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12 pages, 4598 KiB

Open AccessArticle

The High Expression of Legumain in Canine Neoplasms: A Retrospective Analysis of 100 Cases

by Chiao-Hsu Ke, Ka-Mei Sio, Shang-Lin Wang, Ying Kuo, Wei-Hsiang Huang and Chen-Si Lin

Animals 2022, 12(4), 504; https://doi.org/10.3390/ani12040504 - 17 Feb 2022

Cited by 3 | Viewed by 1971

Legumain, a novel asparaginyl endopeptidase, has been observed to be overexpressed in several types of human solid tumors. Elevated levels of legumain are found in human cancers, and this oncoprotein may facilitate tumor invasion and metastasis when overexpressed. These findings suggest that legumain [...] Read more.

Legumain, a novel asparaginyl endopeptidase, has been observed to be overexpressed in several types of human solid tumors. Elevated levels of legumain are found in human cancers, and this oncoprotein may facilitate tumor invasion and metastasis when overexpressed. These findings suggest that legumain plays a malignant role in cancer biology. However, currently, no publications have identified the role of legumain in the development of canine cancers. The present study first compared the expression patterns of legumain in paraffin-embedded canine tumor tissues, with those of normal tissues, by immunohistochemistry. A total of 100 canine tumor samples, including mast cell tumors, soft tissue sarcoma, hemangiosarcoma, lymphoma, mammary gland carcinoma, hepatoid gland tumor, squamous cell carcinoma, trichoblastoma, and melanoma were evaluated. Compared with the normal tissues, all tumor samples displayed high intensities of legumain expression. Mesenchymal-type tumors displayed immunoreactivity for legumain, with an average expression of 40.07% ± 1.70%, which was significantly lower than those of epithelial tumors and other types of tumors, which had median expressions of 49.12% ± 1.75% and 47.35% ± 2.71%, respectively (p < 0.05). These findings indicate that legumain has a high potential to be a candidate for distinguishing tumors from normal tissues. Although further studies on a larger number of cases are necessary to clarify the clinical application of legumain, the overexpression patterns of legumain in canine tumor tissues are reported, for the first time, in this study. Full article

(This article belongs to the Special Issue Canine and Feline Tumors: Research Advances and Diagnostic Innovations)

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13 pages, 3248 KiB

Open AccessArticle

Metabolic Flexibility in Canine Mammary Tumors: Implications of the Carnitine System

by Nunzio Antonio Cacciola, Mariafrancesca Sgadari, Fabrizia Sepe, Orsolina Petillo, Sabrina Margarucci, Manuela Martano, Paola Maiolino and Brunella Restucci

Animals 2021, 11(10), 2969; https://doi.org/10.3390/ani11102969 - 15 Oct 2021

Cited by 5 | Viewed by 1906

Abstract

Deregulation of fatty acid catabolism provides an alternative energy source to glycolysis for cancer cell survival and proliferation. The regulator enzymes of the carnitine system (CS), responsible for the transport of fatty acids across mitochondrial membranes for

β

-oxidation are deregulated in tumorigenesis. [...] Read more.

Deregulation of fatty acid catabolism provides an alternative energy source to glycolysis for cancer cell survival and proliferation. The regulator enzymes of the carnitine system (CS), responsible for the transport of fatty acids across mitochondrial membranes for

β

-oxidation are deregulated in tumorigenesis. Recently, we found that Carnitine Palmitoyl Transferase 1 (CPT1), a crucial regulator of CS components, is expressed and dysregulated in canine mammary tumor (CMT) tissues and cells. In this study, we examined the protein expression of the three remaining enzymes of CS (Carnitine Acylcarnitine Translocase (CACT), Carnitine Palmitoyl Transferase 2 (CPT2), Carnitine O-acetyltransferase (CrAT), in canine mammary cells and tissues by Western blot and immunohistochemistry. Protein expression of the components of CS was found in normal mammary glands and a concomitant deregulation of expression in CMT tissues that inversely correlated with the degree of tumor differentiation. Moreover, the expression and a different deregulation of CS-related proteins was also observed in CF33, CMT-U27, CMT-U309, and P114 cell lines used as in vitro model. These results demonstrate for the first time the expression of CS components in CMT tissues and cancer cells; however, further studies are needed to elucidate their roles in dogs as well. Full article

