A retrospective study of chemotherapeutic effect without wide-margin surgery or radiation therapy in dogs with oral malignant melanoma.

Background: Effective treatment for canine oral malignant melanoma (e.g., curative-intent surgery) may not be feasible or radiation therapy may be unavailable. However, chemotherapy is usually an option, and more information is needed regarding its use without adequate local treatments. Objective: Our objective was to investigate the efficacy of chemotherapy in canine oral malignant melanoma without adequate local control, using carboplatin with dose reduction in small-breed dogs and metronomic chemotherapy. Animals and procedure: Client-owned dogs with histopathologically diagnosed oral malignant melanoma were retrospectively enrolled from 2016 to 2022. The chemotherapy protocol in each case was determined by the attending clinician. Results: Thirteen dogs were included. The median progression-free interval of all 13 dogs was 42 d (14 to 953 d). The median overall survival time of dogs with chemotherapy as their only systemic treatment was 181 d (50 to 960 d; n = 11). The median dosage of carboplatin was 250 mg/m2. Response to treatment and clinical stage were significant prognostic factors. Conclusion and clinical relevance: As chemotherapy provided a median survival of 6 mo, it could be considered when adequate local control is infeasible. Earlier clinical stages or achievement of at least stable disease during chemotherapy may indicate better survival in dogs.

Une étude rétrospective de l'effet chimiothérapeutique sur le mélanome malin buccal canin dépourvu de chirurgie et de radiothérapie á large marge : le stade clinique et la réponse au traitement prédisent les résultats du patient. Mise en contexte: Des traitements efficaces pour le mélanome malin oral canin, tels que la chirurgie á visée curative, ne sont parfois pas réalisables ou la radiothérapie n'est pas disponible dans certaines régions. La chimiothérapie reste une option de traitement et davantage d'informations devraient être fournies pour les cas qui n'ont pas eu accés á un traitement local adéquat. Objectif: Cette étude visait á étudier l'efficacité de la chimiothérapie dans le mélanome malin oral canin sans contrôle local adéquat, en utilisant le carboplatine avec réduction de dose chez les chiens de petite race et la chimiothérapie métronomique. Animaux et procédure: Treize chiens appartenant á des clients atteints d'un mélanome malin oral diagnostiqué par histopathologie ont été rétrospectivement inscrits de 2016 á 2022. Le protocole de chimiothérapie a été déterminé par le clinicien traitant. Résultats: L'intervalle médian sans progression des treize chiens était de 42 jours (14­953 jours). La durée médiane de survie globale des chiens ayant reçu une chimiothérapie comme seul traitement systémique était de 181 jours (50­960 jours; n = 11). La dose médiane de carboplatine était de 250 mg/m2. La réponse au traitement et le stade clinique étaient des facteurs pronostiques importants. Conclusion et pertinence clinique: La chimiothérapie pouvait encore être envisagée lorsqu'un contrôle local adéquat était impossible. Des stades cliniques plus précoces ou des patients atteignant au moins une maladie stable pendant la chimiothérapie peuvent indiquer une meilleure survie.(Traduit par les auteurs).

Limited Clinical Efficacy with Potential Adverse Events in a Pilot Study of Autologous Adoptive Cell Therapy in Canine Oral Malignant Melanoma.

Adoptive cell therapy (ACT) has been studied in several human and canine cancers with some promising clinical outcomes but not in canine oral malignant melanoma (OMM). Our manuscript aimed to explore one kind of ACT, the ex vivo-expanded autologous immune cell infusion in canine OMM, as this tumor remains a treatment dilemma. The study recruited dogs with histopathological diagnoses of oral malignant melanoma, generated their peripheral blood mononuclear cells, expanded them into predominantly non-B non-T cells via stimulations of IL-15, IL-2, and IL-21, and then re-infused the cells into tumor-bearing dogs. Ten dogs were enrolled; three dogs did not report any adverse events; three had a mildly altered appetite; one had a mildly increased liver index, while the other three developed suspected anaphylaxis at different levels. The median progression-free interval was 49 days. Dogs with progressive disease during treatment had a shorter survival. This pilot study indicates limited efficacy with potential adverse events of this ACT. Most recruited patients were in a later stage and had macroscopic disease, which might affect the treatment efficacy. Further exploration of this cell therapy in an adjuvant setting, with adequate protocol modification and standardization, could still be considered.

