C6 Ceramide Inhibits Canine Mammary Cancer Growth and Metastasis by Targeting EGR3 through JAK1/STAT3 Signaling.

Cancer is the leading cause of death in both humans and companion animals. Canine mammary tumor is an important disease with a high incidence and metastasis rate, and its poor prognosis remains a serious clinical challenge. C6 ceramide is a short-chain sphingolipid metabolite with powerful potential as a tumor suppressor. However, the specific impact of C6 ceramide on canine mammary cancer remains unclear. However, the effects of C6 ceramide in canine mammary cancer are still unclear. Therefore, we investigated the role of C6 ceramide in the progress of canine mammary cancer and explored its potential mechanism. C6 ceramide inhibited cell growth by regulating the cell cycle without involving apoptosis. Additionally, C6 ceramide inhibited the migration and invasion of CHMp cells. In vivo, C6 ceramide decreased tumor growth and metastasis in the lungs without side effects. Further investigation found that the knockdown of EGR3 expression led to a noticeable increase in proliferation and migration by upregulating the expressions of pJAK1 and pSTAT3, thus activating the JAK1/STAT3 signaling pathway. In conclusion, C6 ceramide inhibits canine mammary cancer growth and metastasis by targeting EGR3 through the regulation of the JAK1/STAT3 signaling pathway. This study implicates the mechanisms underlying the anti-tumor activity of C6 ceramide and demonstrates the potential of EGR3 as a novel target for treating canine mammary cancer.

Long Non-Coding RNA as a Potential Biomarker for Canine Tumors.

Cancer is the leading cause of death in both humans and companion animals. Long non-coding RNA (lncRNA) plays a crucial role in the progression of various types of cancers in humans, involving tumor proliferation, metastasis, angiogenesis, and signaling pathways, and acts as a potential biomarker for diagnosis and targeted treatment. However, research on lncRNAs related to canine tumors is in an early stage. Dogs have long been considered a promising natural model for human disease. This article summarizes the molecular function of lncRNAs as novel biomarkers in various types of canine tumors, providing new insights into canine tumor diagnosis and treatment. Further research on the function and mechanism of lncRNAs is needed, which will benefit both human and veterinary medicine.

An investigation of the perceptions of laboratory animal welfare issues among undergraduate and graduate veterinary students in southeastern China.

Animal experiments have played a significant role in advancing scientific knowledge and enhancing people's quality of life. In order to better understand the opinions and knowledge of veterinary students in the domain of laboratory animal welfare and to explore and advance the teaching methods used in animal ethics education, a questionnaire was designed and used to conduct a survey among undergraduate and postgraduate students majoring in veterinary medicine. The survey encompassed various topics, such as students' level of knowledge about animal welfare, their perspectives on laboratory animals, their proficiency with animal experiments, and their opinions on teaching methods and content. The respondents were a total of 150 undergraduate students and 148 graduate students. The survey results indicated that most students expressed a strong sense of responsibility for the safeguarding of the welfare of experimental animals. However, there were a few students who lacked compassion for animals. Additionally, there was a general lack of basic theoretical knowledge of animal ethics and an inadequate grasp of experimental techniques among current students. Furthermore, most of the participants expressed a strong sense of responsibility to advocate for animal welfare. Although a substantial number of students were unaware of the existence of agencies for the supervision of work involving laboratory animals, they supported teaching and supervision in the domain of animal welfare and were open to various teaching methods and topics of content. In conclusion, targeted training and education regarding laboratory animal welfare and ethics should be conducted in the future to address the specific needs of students. This study provides a foundation for future animal welfare education and will help to improve the professional skills and humanistic qualities of veterinary students.

Establishment of stable expression of firefly luciferase and EGFP in a canine inflammatory mammary carcinoma cell line and tumor-bearing model in nude mice.