(This article belongs to the Special Issue Canine and Feline Tumors: Research Advances and Diagnostic Innovations)

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16 pages, 4466 KiB

Open AccessArticle

Immunoexpression of Trefoil Factor 1 in Non-Neoplastic and Neoplastic Canine Gastric Tissues

by Ana R. Flores, Marisa Castro, Alexandra Rêma, João R. Mesquita, Marian Taulescu, Fátima Gärtner, Fernanda Seixas and Irina Amorim

Animals 2021, 11(10), 2855; https://doi.org/10.3390/ani11102855 - 29 Sep 2021

Cited by 1 | Viewed by 1598

Abstract

TFF1 expression is markedly reduced in human GCs, suggesting that TFF1 is a tumor suppressor for human gastric cancer. The present study evaluated the expression and distribution pattern of TFF1 in paraffin-embedded canine gastric tissue samples, including normal mucosa (n = 3), polyps [...] Read more.

TFF1 expression is markedly reduced in human GCs, suggesting that TFF1 is a tumor suppressor for human gastric cancer. The present study evaluated the expression and distribution pattern of TFF1 in paraffin-embedded canine gastric tissue samples, including normal mucosa (n = 3), polyps (n = 8), carcinomas (n = 31) and their adjacent non-neoplastic mucosa (n = 30), neoplastic emboli (n = 14), and metastatic lesions (n = 9), by immunohistochemistry (IHC). All normal gastric tissues expressed TFF1 in the superficial foveolar epithelium and mucopeptic cells of the neck region. Most gastric polyps (GPs) displayed immunoreactivity for TFF1 in >75% of the epithelial component. In GCs, the expression of TFF1 was found reduced in 74.2% of the cases. The level of TFF1 expression had a decreased tendency from normal gastric mucosa to GPs and GCs (p < 0.05). No significant differences in the expression of TFF1 were found in GCs, according to age, sex, histological type based on World Health Organization (WHO) and Lauren classification, tumor location, depth of tumor invasion, presence of neoplastic emboli or metastatic lesions. The median survival time of GC patients with preserved and reduced TFF1 immunoexpression were 30 and 12 days, respectively. Kaplan–Meier analysis revealed no significant survival differences between the two groups (p > 0.05). These findings suggest that TFF1 protein may play a role in canine gastric carcinogenesis, and further studies are necessary to define its usefulness as a prognostic indicator in canine gastric carcinoma. Full article

(This article belongs to the Special Issue Canine and Feline Tumors: Research Advances and Diagnostic Innovations)

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12 pages, 1426 KiB

Open AccessArticle

Evaluation of the Safety and Feasibility of Apheresis in Dogs: For Application in Metastatic Cancer Research

by Haru Yamamoto, Mohamed Elbadawy, Koudai Fujisaka, Yomogi Sato, Takahiro Ohmori, Yuta Shinohara, Yui Hatano, Daichi Kobayashi, Ayana Gomyo, Yuji Sudo, Daigo Azakami, Tsuyoshi Uchide, Ryuji Fukushima, Shohei Morita, Amira Abugomaa, Hideyuki Yamawaki, Masahiro Kaneda, Tatsuya Usui and Kazuaki Sasaki

Animals 2021, 11(10), 2770; https://doi.org/10.3390/ani11102770 - 23 Sep 2021

Cited by 1 | Viewed by 2427

Abstract

In patients with solid tumors, circulating tumor cells (CTCs) spread in their blood and function as a seed for metastases. However, the study of CTCs has been limited by their rarity, low frequency, and heterogeneity. The efficient collection of CTCs will contribute to [...] Read more.