Investigation of Toxoplasma infection in zoo animals using multispecies ELISA and GRA7 nested PCR.

BACKGROUND: Toxoplasma is an obligate intracellular protozoan that causes an important zoonotic disease with a worldwide distribution. Felids are the definitive hosts of this parasite, while virtually all warm-blooded animals, including birds, serve as intermediate hosts. Four ring-tailed lemurs (Lemur catta) in the Taipei Zoo died of acute Toxoplasma infection in June 2019. Since then, Toxoplasma has occasionally been identified in this Zoo during necropsy of dead animals and PCR of animal blood samples. Therefore, a general survey of Toxoplasma infection in animals in the Zoo seems to be needed. METHODS AND RESULTS: An indirect multispecies ELISA was used for the first time to screen for Toxoplasma infection in 326 serum samples collected from 75 species of animals. The infection rate of Toxoplasma was 27% (88/326). A commercial latex agglutination (LAT) assay was used to re-examine the samples with doubtful and uncertain ELISA results (151 samples from 42 species). The infection rate increased to 36.2% (118/326), and the indirect multispecies ELISA appeared to be applicable to 31 of 75 species animals included in this study. Nested PCR assays targeting the dense granule protein 7 (GRA7) gene and B1 gene were also used to detect Toxoplasma in DNA samples extracted from 10 liver or blood specimens from 8 animals. GRA7 gene fragments were amplified from 8 samples from 7 animals, while B1 gene fragments were amplified from only 4 samples from 4 animals. From the B1 nested PCR and the sequence data of GRA7 fragments amplified from infectious specimens, the animals in the Zoo were speculated to have been infected by at least three different Toxoplasma variants. CONCLUSIONS: According to the serological investigation, we speculated that over one-third (36.2%) of animals in Taipei Zoo presented the infection of Toxoplasma, and the indirect multispecies ELISA we used can be applied to detect Toxoplasma infection in 31 animal species included in this study. Sequence analysis revealed that at least three Toxoplasma variants were infecting the animals of Taipei Zoo.

L-Asparaginase, Doxorubicin, Vincristine, and Prednisolone (LHOP) Chemotherapy as a First-Line Treatment for Dogs with Multicentric Lymphoma.

Cyclophosphamide exhibits the weakest therapeutic effect compared with vincristine and doxorubicin in the CHOP (C, cyclophosphamide; H, doxorubicin; O, vincristine; and P, prednisolone) chemotherapeutic protocol for the treatment of canine lymphoma. Twenty dogs with multicentric lymphoma were treated using the LHOP protocol, which used l-asparaginase in place of cyclophosphamide, and the outcomes were historically compared with those of dogs that received CHOP chemotherapy in the same institution. No significant differences were found in age (p = 0.107), body weight (p = 0.051), sex (p = 0.453), clinical stage V (p = 1), substage b (p = 0.573), T-cell phenotype (p = 0.340), overall response (p = 1), and hypercalcaemia status (p = 1) between the LHOP and CHOP groups. The adverse effects of l-asparaginase were well tolerated and self-limiting. The median PFS (progression-free survival) and median ST (survival time) in the LHOP group were 344 days (range: 28-940 days) and 344 days (range: 70-940 days), respectively. The median PFS and median ST in the CHOP group were 234 days (range: 49-1822 days) and 314 days (range: 50-1822 days), respectively. The dogs that received LHOP chemotherapy had a significantly longer PFS than the dogs that received CHOP chemotherapy (p = 0.001). No significant difference was observed in ST between the LHOP and CHOP groups (p = 0.131). Our study findings thus indicate that the LHOP protocol can be used as a first-line chemotherapeutic protocol in canine multicentric lymphoma.

