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The aim of this work was to evaluate the possible beneficial effects of a nutraceutical diet on a careless dermal melanoma in an elderly dog. Hemato-biochemical and metabolic parameters as well as clinical symptoms evaluations were performed to monitor the possible improvements of the clinical picture of the dog following a nutraceutical diet supplementation. Hemato-biochemical analyzes and clinical symptoms before nutraceutical diet and after specific diet suspension showed an overall improvement. Moreover, no strong evidence of metastasis after radiographic investigations was observed. This study suggests that clinical status and quality of life (QoL) of an elderly dog affected by dermal melanoma can be positively influenced by a nutraceutical diet supplementation.
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Intern J Appl Res Vet Med • Vol. 16, No. 2, 2018. 117
KEY WORDS: dermal melanoma,
nutraceutical diet, median survival time,
QoL, elderly dog
The aim of this work was to evaluate the
possible benecial effects of a nutraceuti-
cal diet on a careless dermal melanoma in
an elderly dog. Hemato-biochemical and
metabolic parameters as well as clinical
symptoms evaluations were performed
to monitor the possible improvements of
the clinical picture of the dog following a
nutraceutical diet supplementation. Hemato-
biochemical analyzes and clinical symptoms
before nutraceutical diet and after specic
diet suspension showed an overall improve-
ment. Moreover, no strong evidence of
metastasis after radiographic investigations
was observed.
This study suggests that clinical sta-
tus and quality of life (QoL) of an elderly
dog affected by dermal melanoma can be
positively inuenced by a nutraceutical diet
Among canine skin tumors, cutaneous mela-
nomas represent 0.8–2%.1 Multiple factors
affect biological behavior and prognosis of
the melanomas such as:
• tumor site,2
• the mitotic index (three or more mitotic
gures per 10 high-powered elds indi-
cate malignancy),3
• degree of pigmentation,
• necrosis,
• ulceration,
• inammation presence2
Most of cutaneous melanomas in dogs
are benign, with a low mortality rate com-
pared with those occurring in other districts
such as eye, feet/digit and mucosa.4,5 Digit
melanomas have an intermediate progno-
sis and are generally benign. However, an
A Case of Canine Dermal Melanoma: A
Nutraceutical Approach
Sergio Canello1
Gianandrea Guidetti2
Alessandro Di Cerbo3*
Raffaella Cocco4
1Forza10 USA Corp., Research and Development Department, Orlando,
6450 Kingspointe Pkwy Orlando Fl 32819, USA;,
2Research and Development Department, SANYpet S.p.a., 35023 Bagnoli di Sopra,
Padua, Italy; E-mail.
3Department of Medical, Oral and Biotechnological Sciences, Dental School,
University G. d`Annunzio of Chieti-Pescara, Chieti, Italy; E-mail
4Department of Veterinary Medicine, Pathology and Veterinary Clinic Section,
University of Sassari, 07100 Sassari, Italy; E-mail.
(*) Corresponding author: Alessandro Di Cerbo,
Department of Medical, Oral and Biotechnological Sciences, Dental School,
University G. D`Annunzio of Chieti-Pescara, Chieti, Italy;
E-mail.; Ph. +393923731318
Vol. 16, No.2, 2018 • Intern J Appl Res Vet Med.
epidemiologic survey from Spangler et al
(2006) revealed that feet melanomas have
a diagnosis of malignancy in 74% of the
cases, a recurrence or possibility to metas-
tasize of 38% and a median survival time of
158 days.
Elective treatments for melanomas are
surgical excision or systemic chemotherapy.6
However, molecular targeted therapies, e.g,
receptor tyrosine kinase (RTK) inhibitors,7
IFN-α 8, and cancer vaccines 9,10 have gained
great attention.