In patients with solid tumors, circulating tumor cells (CTCs) spread in their blood and function as a seed for metastases. However, the study of CTCs has been limited by their rarity, low frequency, and heterogeneity. The efficient collection of CTCs will contribute to further research of metastatic cancers. Apheresis is a process in which the whole blood of an individual is passed through a machine that isolates a particular constituent and returns the remainder to the circulation. In the present study, we investigated the safety and feasibility of apheresis to separate peripheral blood monocytes (PBMCs), whose density is closely similar to that of CTCs, and to capture intravenously administered human breast cancer cells, MCF7s, from the dogs. No life-threatening events were observed in dogs during the apheresis process. The changes in the hemogram were transient and recovered gradually within a few days after apheresis. During apheresis, 50 mL of PBMCs could be collected from each dog. Notably, a thrombus was formed along the circuit wall during apheresis, which decreased the blood collection pressure. MCF7 cells were successfully captured by the apheresis machine. The captured cells were regrown in vitro and characterized compared with the original cells. In conclusion, apheresis could be safely performed in dogs to isolate CTCs with precautions to maintain hemodynamic stability. Full article

(This article belongs to the Special Issue Canine and Feline Tumors: Research Advances and Diagnostic Innovations)

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15 pages, 4226 KiB

Open AccessArticle

Investigation of Prognostic Value of Claudin-5, PSMA, and Ki67 Expression in Canine Splenic Hemangiosarcoma

by Juliana Moreira Rozolen, Tamires Goneli Wichert Teodoro, Renata Afonso Sobral, Felipe Augusto Ruiz Sueiro, Renee Laufer-Amorim, Fabiana Elias and Carlos Eduardo Fonseca-Alves

Animals 2021, 11(8), 2406; https://doi.org/10.3390/ani11082406 - 14 Aug 2021

Cited by 8 | Viewed by 3039

Abstract

Splenic hemangiosarcoma (HSA) is a malignant tumor of endothelial cells that affects middle-aged and elderly dogs and is characterized by the formation of new blood vessels, commonly associated with necrotic and hemorrhagic areas. Despite its importance in veterinary medicine, few studies have identified [...] Read more.

Splenic hemangiosarcoma (HSA) is a malignant tumor of endothelial cells that affects middle-aged and elderly dogs and is characterized by the formation of new blood vessels, commonly associated with necrotic and hemorrhagic areas. Despite its importance in veterinary medicine, few studies have identified markers with prognostic value for canine HSA. Thus, this study aimed to associate the clinicopathological findings (prostate-specific membrane antigen [PSMA], Claudin-5, and Ki67 gene and protein expression) with overall survival in HSA-affected patients. Fifty-three formalin-fixed and paraffin-embedded canine splenic HSA samples, previously diagnosed by histopathological examination, were used in this study. Claudin-5, PSMA, and Ki67 protein expression levels were evaluated by immunohistochemistry, and gene expression was evaluated by quantitative polymerase chain reaction. Claudin-5 protein overexpression was observed in patients with metastasis (p = 0.0078) and with stage III tumors compared to those with stage I and II tumors (p = 0.0451). In patients treated with surgery alone, low PSMA gene and protein expression (p = 0.05 and p = 0.0355, respectively) were associated with longer survival time. Longer survival time was observed in patients with a low Ki67 index (p = 0.0488). Our results indicate that Claudin-5 protein expression is associated with metastatic status, and PSMA gene and protein expression, and Ki67 index are associated with survival time. Full article

(This article belongs to the Special Issue Canine and Feline Tumors: Research Advances and Diagnostic Innovations)

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10 pages, 1858 KiB

Open AccessEditor’s ChoiceArticle

High Drug Resistance in Feline Mammary Carcinoma Cell Line (FMCm) and Comparison with Human Breast Cancer Cell Line (MCF-7)

by Ana Salomé Correia, Rita Matos, Fátima Gärtner, Irina Amorim and Nuno Vale

Animals 2021, 11(8), 2321; https://doi.org/10.3390/ani11082321 - 6 Aug 2021

Viewed by 3389

Abstract

Drug repurposing and drug combination are important therapeutic approaches in cancer therapy. Drug repurposing aims to give new indications to drugs, rather than the original indication, whereas drug combination presupposes that the effect that is obtained should be more beneficial than the effect [...] Read more.