Canine inflammatory mammary carcinoma (CIMC) is a type of canine malignant mammary tumor with a poor prognosis and high mortality. We transduced firefly luciferase and enhanced green fluorescent protein (EGFP) into CHMp, a CIMC cell line, and established CHMp-Luc-EGFP cells. We investigated the characteristics of this cell line in vitro and in vivo. CHMp-Luc-EGFP was passaged continuously 75 times, with stable expression of luciferase and EGFP. Compared with the wild-type, CHMp-Luc-EGFP had similar proliferation, metastasis, histopathology characteristics, and expression of E-cadherin, N-cadherin, and Ki-67. A tumor-bearing model was established by implantation of CHMp-Luc-EGFP cells, and the dynamic changes of tumors were visualized and quantified using the IVIS imaging system. In summary, the cell line we established could reflect the biological characteristics of CHMp cells, visualize the tumor progression in vivo, and provide a powerful tool for the study of CIMC.

Lamellar Keratoplasty Using Acellular Bioengineering Cornea (BioCorneaVetTM) for the Treatment of Feline Corneal Sequestrum: A Retrospective Study of 62 Eyes (2018-2021).

To retrospectively evaluate the effectiveness and outcome of lamellar keratoplasty using acellular bioengineering cornea (BioCorneaVetTM) for the treatment of feline corneal sequestrum (FCS). The medical records of cats diagnosed with FCS that underwent lamellar keratoplasty with BioCorneaVetTM between 2018 and 2021 with a minimum of 3 months of follow-up were reviewed. Follow-up examinations were performed weekly for 3 months, and then optical coherence tomography (OCT) examination was performed on select patients at 0, 3, 6, and 12 months post-operatively. A total of 61 cats (30 left eyes and 32 right eyes) were included. The Persian breed was overrepresented, 48/61 (78.69%). Four different thicknesses of acellular bioengineering cornea were used (200, 300, 400, or 450 microns), and the mean graft size was 8.23 mm (range, 5.00-12.00 mm). Minor complications were composed of partial dehiscence, and protrusion of the graft occurred in 7/62 eyes (11.29%). The median postoperative follow-up was 12.00 months (range, 3-41 months). A good visual outcome was achieved in 60/62 eyes (96.77%), and a mild to moderate corneal opacification occurred in 2/62 (3.23%). No recurrence of corneal sequestrum was observed. From the results, lamellar keratoplasty using acellular bioengineering cornea (BioCorneaVetTM) is an effective treatment for FCS, providing a good tectonic support and natural collagen framework, and resulting in satisfactory visual and cosmetic effects.

Benzyl Isothiocyanate Induces Apoptosis and Inhibits Tumor Growth in Canine Mammary Carcinoma via Downregulation of the Cyclin B1/Cdk1 Pathway.

Background: Canine mammary carcinoma is common in female dogs, and its poor prognosis remains a serious clinical challenge, especially in developing countries. Benzyl isothiocyanate (BITC) has attracted great interest because of its inhibitory effect against tumor activity. However, its effect and the underlying mechanisms of action in canine mammary cancer are not well-understood. Here, we show that BITC suppresses mammary tumor growth, both in vivo and in vitro, and reveal some of the potential mechanisms involved. Methods: The effect of BITC on canine mammary cancer was evaluated on CIPp and CMT-7364, canine mammary carcinoma lines. The cell lines were treated with BITC and then subjected to wound healing and invasion assays. Cell cycles and apoptosis were measured using flow cytometry; TUNEL assay; immunohistochemistry (IHC) for caspase 3, caspase 9, and cyclin D1; hematoxylin and eosin (H&E) staining; and/or quantitative polymerase chain reaction (qPCR). Results: BITC showed a strong suppressive effect in both CIPp and CMT-7364 cells by inhibiting cell growth in vitro; these effects were both dose- and time-dependent. BITC also inhibited migration and invasion of CIPp and CMT-7364 cells. BITC induced G2 arrest and apoptosis, decreasing tumor growth in nude mice by downregulation of cyclin B1 and Cdk1 expression. Conclusion: BITC suppressed both invasion and migration of CIPp and CMT-7364 cells and induced apoptosis. BITC inhibited canine mammary tumor growth by suppressing cyclinB1 and Cdk1 expression in nude mice.

Ivermectin inhibits canine mammary tumor growth by regulating cell cycle progression and WNT signaling.