To the best of our knowledge, this is the
rst case of an elderly dog treated with a
commercially available nutraceutical diet for
a right hind paw malignant melanoma. The
nutraceutical diet consisted in a commercial
mixed formula based on sh proteins, rice
carbohydrates, Cucumis melo, Ascophyllum
nodosum, Hematococcus pluvialis, Aloe
vera, Carica papaya, Punica granatum,
Camellia sinensis, Polygonum cuspida-
tum, Curcuma longa, Piper nigrum, zinc,
and a Omega3/6 ratio of 1:0.8, which was
already proven to signicantly decrease
type 1 helper T lymphocyte (Th1) cells and
increase T regulatory (Treg) cells in dogs
affected by Leishmania infantum11, signi-
cantly improve clinical signs and symptoms
of canine keratoconjunctivitis sicca 12 and
exert a signicant anti-inammatory activity
in vitro.13
On September 2014, a 13-years-old male
mixed breed dog presented to the veterinary
Hospital of the University of Sassari for
treatment of asthenia, increased weight, and
appetite loss.
Physical examination revealed bright-
ness, poor responsiveness and altered vital
parameters (T = 37.6 °C, P = 65 bpm, RR =
18 brpm). A 17 cm, haired mass raised over
the dog’s right hind paw was noted (Figure
A biopsy revealed malignant mela-
noma with approximately 3 mitoses per
10 high-powered elds (HPF). Generally,
mucocutaneous junctions and glabrous skin
lesions refer to malignant forms, while the
others are considered as benign. In this case
the presence of atypical pleomorphic nuclei
(multiple nucleoli) lay for a malignant form
despite the low proliferative activity (Figure
2). The work-up for the dog also included
hemato-biochemical and metabolic analysis,
three-view thoracic radiographs, and ab-
dominal ultrasound in order to obtain a base-
line health status on the dog. Initial blood
exam and serum proteins electrophoresis
evidenced a slight lymphopenia (19.4%, ref.
val. 25-50%) and an alfa2 and beta2 frac-
Figure 1. Clinical pictures of right hind paw melanoma. (a) A 17 cm haired, stiff and homoge-
neous mass before and (B) after (13 cm) 2 months of nutraceutical treatment.
Intern J Appl Res Vet Med • Vol. 16, No. 2, 2018. 119
tions increase (16.4%, ref. val. 7.9-13.0%;
36.3%, ref. val. 11.5 - 23.2%; respectively).
None of the metabolic prole parameters
resulted altered.
In spite of the need for surgical excision
of the mass to reduce the risk of metastasis,
the advanced age, the low survival rate after
a surgical intervention, and the previous un-
successful pharmacological treatments come
out in favor of a nutraceutical approach.
After 1 month of nutraceutical diet
administration, a normalization of lympho-
cytes was observed, while the alfa2 and
beta2 fractions increase still persisted.
The same trend was observed after 3
months of nutraceutical diet supplementa-
tion. After 5 months, the metabolic prole
showed a total bilirubin and CPK increase
(1.18 mg/dl, ref. val. 0.11- 0.31 mg/dl; 279
U/l, ref. val. 42-155 U/l; respectively),
while a decrease of alfa1 (2.2%, ref. val.
2.6 - 4.5%) and an increase in alfa2, beta,
and gamma were observed (14.0, ref. val.
7.9 - 13.0; 33.0%, ref. val. 11.5 - 23.2% and
14.6%, ref. val. 6.5 - 14.0%; respectively).
Due to the reduced metabolic require-
ments of the dog, the nutraceutical diet was
suspended and a specic diet for elderly
dogs was administered. A further increase
of CPK, creatinine, P, GOT, and Mg was
observed (540 U/l, ref. val. 42-155 U/l; 1.69
mg/dl ref. val. 0.8- 1.42 mg/dl; 11.3 mg/dl,
ref. val. 2- 3.5 mg/dl; 82 U/l ref. val. 21-44
U/l; 2.35 mg/dl ref. val. 0.67-0.94 mg/dl;
respectively). Hence, the diet was suspended
and the nutraceutical diet reintroduced. After
3 months CPK, creatinine, P, GOT, and Mg
resulted decreased within normal range.
The three-view radiographs were clini-
cally normal and negative for metastasis.