Association between weight change during initial chemotherapy and clinical outcome in dogs with multicentric lymphoma.

The majority of the known prognostic factors in dogs with lymphoma have been evaluated before treatment commences or at the time of diagnosis. Prognostic factors evaluated during the initial phase of treatment are less described but may provide important clinical information. In this retrospective study, 82 canine lymphoma patients were categorized according to the weight change between diagnosis and after 5 weeks of chemotherapy. Dogs that gained greater than 5% or lost greater than 5% of initial body weight were categorized as increased- or decreased-weight groups, respectively. Those in which weight changed less than 5% were categorized as the maintained-weight group. The median progression-free survival (PFS) in the increased-weight group, maintained-weight group and decreased-weight group was 226, 256 and 129 days, respectively. The decreased-weight group had significantly shorter PFS than the increased and maintained groups (P = .023, P = .003, respectively). The median survival time (ST) in the increased-weight group, maintained-weight group and decreased-weight group was 320, 339 and 222 days, respectively. There was no significant difference in ST among the three groups (P = .128). In Cox-regression results, weight change group and initial body weight were significant risk factors associated to PFS (P = .007, P = .001, respectively) while only patient's initial body weight was a significant risk factor to ST (P = .013). In conclusion, evaluation of initial body weight and weight changes over time can provide valuable information regarding PFS and ST in dogs with multicentric lymphoma.

Kynurenine 3-monooxygenase (KMO), and signal transducer and activator of transcription 3 (STAT3) expression is involved in tumour proliferation and predicts poor survival in canine melanoma.

Canine melanoma is a malignant tumour that exhibits aggressive behaviour, and frequently metastasizes to regional lymph nodes and distant sites. Currently, there are no effective treatments or practical prognostic biomarkers for canine melanoma. The enzyme kynurenine 3-monooxygenase (KMO), which plays a central role in the tryptophan metabolism, has previously been identified as the main pathogenic factor in neurodegenerative diseases; however, it has recently been found to be positively associated with tumour malignancy in human hepatocellular carcinoma and canine mammary tumours. Signal transducer and activator of transcription 3 (STAT3) is a well-known oncoprotein contributing to the proliferation, survival, invasiveness and metastasis of a variety of cancers. Although whether STAT3 and KMO collaborate in tumorigenesis needs to be further verified, our previous findings showed that inhibition of KMO activity reduced activation of STAT3. This study investigated the expressions of KMO and STAT3/phosphorylated (pSTAT3) by immunohistochemical analysis in 85 cases of canine melanoma, showing their expression levels were high within highly mitotic melanoma cells. KMO Overexpression was significantly associated with increased STAT3 and pSTAT3 expressions. Melanoma tissues with higher KMO, STAT3 and pSTAT3 protein expressions were correlated with reduced survival rates of the canine patients. Moreover, inhibition of KMO activity in canine melanoma cells resulted in reduced cell viability, in addition to decreased expressions of STAT3 and pSTAT3. Our results indicated the significance of KMO and the potential role of KMO/STAT3 interaction in enhancing tumour development. Additionally, KMO and STAT3/pSTAT3 may be viewed as useful biomarkers for the prediction of prognosis of canine melanoma.

Outcome of Canine Multicentric Lymphoma after Single or Divided Treatment with Cyclophosphamide in Multidrug Chemotherapy.

Cyclophosphamide is commonly used in combination chemotherapy to treat dogs with lymphoma. The metabolite of cyclophosphamide, acrolein, can irritate urinary bladder and cause sterile hemorrhagic cystitis. Dividing the administration of cyclophosphamide across multiple days may reduce the concentration of this metabolite in urinary bladder and reduce the possibility of cystitis. However, the impact of the therapeutic effect of this modification is not evaluated and compared to traditional single maximum-tolerated dose regimen. Seventy-two dogs with multicentric lymphoma received either bolus doses or divided doses of cyclophosphamide were included in this study. The incidence of hemorrhagic cystitis between 2 cyclophosphamide treatment groups was not significantly different (P = .357). There was no statistical difference in progression-free survival and survival time between 2 groups (P = .267 and P = .346). This modification of cyclophosphamide administration did not reduce the side effect of cystitis or affect remission and survival times in lymphoma dogs.