BACKGROUND: Mammary gland tumor is the most common spontaneous tumor in intact female dogs, and its poor prognosis remains a clinical challenge. Ivermectin, a well-known anti-parasitic agent, has been implicated as a potential anticancer agent in various types of human cancer. However, there are no reports evaluating the antitumor effects of ivermectin in canine mammary tumor. Here, we investigated whether ivermectin was able to inhibit canine mammary tumor development and explored the related mechanisms. RESULTS: Ivermectin inhibited the growth of canine mammary tumor cell lines in a dose- and time-dependent manner. The antitumor effects induced by ivermectin were associated with cell cycle arrest at G1 phase via down-regulation of CDK4 and cyclin D1 expression, with no significant induction of apoptosis. Furthermore, significantly reduced ß-catenin nuclear translocation was observed after treatment with ivermectin, resulting in the inactivation of WNT signaling. Consistent with the results in vitro, a significant suppression of tumor growth by ivermectin was observed in canine mammary tumor xenografts. CONCLUSION: Ivermectin, as a promising anti-cancer agent, inhibits the growth of canine mammary tumor by regulating cell cycle progression and WNT signaling.

Overexpression of matrix metalloproteinase-9 in breast cancer cell lines remarkably increases the cell malignancy largely via activation of transforming growth factor beta/SMAD signalling.

OBJECTIVES: Matrix metalloproteinase 9 (MMP-9) has been frequently noticed in the breast cancers. In this study, we aim to investigate the associations of MMP-9 with the activation of transforming growth factor beta (TGF-ß)/SMAD signalling and the malignancy of breast malignant tumour cells. MATERIALS AND METHODS: The distributions of MMP-9 and TGF-ß in the tissues of canine breast cancers were screened by immunohistochemical assays. A recombinant plasmid expressing mouse MMP-9 was generated and transiently transfected into three different breast cancer cell lines. Cell Counting Kit-8 and colony formation assay were used to study cell viability. Migration and invasion ability were analysed by wound assay and transwell filters. Western blot and quantitative real-time PCR were used to determine the protein and mRNA expression. RESULT: Remarkable strong MMP-9 and TGF-ß signals were observed in the malignant tissues of canine breast cancers. In the cultured three cell lines receiving recombinant plasmid expressing mouse MMP-9, the cell malignancy was markedly increased, including the cell colony formation, migration and epithelial-mesenchymal transition. The levels of activated TGF-ß, as well as SMAD4, SMAD2/3 and phosphorylation of SMAD2, were increased, reflecting an activation of TGF-ß/SMAD signalling. We also demonstrated that the inhibitors specific for MMP-9 and TGF-ß sufficiently blocked the overexpressing MMP-9 induced the activation of SMAD signalling and enhancement on invasion in the tested breast cancer cell lines. CONCLUSION: Overexpression of MMP-9 increases the malignancy of breast cancer cell lines, largely via activation of the TGF-ß/SMAD signalling.

Proteus mirabilis inhibits cancer growth and pulmonary metastasis in a mouse breast cancer model.

A variety of bacteria have been used as agents and vectors for antineoplastic therapy. A series of mechanisms, including native bacterial toxicity, sensitization of the immune system and competition for nutrients, may contribute to antitumor effects. However, the antitumor effects of Proteus species have been minimally studied, and it is not clear if bacteria can alter tumor hypoxia as a component of their antineoplastic effect. In the present study, Proteus mirabilis bacteria were evaluated for the ability to proliferate and accumulate in murine tumors after intravenous injection. To further investigate the efficacy and safety of bacterial injection, mice bearing 4T1 tumors were treated with an intravenous dose of 5×107 CFU Proteus mirabilis bacteria via the tail vein weekly for three treatments. Histopathology, immunohistochemistry (IHC) and western analysis were then performed on excised tumors. The results suggested Proteus mirabilis localized preferentially to tumor tissues and remarkably suppressed the growth of primary breast cancer and pulmonary metastasis in murine 4T1 models. Results showed that the expression of NKp46 and CD11c was significantly increased after bacteria treatment. Furthermore, tumor expression of carbonic anhydrase IX (CA IX) and hypoxia inducible factor-1a (HIF-1a), surrogates for hypoxia, was significantly lower in the treated group than the control group mice as assessed by IHC and western analysis. These findings demonstrated that Proteus mirabilis may a promising bacterial strain for used against primary tumor growth and pulmonary metastasis, and the immune system and reduction of tumor hypoxia may contribute to the antineoplastic and antimetastatic effects observed.