The abdominal ultrasound revealed a dif-
fusely, mildly enlarged spleen with normal
echogenicity. Based on these ndings,
there was no strong evidence of metastasis
and overall the dog appeared to be in good
Figure 2. Photomicrograph of right hind paw melanoma. Presence of atypical pleomorphic
nuclei (multiple nucleoli) at different magnications (a-b) 4x, (c) 10x, (d) 20x.
Vol. 16, No.2, 2018 • Intern J Appl Res Vet Med.
Physical exams and diagnostic tests were
also repeated 6, 12 and 24 months since
nutraceutical diet supplementation begin.
Unfortunately, after 26 months since
nutraceutical diet supplementation, the dog
died due to a rapid worsening of clinical
The initial lymphopenia might be ascribed to
the right hind paw lesion. In fact, it is typical
of an acute inammatory status or infec-
tions, mostly viral. The metabolic prole did
not evidence any alteration. Therefore, the
appetite loss, the consequent slimming and
asthenia, as well as the breath frequency in-
crease might be the consequence of the pain/
complaint derived by the lesion. Physical
exam did not show any alteration of the car-
diocirculatory and respiratory system. Also,
the increase of alfa2 globulins might be
referred to the presence of the lesion, while
the increase of beta globulins was linked to
the overall inammatory status.
The signicant reduction of the lesion
dimensions (~24%) was a clear evidence of
the anti-inammatory activity exerted by the
nutraceutical diet 14,15, as well as the normal-
ization of the blood exam and appetite. After
5 months, the reduction of blood cells count
and hemoglobin and the increase of bilirubin
addressed toward the diagnosis of hemolytic
The metabolic parameters variations led
to a suspension of the nutraceutical diet due
to its metabolizable energy content, which
was higher with respect to that recommend-
ed for an elderly dog. The new hemato-
biochemical analyzes revealed the onset of a
kidney insufciency, preannounced by clini-
cal symptoms such as appetite loss, polyuria,
and polydipsia. Therefore, the nutraceutical
diet was reintroduced. After 3 months, all
hematological parameters resulted improved
along with clinical symptoms, thus demon-
strating the good tolerability of the diet de-
spite the high metabolizable energy content.
In conclusion, the introduction of a
nutraceutical diet resulted particularly effec-
tive in extending the median survival time
of an elderly dog right hind paw melanoma,
improving the hematological parameters and
related clinical symptoms and consequently
the QoL.
The authors hereby certify that all work con-
tained in this article is original. The authors
claim full responsibility for the contents of
the article.
The authors certify that there is no conict
of interest with any nancial organization
regarding the material discussed in the
manuscript. This research was performed
in collaboration with some scientists from
the Division of Research and Development,
Sanypet SpA, Padua, Italy (as indicated in
the Author’s afliation) according to scien-
tic and ethical principles of the scientic
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... Blood fatty acid composition could be used as a biomarker of dietary intake and could be an important parameter to understand the relationship between diet, metabolism, and some diseases. Some fatty acids (FA), such as polyunsaturated fatty acids (PUFA), have a potential role in the prevention of several diseases, such as atherosclerosis, cancer, and inflammation [1][2][3][4][5][6][7][8]. A positive correlation between the total content of dietary PUFA in the diet and the relative amount of PUFA in the blood lipid fraction has been documented in humans [9,10] and animals [11]. ...
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The aim of this study was to evaluate the effect of fish (FH) and chicken (CH) diets and the combination of these with a supplementation with antioxidant compounds (FH-AOX and CH-AOX, respectively), on biochemical parameters and blood fatty acid (FA) profile. For this purpose, 27 dogs were allocated to four groups and fed with the experimental diets for six months. Blood samples were taken before starting the experimental period and at the end of the trial. Dietary treatment effects were assessed by ANOVA test. The antioxidant supplement increased glucose values, independently of the type of meat. Triglycerides and urea were significantly higher in FH compared to CH diet. As regard blood FA profile, the antioxidant supplementation significantly increased the linoleic acid content. Polyunsaturated FA n-3 were higher in FH than CH, but a greater increase was recorded in the two groups with the addition of antioxidant. On the contrary, arachidonic acid was found lower in the two groups fed the antioxidant compounds. In conclusion, FH led to a better FA profile than CH diet. In addition, the use of antioxidant supplement was able to improve the FA profile independently on the basal diet.
