l fölötti. A csökkentett deutériumtartalmú (30±5 ppm) vízzel folyó kutatások során korábban azt tapasztalták, hogy a deutériummegvonás gátolta a sejtosztódást in vitro különböző tumoros sejtvonalakban (PC-3, humán prosztatatumor; MDA, humán emlőtumor; HT-29, humán vastagbéltumor; M14, humán melanoma). A csökkentett deutériumtartalmú víz tumorregressziót idézett elő humán eredetű tumorral xenotranszplantált, immunszuppresszált egerekben (MDA és MCF-7 humán emlőtumor, PC-3 prosztatatumor), és apoptózist indukált in vitro és in vivo . A csökkentett deutériumtartalmú víz (25±5 ppm) részleges vagy teljes tumorregressziót idézett elő spontán tumoros kutyákban és macskákban. A készítményt 1999-ben daganatellenes állatgyógyszerként törzskönyvezték (Vetera-DDW-25 A.U.V., 13/99 FVM). Injekciós változatát klinikai vizsgálatban sikeresen tesztelték. Az Országos Gyógyszerészeti Intézet 5621/40/95 számú engedélye alapján, a GCP-elvek betartásával lefolytatott randomizált, kettős vak elrendezésű humán fázis II klinikai vizsgálat szignifikáns különbséget igazolt a kontroll- és a kezelt csoport között a vizsgált paraméterek vonatkozásában. Egyéves utánkövetés során a csökkentett deutériumtartalmú víz szignifikánsan csökkentette a prosztatatumoros betegek halálozási arányát, miközben a túlélés hosszát szignifikánsan növelte. Az eredmények azt igazolják, hogy a sejtek képesek szabályozni a deutérium/hidrogén (D/H) arányát és ennek változtatásával elindítani bizonyos molekuláris folyamatokat, amelyeknek kulcsszerepük van a sejtciklus szabályozásában. Feltételezzük, hogy nem az intracelluláris pH változása, hanem az azt kísérő D/H arány változása adja meg a sejteknek a jelet az S-fázisba lépéshez. A D-koncentráció csökkenése beavatkozik a szignáltranszdukciós folyamatokba, így idézve elő a tumor regresszióját. A D szerepének felismerése a sejtosztódás szabályozásában új lehetőségeket nyit meg a daganatterápia és a megelőzés területén, hozzájárulva ezzel a jelenlegi daganatellenes terápiák hatékonyságának növeléséhez.

scholarly journals Development and Genetic Characteristics of the Selkirk Rex Cats

2020 ◽  
Vol 9 (3) ◽  
pp. 7
Author(s):  
Min Wang
Keyword(s):  
Genetic Characteristics ◽  
Naturally Occurring ◽  
Long Line ◽  
In Captivity

The Selkirk Rex is one of the four curly cats and is the latest in a long line of natural breeds. Naturally occurring cat breeds, unlike those that have been bred in captivity, appear without any human involvement.

scholarly journals Naturally-Occurring Canine Mammary Tumors as a Translational Model for Human Breast Cancer

2020 ◽  
Vol 10 ◽  
Author(s):  
Mark Gray ◽  
James Meehan ◽  
Carlos Martínez-Pérez ◽  
Charlene Kay ◽  
Arran K. Turnbull ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Human Breast Cancer ◽  
Mammary Tumors ◽  
Human Breast ◽  
Translational Model ◽  
Naturally Occurring ◽  
Canine Mammary Tumors

Targeting Src/Stat3 pathway in malignant melanoma

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 8025-8025
Author(s):  
J. Homsi ◽  
J. Messina ◽  
C. Cubutt ◽  
S. Maunglay ◽  
L. Scalf ◽  
...  
Keyword(s):  
Cell Lines ◽  
Melanoma Cell ◽  
Topoisomerase I ◽  
Chemotherapeutic Agents ◽  
Human Melanoma ◽  
Variable Expression ◽  
Src Inhibitor ◽  
Melanoma Subtypes ◽  
Chemotherapy Agents ◽  
Melanoma Cell Lines