Inhibiting autophagy potentiates the antitumor efficacy of Euphorbia royleana for canine mammary gland tumors.

BACKGROUND: Canine mammary gland tumors (cMGTs) are the most common neoplasms in intact female canines and viewed as a suitable model for studying human breast cancers. Euphorbia royleana has been reported to have a variety of antitumor efficacies. We have prepared the crude extracts of E. royleana in ethanol and hexane solvents to evaluate the anti-tumor effects for cMGT in vitro and in vivo. RESULTS: The results showed that E. royleana could inhibit cell proliferation and colony formation in cMGT cells. The suppression of tumor cell growth resulted from necrosis and cell cycle arrest. Moreover, autophagy appears to play a critical role in E. royleana-mediated cell death by triggering cell apoptosis. The in vivo results also revealed that E. royleana treatment could reduce the size of solid tumors while exhibiting low toxicity in cMGT-bearing nude mice. CONCLUSIONS: The anti-tumor mechanisms of E. royleana were firstly verified to show it would cause autophagic cell death, apoptosis, and cell cycle arrest in canine mammary tumor cells. The in vitro and in vivo findings in the present study revealed E. royleana has potential anticancer effects for the treatment of canine mammary gland tumors.

Elevated plasma YKL-40 level is found in the dogs with cancer and is related to poor prognosis.

YKL-40, a secreted glycoprotein, may serve as an autoantigen, which mediates multiple inflammatory diseases and cancers. A high YKL-40 serum level is correlated with metastasis and poor survival in a variety of human cancers. However, the role of YKL-40 in dogs is still under evaluation. Herein, we examined the associations between plasma YKL-40 level and YKL-40 autoantibody (YAA) titers with malignancy and prognosis in canine cancer. Plasma levels of YKL-40 in healthy dogs (n = 20) and in dogs (n = 82) with cancer were evaluated using enzyme-linked immunosorbent assay. Our results indicated that plasma YKL-40 levels were significantly higher (p < 0.01) in dogs with cancer than in healthy dogs. A significant decrease in the YAA titers was detected in the dogs with cancer when compared with those of the healthy dogs (p < 0.05), although the change was not correlated with the YKL-40 levels. Among the dogs with cancer, plasma YKL-40 levels in the dogs that later relapsed or had metastasis were significantly higher than in the dogs with no signs of relapse (p < 0.01) or metastasis (p < 0.05). The relapse and metastasis rates were significantly higher in the high YKL-40 group (> 180 pg/mL) than in the low YKL-40 group (< 180 pg/mL). The results imply that plasma YKL-40 levels might have the potential to be developed as a marker of malignancy progression and prognosis in canine cancers.

A 3-year surveillance on causes of death or reasons for euthanasia of domesticated dogs in Taiwan.

Over the last 2 decades, there has been growing interest in research on the mortality of domesticated pets. These studies relied on an effective data-collecting system. During 2012-2014, a real-time reporting system was designed for mortality data in owned dogs and cats. The present retrospective study aimed to report on the causes of death (CODs) or reasons for euthanasia (RFEs) in domesticated dogs in Taiwan, and to investigate CODs/RFEs segregated by demographic variables. Data from 2306 domesticated dogs were acquired during the 3-year period in the present study. The median age at death of the study population was 10.2 years (median interquartile range 7.0-14.0; range 0.0-25.0). Crossbred, female, and neutered dogs showed greater ages at death than other groups. The most common COD/RFE was neoplasia, followed by multiple organ involvement (MOI) and cardiovascular diseases. Segregated by cut-off ages, the most common COD/RFE was infection among dogs younger than 3 years or 1year, and neoplasia among dogs at or older than 3 years or 1year of age; the most common COD/RFE was neoplasia among dogs younger than median age, and MOI among dogs at or older than median age. Segregated by geographic variables, the ranking and frequency of CODs/RFEs displayed different patterns between the capital city/non-capital areas, and among areas stratified by human population densities. The study provides various insights into age at death and CODs/RFEs in owned-dog population in Taiwan, and provides new directions for future research.