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Functional foods provide health benefits if they are consumed on a regular basis as part of a varied diet. In this review, we discuss the availability and role of functional foods in pet nutrition with a focus on dogs and cats. Indeed functional foods modify gastrointestinal physiology, promote changes in biochemical parameters, improve brain functions and may reduce or minimize the risk to develop specific pathologies. This evidence derives largely from clinical studies while only limited evidence from studies in dogs and cats is available. Therefore, functional food consumption should be further investigated in pet nutrition to understand how dietary interventions can be used for disease prevention and treatment.
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BACKGROUND:Canine keratoconjunctivitis sicca (cKCS) is an inflammatory eye condition related to a deficiency in the tear aqueous fraction. Etiopathogenesis of such disease is substantially multifactorial, combining the individual genetic background with environmental factors that contribute to the process of immunological tolerance disruption and, as a consequence, to the emergence of autoimmunity disease. In this occurrence, it is of relevance the role of the physiological immune-dysregulation that results in immune-mediated processes at the basis of cKCS. Current therapies for this ocular disease rely on immunosuppressive treatments. Clinical response to treatment frequently varies from poor to good, depending on the clinical-pathological status of eyes at diagnosis and on individual response to therapy. In the light of the variability of clinical response to therapies, we evaluated the use of an anti-inflammatory/antioxidant nutraceutical diet with potential immune-modulating activity as a therapeutical adjuvant in cKCS pharmacological treatment. Such combination was administered to a cohort of dogs affected by cKCS in which the only immunosuppressive treatment resulted poorly responsive or ineffective in controlling the ocular symptoms. RESULTS: Fifty dogs of different breeds affected by immune-mediated cKCS were equally distributed and randomly assigned to receive either a standard diet (control, n = 25) or the nutraceutical diet (treatment group, n = 25) both combined with standard immunosuppressive therapy over a 60 days period. An overall significant improvement of all clinical parameters (tear production, conjunctival inflammation, corneal keratinization, corneal pigment density and mucus discharge) and the lack of food-related adverse reactions were observed in the treatment group (p < 0.0001). CONCLUSIONS: Our results showed that the association of traditional immune-suppressive therapy with the antioxidant/anti-inflammatory properties of the nutraceutical diet resulted in a significant amelioration of clinical signs and symptoms in cKCS. The beneficial effects, likely due to the presence of supplemented nutraceuticals in the diet, appeared to specifically reduce the immune-mediated ocular symptoms in those cKCS-affected dogs that were poorly responsive or unresponsive to classical immunosuppressive drugs. These data suggest that metabolic changes could affect the immune response orchestration in a model of immune-mediated ocular disease, as represented by cKCS.
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The aim of this evaluation study was to assess the possible role of a specific nutraceutical diet in relieving main clinical symptoms of chronic bilateral otitis externa (occlusion of ear canal, erythema, discharge quantity, and odor) in 30 adult dogs. Thirty dogs of different breeds (mean age ± SEM; 6.03 ± 0.15 years and mean weight ± SEM; 32.01 ± 1.17 Kg; 53.3 % males, 46.6 % females) with evident chronic clinical otitis symptoms were equally divided and randomly assigned to receive either the nutraceutical diet (ND group) or a standard diet (SD group) over a period of 90 days. In all cases a topical pharmacological treatment was given. The nutraceutical diet, also endowed with anti-inflammatory and antioxidant activities, significantly decreased the mean score intensity of all symptoms after 90 days of intervention (P < 0.0001) with the exception of Malassezia pachydermatis infection which was only slightly reduced. Our investigation is one of the few evidence-based results where a commercial nutraceutical diet has been proven effective, in combination with drugs, in relieving otitis externa-related symptoms. This study opens new insights into otitis externa clinical management providing evidence of efficacy of a combined therapy with drugs and a specific nutraceutical diet.