8025 Background: The Src/Stat 3 pathway has been implicated in the pathogenesis of several malignancies including melanoma. In the current study we evaluated the prevalence of Src and Stat3 activation in human melanoma and the effect of Src inhibitors alone or in combination with chemotherapeutic agents on melanoma cell lines. Methods: Activation of Src was measured by staining for Src-phosphotyrosine 416 (P-Src) and Stat3 by phosphotyrosine 705 Stat3 (P-Stat3). Immunohistochemistry was performed with anti-pStat3-Y705 and anti-pSrc-Y416 antibodies (Cell Signaling, Beverly, MA) on 3 melanoma subtypes. Staining of tumor cells for P-Stat3 was scored by percentage of stained cells as follows: 0 (no staining), 1 (1–25%), 2 (26–50%), 3 (>50%), and intensity 0–3 (0: absent, 1: low, 2: moderate, and 3: high). The sum of these was the composite P-Stat3 score: 0 (0), 1 (1–2), 2 (3–4), and 3 (5–6). P-Src staining was scored by intensity. Melanoma cell lines, A-375, SK-Mel-5 and SK-Mel-28 were exposed to Src inhibitors, SKI-606, PD 180970 and BMS 354825 alone or in combination with standard chemotherapy agents and IC-50 was determined by MTT assay at 24 and 72 hours. Results: 35 biopsies were stained. Median age was 66 years (range 23–90); 60% were women. 48% of all melanoma stained express P-Src; all samples express pStat3. We found a positive correlation between P-Src and P-Stat3 (Spearman coefficient=0.346, p=0.042). 46% stained only for pStat3 and 6% did not stain for either P-Src or P-Stat3. Most positively stained biopsies stained weakly for P-Src and moderately or strongly for pStat3. Src inhibitors inhibited the proliferation of melanoma cell lines; furthermore Src inhibitor treatment synergized with platinum and topoisomerase I inhibitors but not temozolomide. Conclusions: 1) Immunohistochemistry shows variable expression of P-Src and P-Stat3 in human melanoma 2) All tumors staining for P-Src also stain for P-Stat3 and the strength of staining is significantly related. 3) This data may be useful in planning future clinical trials with Src inhibitors in melanoma. [Table: see text] [Table: see text]

scholarly journals Mammalian Models of Duchenne Muscular Dystrophy: Pathological Characteristics and Therapeutic Applications

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Akinori Nakamura ◽  
Shin'ichi Takeda
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Animal Models ◽  
Viral Vectors ◽  
Exon Skipping ◽  
Therapeutic Applications ◽  
Gene Therapies ◽  
Therapeutic Trials ◽  
Canine Models ◽  
Pharmaceutical Agents

Duchenne muscular dystrophy (DMD) is a devastating X-linked muscle disorder characterized by muscle wasting which is caused by mutations in theDMDgene. TheDMDgene encodes the sarcolemmal protein dystrophin, and loss of dystrophin causes muscle degeneration and necrosis. Thus far, therapies for this disorder are unavailable. However, various therapeutic trials based on gene therapy, exon skipping, cell therapy, read through therapy, or pharmaceutical agents have been conducted extensively. In the development of therapy as well as elucidation of pathogenesis in DMD, appropriate animal models are needed. Various animal models of DMD have been identified, and mammalian (murine, canine, and feline) models are indispensable for the examination of the mechanisms of pathogenesis and the development of therapies. Here, we review the pathological features of DMD and therapeutic applications, especially of exon skipping using antisense oligonucleotides and gene therapies using viral vectors in murine and canine models of DMD.

Feline mammary tumours in comparative oncology

2005 ◽  
Vol 72 (S1) ◽  
pp. 98-106 ◽  
Author(s):  
Valentina Zappulli ◽  
Gabrita De Zan ◽  
Barbara Cardazzo ◽  
Luca Bargelloni ◽  
Massimo Castagnaro
Keyword(s):  
Large Population ◽  
Companion Animals ◽  
Domestic Animals ◽  
Rapid Progression ◽  
Comparative Oncology ◽  
Skin Tumours ◽  
Naturally Occurring ◽  
High Incidence ◽  
Therapeutic Tools ◽  
Similar Risk

Naturally occurring tumours in domestic animals have been recognized as an interesting opportunity for comparative oncology (MacEwen, 1990; Vail & MacEwen, 2000). Cancer is the second most frequent cause of death in humans and the first one in dogs and cats (Jemal et al. 2003). The age-adjusted overall cancer incidence per 100000 individuals per year is comparable in humans and domestic animals, being approximately 300 in humans, 381 in dogs and 264 in cats (Vail & MacEwen, 2000). When analysing the incidence by site, breast cancer is the most frequent (32%) in women, the first of all neoplasia (52%) occurring in bitches and the third (17%) in queens after lymphohaemopoietic and skin tumours (Hayes et al. 1981; Hayes & Mooney, 1985; MacEwen, 1990; MacEwen & Withrow, 1996; Jemal et al. 2003). Several other aspects contribute to the value of domestic animals as models for human cancers (MacEwen, 1990; Vail & MacEwen, 2000). Tumours occur spontaneously in companion animals that share a similar environment with humans and therefore might be exposed to similar risk factors. The high incidence of some tumour types offers large population samples. The shorter overall lifespan of domestic animals associated with a more rapid progression of cancer allows adequate comparison of response time with humans. Biological, anatomical, histopathological, genetic, and molecular similarities between some animal and human tumours are also well established (Hansen & Khanna, 2004). Finally, testing novel therapies is more ethically acceptable when treating spontaneous diseases in companion animals rather than experimentally induced pathologies in animal models. At the same time, there is an increasing interest of owners towards the use of the most advanced therapeutic tools for companion animals despite the higher economic costs associated with these therapies.

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