Granulysin expressed in a humanized mouse model induces apoptotic cell death and suppresses tumorigenicity.

Granulysin (GNLY) is a cytolytic and proinflammatory protein expressed in activated human cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. Conventional mouse models cannot adequately address the triggering mechanism and immunopathological pathways in GNLY-associated diseases due to lack of the GNLY gene in the mouse genome. Therefore, we generated a humanized immune system (HIS) mouse model by transplanting human umbilical cord blood mononuclear cells into NOD.Cg-Prkdcscid Il2rgtm1Wjl /SzJ (NSG) mice after sublethally irradiation. We examined the GNLY expression and its effects on tumor growth using this system. Our HIS mice expressed human CD45+, CD4+, CD8+ and CD56+ cells in the peripheral blood and spleen. A high expression level of human Th1/Th2 and NK cytokines was detected, indicating the activation of both T and NK cells. Importantly, we found an elevated level of GNLY in the serum and it was produced by human CTLs and NK cells obtained from the peripheral blood mononuclear cells and spleen cells in the HIS mice. The serum level of GNLY was negatively correlated with the proliferation of transplanted tumor cells in HIS mice. Collectively, our findings strongly supported that HIS mouse as a valuable model for studying human cancer under an intact immune system and the role of GNLY in tumorigenesis.

A real-time reporting system of causes of death or reasons for euthanasia: A model for monitoring mortality in domesticated cats in Taiwan.

A novel, real-time mortality recording system was designed to collect mortality data in companion animals from veterinary hospitals in Taiwan. This retrospective study aims to introduce the system, and to utilize the data collected for further investigation of the lifespan and mortality of the domesticated cat population stratified by demographic variables. Our data revealed that 1325 domesticated cats were acquired between 2012 and 2014. The median age of the study population was 8.0 years (IQR 3.0-13.0; range 0.0-22.7). Neutered and purebred cats lived longer. The most common causes of death were renal and urologic disorders, followed by neoplasia, infection, cardiovascular disorders, and trauma. Independent factors for common causes were surveyed. Advanced age and neutering was found to be associated with death due to renal and urologic disorders as well as with neoplasia. In contrast, younger age was found to be associated with death due to trauma and infection; being unneutered and living in the capital city were found to be associated with death due to trauma. Being male or purebred was found to be associated with death due to cardiovascular disorders.

Assessment of temporal association of relapse of canine multicentric lymphoma with components of the CHOP protocol: Is cyclophosphamide the weakest link?

Combination chemotherapy, using cyclophosphamide, hydroxydaunorubicin, vincristine and prednisolone (CHOP), is the most commonly used treatment for canine lymphoma. Most affected dogs respond during the initial stages of chemotherapy, but many relapse. The aim of this study was to evaluate the relationship between the use of specific chemotherapy drugs and clinical relapse, using the modified Madison-Wisconsin, 25 week chemotherapy protocol. Forty-one of 68 dogs affected with multicentric lymphoma relapsed during the treatment period. Relapse occurred more frequently after the administration of cyclophosphamide (n = 24; P < 0.01), compared with vincristine (n = 9) or doxorubicin (n = 5). Therefore, the therapeutic outcome of traditional CHOP-based chemotherapy might be improved by replacing cyclophosphamide with other cytotoxic drugs.

Comparison of efficacy and toxicity of doxorubicin and mitoxantrone in combination chemotherapy for canine lymphoma.