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Background Clinical appearance and evolution of Canine Leishmaniosis (CL) are the consequence of complex interactions between the parasite and the genetic and immunological backgrounds. We investigated the effect of an immune-modulating diet in CL. Dogs were treated with anti- Leishmania pharmacological therapy combined with standard diet (SD Group) or with the immune-modulating diet (IMMD Group). CD3+ CD4+ Foxp3+ Regulatory T cells (Treg) and CD3+ CD4+ IFN-γ + T helper 1 (Th1) were analyzed by flow cytometry. Results All sick dogs showed low platelet number at diagnosis (T0). A platelet increase was observed after six months (T6) SD Group, with still remaining in the normal range at twelve months (T12). IMMD Group showed an increase in platelet number becoming similar to healthy dogs at T6 and T12. An increase of CD4/CD8 ratio was revealed in SD Group after three months (T3), while at T6 and at T12 the values resembled to T0. The increase in CD4/CD8 ratio at T3 was maintained at T6 and T12 in IMMD Group. A reduction in the percentage of Treg of all sick dogs was observed at T0. A recovery of Treg percentage was observed only at T3 in SD Group, while this effect disappeared at T6 and T12. In contrast, Treg percentage became similar to healthy animals in IMDD Group at T3, T6 and T12. Sick dogs showed an increase of Th1 cells at T0 as compared with healthy dogs. We observed the occurrence of a decrease of Th1 cells from T3 to T12 in SD Group, although a trend of increase was observed at T6 and T12. At variance, IMMD Group dogs showed a progressive decrease of Th1 cells, whose levels became similar to healthy controls at T6 and T12. Conclusion The immune-modulating diet appears to regulate the immune response in CL during the standard pharmacological treatment. The presence of nutraceuticals in the diet correlates with the decrease of Th1 cells and with the increase of Treg in sick dogs. Therefore, the administration of the specific dietary supplement improved the clinical response to the standard treatment in a model of CL.
Recent investigations have highlighted the controversial role of Wnt/β-catenin pathway activation in human cutaneous melanoma. Survivin has been proposed as a valid prognostic marker for invasive and metastatic melanomas and lymph node melanoma metastasis in human cutaneous melanoma and is a promising therapeutic target. Our aim was to investigate the immunohistochemical expression of survivin and β-catenin in canine cutaneous melanocytic tumours, in order to understand their prognostic significance. Twenty-one melanocytic tumours (10 melanocytomas and 11 melanomas) were investigated by immunohistochemistry using specific anti-survivin and anti-β-catenin antibodies. A semi-quantitative method was used to analyse the results; β-catenin immunolabelling in neoplastic cells was evaluated as cytoplasmic, membranous or nuclear. The number of survivin-positive cells was counted within ~1000 neoplastic cells. Results were related to histopathological features, evaluated in haematoxylin- and eosin-stained slides, and to the clinical data obtained through a telephone survey with referring veterinarians. Despite a low level of expression in the majority of cases, β-catenin was found to be correlated strongly with malignant behaviour (P < 0.01). An overexpression of nuclear survivin was statistically related to histological features of malignancy, presence of metastasis and death related to melanoma spread (P < 0.01). The low nuclear β-catenin expression, mainly found in metastatic cases, would indicate that β-catenin activation may have only limited importance in the development or progression of canine cutaneous melanoma. The correlation of nuclear survivin expression with malignancy would indicate that survivin is possibly a useful prognostic marker and therapeutic target in canine melanoma patients. © 2015 ESVD and ACVD.
Skin cancer is one of the most commonly diagnosed cancers in the world today in both humans and our pet population. Advances in molecular techniques are now affording us an opportunity to develop therapeutics targeted at specific cancer-related cellular pathways. However, despite progress in conventional treatments, such as chemotherapy and radiation, and the new targeted therapies, some cancers, such as melanoma and cutaneous lymphoma, continue to cause significant mortality and morbidity. This short synopsis is not complete but is aimed at providing an insight into current advanced treatments and horizon therapies for cutaneous malignancies in dogs and cats with comparative aspects.