Drug repurposing and drug combination are important therapeutic approaches in cancer therapy. Drug repurposing aims to give new indications to drugs, rather than the original indication, whereas drug combination presupposes that the effect that is obtained should be more beneficial than the effect obtained by the individual drugs. Previously, drug repurposing and the combination of different drugs was evaluated in our research group against human breast cancer cells (MCF-7 cells). Our results demonstrated that the response obtained through the combination of drugs, when compared with the single drugs, led to more synergic responses. Therefore, using potential drugs for repurposing, combined with a reference drug in breast cancer (5-Fluorouracil), was the major aim of this project, but for the first time using the feline mammary carcinoma cell line, FMCm. Surprisingly, the feline neoplastic cells demonstrated considerable resistance to the drugs tested in isolation, and the combination was not effective, which contrasted with the obtained MCF-7 cells’ response. Full article

(This article belongs to the Special Issue Canine and Feline Tumors: Research Advances and Diagnostic Innovations)

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10 pages, 533 KiB

Open AccessArticle

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

by Jih-Jong Lee, Albert Taiching Liao and Shang-Lin Wang

Animals 2021, 11(8), 2199; https://doi.org/10.3390/ani11082199 - 26 Jul 2021

Cited by 4 | Viewed by 5687

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Canine and Feline Tumors: Research Advances and Diagnostic Innovations)

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13 pages, 3188 KiB

Open AccessArticle

Overexpression of Mucin 1 Suppresses the Therapeutical Efficacy of Disulfiram against Canine Mammary Tumor

by Ying Zhao, Zixiang Lin, Zhaoyan Lin, Chaoyu Zhou, Gang Liu, Jiahao Lin, Di Zhang and Degui Lin

Animals 2021, 11(1), 37; https://doi.org/10.3390/ani11010037 - 27 Dec 2020

Cited by 5 | Viewed by 2442

Abstract

Mucin 1 (MUC1), a transmembrane protein, is closely associated with the malignancy and metastasis of canine mammary tumors; however, the role of overexpressed MUC1 in the development of cancer cells and response to drug treatment remains unclear. To address this question, we developed [...] Read more.

Mucin 1 (MUC1), a transmembrane protein, is closely associated with the malignancy and metastasis of canine mammary tumors; however, the role of overexpressed MUC1 in the development of cancer cells and response to drug treatment remains unclear. To address this question, we developed a new canine mammary tumor cell line, CIPp-MUC1, with an elevated expression level of MUC1. In vitro studies showed that CIPp-MUC1 cells are superior in proliferation and migration than wild-type control, which was associated with the upregulation of PI3K, p-Akt, mTOR, Bcl-2. In addition, overexpression of MUC1 in CIPp-MUC1 cells inhibited the suppressing activity of disulfiram on the growth and metastasis of tumor cells, as well as inhibiting the pro-apoptotic effect of disulfiram. In vivo studies, on the other side, showed more rapid tumor growth and stronger resistance to disulfiram treatment in CIPp-MUC1 xenograft mice than in wild-type control. In conclusion, our study demonstrated the importance of MUC1 in affecting the therapeutical efficiency of disulfiram against canine mammary tumors, indicating that the expression level of MUC1 should be considered for clinical use of disulfiram or other drugs targeting PI3K/Akt pathway. Full article

(This article belongs to the Special Issue Canine and Feline Tumors: Research Advances and Diagnostic Innovations)

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