Forty-four dogs with multicentric lymphoma were treated using a cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) induction protocol or treated using a cyclophosphamide, mitoxantrone, vincristine, and prednisolone (CMOP) induction protocol. There was no statistical difference in signalment and the presence of historical negative prognostic factors between the groups. The median progression-free survival (PFS) in the CHOP and CMOP groups were 222 d and 162 d, respectively (P = 0.75). The median survival time (MST) of dogs in CHOP and CMOP groups were 318 d and 242 d, respectively (P = 0.63). Anorexia and diarrhea episodes were significantly higher in the CHOP group than in the CMOP group (P = 0.02 and P = 0.01, respectively). These results suggest that the CMOP protocol provides similar PFS, MST and causes fewer side effects compared to the CHOP protocol. Therefore, the CMOP protocol may be another treatment choice for canine multicentric lymphoma.

Comparaison de l'efficacité et de la toxicité de la doxorubicine et du mitoxantrone dans la chimiothérapie combinée pour le lymphome canin. Quarante-quatre chiens atteints d'un lymphome multicentrique ont été traités à l'aide d'un protocole d'induction au cyclophosphamide, à la doxorubicine, à la vincristine et à la prednisolone (CHOP) ou traités en utilisant un protocole d'induction à la cyclophosphamide, au mitoxantrone, à la vincristine et à la prednisolone (CMOP). Il n'y a eu aucune différence statistique dans le signalement et la présence des facteurs de pronostic négatifs historiques entre les groupes. La survie sans progression (SSP) médiane des groupes CHOP et CMOP était de 222 jours et de 162 jours, respectivement (P = 0,75). La durée de survie moyenne (DSM) des chiens des groupes CHOP et CMOP a été de 318 jours et de 242 jours, respectivement (P = 0,63). Les épisodes d'anorexie et de diarrhée ont été significativement plus élevés dans le groupe CHOP comparativement au groupe CMOP (P = 0,02 et P = 0,01, respectivement). Ces résultats suggèrent que le protocole CMOP offre une SSP et une DSM semblables tout en causant moins d'effets secondaires comparativement au protocole CHOP. Par conséquent, le protocole CMOP peut représenter un autre choix de traitement pour les lymphomes multicentriques canins.(Traduit par Isabelle Vallières).

Gene-expression profiling to identify genes related to spontaneous tumor regression in a canine cancer model.

Microarray transcriptome study in cancer has been commonly used to investigate tumorigenic mechanisms. The unique growth pattern of spontaneous regression (SR) after progressive (P) growth in canine transmissible venereal tumor (CTVT) provides a valuable cancer model to study the genome-wide differences in samples between the two stages of growth. In this study, Affymetrix analysis was performed based on the canine genome to compare the gene expression profiles of CTVT P- and SR-phase tumors. A total of 459 (278 up-regulated and 181 down-regulated) genes were identified as being differentially-expressed during the SR phase by the 2-fold method. Further analysis of these genes revealed that the expression of three genes associated with IL-6 production -TIMD-4, GPNMB and PLTP - was significantly higher in SR-phase tumors than in P-phase tumors; these results were also confirmed by real time RT-PCR in tumor tissues of beagles. In addition, we found that Th17-related genes were over-expressed in the SR phase, suggesting autoimmune responses involvement in tumor regression. Although the interaction between CTVT and host immunity were partially investigated in previous studies, our results enable us to gain new insight into the genes and possible mechanisms involved in tumor regression and reveal potentially useful targets for cancer therapy.

Overexpression of chemokine ligand 7 is associated with the progression of canine transmissible venereal tumor.