Behavioral and cardiopulmonary effects of dexmedetomidine-midazolam and dexmedetomidine-midazolam-butorphanol in the silver fox (Vulpes vulpes).

OBJECTIVE: To evaluate the behavior and some cardiopulmonary variables of dexmedetomidine-midazolam or dexmedetomidine-midazolam-butor-phanol in the silver fox (Vulpes vulpes). STUDY DESIGN: Blinded, randomized design. ANIMALS: Sixteen adult silver foxes, aged 7-9 months, weighting 6.0-9.2 kg. METHODS: Animals were randomly assigned to dexmedetomidine (50 µg kg-1) and midazolam (0.45 mg kg-1) (group DM) or to dexmedetomidine (30 µg kg-1), midazolam (0.45 mg kg-1) and butorphanol (0.25 mg kg-1) (group DMB), administered intramuscularly. Pulse rate (PR), respiratory rate (fR), noninvasive arterial pressures, oxygen saturation (SpO2), rectal temperature (T) and behavioral scores (posture, sedation, antinociception, jaw relaxation and auditory response) were measured at 5, 10, 20, 30, 40, 50 and 60 minutes after injection. Time from drug injection to recumbency with no response to stimuli (IT) and time from administration of atipamezole (0.2 mg kg-1) to standing with coordination (RT) were recorded. The occurrences of adverse events were recorded. Data were analyzed by two-tailed unpaired t-tests and Bonferroni post hoc tests. Significant differences were accepted at p<0.05. RESULTS: There were no statistically significant differences between the groups for IT or RT. Arterial pressures were higher in DMB at each time point except at 5 minutes. PR was lower in DM at each time point except at 10 and 60 minutes. No significant difference was found between the groups for fR, SpO2 and T. The behavioral scores were significantly lower (lower quality immobilization) in DMB at 5,10 and 60 minutes. CONCLUSIONS AND CLINICAL RELEVANCE: IT and RT were not different between the groups. Both protocols provided immobilization for 30-40 minutes with excellent muscle relaxation and analgesia adequate for clinical examinations and some simple surgical procedures.

Comparison of the effects of propofol and emulsified isoflurane alone or combined with dexmedetomidine on induction of anesthesia in dogs.

OBJECTIVE: To compare the respective effects of propofol and emulsified isoflurane administered alone and in combination with dexmedetomidine on the quality of induction of anesthesia, physiological variables and recovery in dogs. STUDY DESIGN: Prospective, randomized, experimental trial. ANIMALS: Thirty-six adult mixed-breed dogs. METHODS: Animals were randomly assigned to one of four induction protocols: propofol alone (group P); emulsified isoflurane alone (group EI); both propofol and dexmedetomidine (group PD), or both emulsified isoflurane and dexmedetomidine (group EID). Pulse rate (PR), respiratory rate (fR ), non-invasive arterial blood pressure and arterial blood gases were measured at baseline, before induction, immediately after intubation (time 0), and at 5 minute intervals until the dog began to swallow and the trachea was extubated. The quality of induction and recovery, and degree of ataxia were scored by a single investigator unaware of group assignment. The durations of anesthesia and recovery, and the incidence of adverse events were recorded. RESULTS: There were no clinically significant differences among the groups in induction quality. Systolic arterial pressure was lower in EID compared with P at 5 minutes. PR and fR were lower in PD and EID compared with P after induction. The PaCO2 at 5 minutes was higher than at baseline in group P. Ataxia score was lower in EID than in P. Time from induction to extubation and time from extubation to sternal recumbency were lower in EID compared with PD. CONCLUSIONS AND CLINICAL RELEVANCE: There were no clinically significant differences among the groups in induction quality. In PD and EID, but not in P, PR and fR were decreased after induction. The EID combination resulted in smooth and rapid induction and recovery and thus may be useful clinically for induction of anesthesia.