BACKGROUND: Chemokines play multiple roles in the development and progression in a variety of tumors. Chemokine (C-X-C motif) ligand 7 (CXCL7) has been found associated with pro-inflammatory responses, but its role in cancer growth remains unclear. Our previous study showed that R phase tumor infiltrating lymphocytes (TILs) produced large amounts of interleukin (IL)-6 which antagonized transforming growth factor (TGF)-ß derived from CTVT to diminish the immune-suppressive microenvironment. Now we intend to determine the expression pattern of CXCL7 and the role of IL-6/TGF-ß in CXCL7 induction during spontaneous progressive (P) and regressive (R) phases in canine transmissible venereal tumor (CTVT). RESULTS: We have demonstrated that CXCL7 expressed at high level in P phase and down-regulated in R phase by western blot and real-time PCR. This suggested that CXCL7 expression was negatively correlated with the tumor growth. Co-culturing TILs with CTVT cells was found to reduce CXCL7 expression, while adding IL-6 blocking antibody reversed it. Moreover, in P phase CTVT, while IL-1ß and TGF-ß had no obvious effect on CXCL7 expression, IL-6 was found significantly to reduce CXCL7 expression in a dose-dependent manner. The mRNA expression results of CXCL7 receptor, CXCR2, further confirmed the effects of IL-6 concentration on the CXCL7 expression. CONCLUSION: CXCL7 overexpression might be associated with the progressive growth of CTVT. The results shown here also suggest the role of CXCL7 in cancer development and the potential as the anti-cancer therapeutic target.

Elevated Krüppel-like factor 4 transcription factor in canine mammary carcinoma.

BACKGROUND: Krüppel-like factors (KLFs) are critical regulators of biological and physiological systems and have been extensively studied for their roles in cell proliferation, differentiation and survival in the context of cancer. Among the KLFs, KLF4 is highly expressed in human breast cancers and plays an oncogenic role. The present study examined the expression of KLF4 and assessed its significance in canine mammary carcinoma. RESULTS: Immunohistochemistry was employed to investigate the expression of KLF4 in 142 cases of canine mammary tumor. 75 of the 142 (52.8%) cases were histologically confirmed as mammary carcinoma. Quantification of immunohistochemistry was carried out using Quick score which multiply the staining intensity by the percentage of positive cells. High KLF4 expression was identified in 44 of the 75 (59%) dogs with mammary carcinoma and none in the benign cases. High KLF4 expression occurred only in the tumor cells and not the adjacent normal cells in mammary carcinoma (P < 0.001). Moreover, the high expression level of KLF4 expression was statistically associated with poor grade, late stage, histological subtypes of simple and complex carcinoma, and shorter 24-month survival. The Kaplan-Meier survival analysis also indicated that dogs with high nuclear KLF4 expression had a significantly shorter survival than those with low/moderate KLF4 expression (P = 0.011). CONCLUSIONS: KLF4 is highly and frequently expressed in canine mammary carcinoma and correlates with a more aggressive phenotype.

A 12-year retrospective study of canine testicular tumors.

To provide up-to-date information on the incidence and risk factors of canine testicular tumors, 476 pathological reports of male canine tumors from two institutes of veterinary medicine in Taiwan over a period of 12 years were reviewed. The detection rate of testicular tumors was 16.8% (80/476) in male canine tumors, and 94.1% (80/85) in male genital tumors. Ninety-six testicular tumors from 80 dogs were identified in this study, including 33 (34.4%) seminomas (SEMs), 25 (26%) interstitial cell tumors (ICTs), 22 (22.9%) mixed germ cell-stromal cell tumors (MGCSCTs), and 16 (16.6%) Sertoli cell tumors (SCTs). Of the 96 testicular tumors, 52 (54.2%) tumors developed from cryptorchid testes in 45 dogs (56.3%), and 44 (45.8%) tumors developed from scrotal testes in 35 dogs (44.7%). Cryptorchidism was significantly associated with development of MGCSCTs, SCTs, and SEMs, but not ICTs (p<0.01). The detection rate of testicular tumors in the dog younger than 10-years-old was significantly associated with cryptorchidism (p<0.01). Except for mixed breed dogs, the Maltese breed had high detection rate of testicular tumors, and may have high risk in cryptorchidism in this study. In conclusion, our results indicate that cryptorchidism alone or in addition to age will significantly affect the incidence and type of canine testicular tumors, and a high detection rate of testicular tumors in Maltese dogs is documented for the first time.