Plasma matrix metalloproteinase‐9 activity in cats with lymphoma

Tamamoto, Takashi; Ohno, Koichi; Takahashi, Masashi; Fukushima, Kenjiro; Kanemoto, Hideyuki; Fujino, Yasuhito; Tsujimoto, Hajime

doi:10.1111/vco.12097

Cited by 5 publications

(4 citation statements)

References 14 publications

(20 reference statements)

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“…A recent review article describes that MMPs are present in a variety of animals, including cats [ 38 ]. For example, studies have shown that MMPs are expressed in feline tumors, including MMP9 and MMP2, in feline meningioma and mammary cancer [ 39 , 40 ], and MMP9 in feline lymphoma [ 41 ]. Therefore, it is not surprising that the CD147, as an inducer of MMP activity, would have a role in feline tumors as it does for human cancer.…”

Section: Discussionmentioning

confidence: 99%

CD147 and Cyclooxygenase Expression in Feline Oral Squamous Cell Carcinoma

Nasry

Wang

Jones

et al. 2018

Veterinary Sciences

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Feline oral squamous cell carcinoma (OSCC) is a highly invasive form of cancer in cats. In human OSCC, cluster of differentiation 147 (CD147) contributes to inflammation and tumor invasiveness. CD147 is a potential therapeutic target, but the expression of CD147 in feline OSCC has not been examined. Immunohistochemistry was used to determine if cyclooxygenase 2 (COX-2) and CD147 expression in feline OSCC biopsies was coordinated. Tumor cells were more likely to express COX-2 (22/43 cases or 51%) compared to stroma (8/43 or 19%) and adjacent oral epithelium (9/31 cases or 29%) (p < 0.05). CD147 was also more likely to occur in tumor cells compared to stroma and adjacent mucosa, with 21/43 (49%) of cases having >50% tumor cells with mild or moderate CD147 expression, compared to 9/28 (32%) in adjacent epithelium and only 5/43 (12%) in adjacent stroma (p < 0.05). In feline OSCC cell lines (SCCF1, SCCF2, and SCCF3), CD147 gene expression was more consistently expressed compared to COX-2, which was 60-fold higher in SCCF2 cells compared to SCCF1 cells (p < 0.05). CD147 expression did not correlate with COX-2 expression and prostaglandin E2 (PGE2) secretion, indicating that they may be independently regulated. CD147 potentially represents a novel therapeutic target for the treatment of feline OSCC and further study of CD147 is warranted.

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Section: Discussionmentioning

confidence: 99%

CD147 and Cyclooxygenase Expression in Feline Oral Squamous Cell Carcinoma

Nasry

Wang

Jones

et al. 2018

Veterinary Sciences

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“…To determine our enrolment target, exact, single-stage, phase II sample size tables were used ( 36 ). A target activity or a response rate of 35% was chosen as the low end of accepted response rates in treatment protocols used for refractory or resistant canine lymphoma ( 37 – 41 ). P 0 was chosen as 5% as a purposefully low threshold, given the preliminary nature of this investigation.…”

Section: Methodsmentioning

confidence: 99%

Metabolic Abnormalities Detected in Phase II Evaluation of Doxycycline in Dogs with Multicentric B-Cell Lymphoma

et al. 2018

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Doxycycline has antiproliferative effects in human lymphoma cells and in murine xenografts. We hypothesized that doxycycline would decrease canine lymphoma cell viability and prospectively evaluated its clinical tolerability in client-owned dogs with spontaneous, nodal, multicentric, substage a, B-cell lymphoma, not previously treated with chemotherapy. Treatment duration ranged from 1 to 8 weeks (median and mean, 3 weeks). Dogs were treated with either 10 (n = 6) or 7.5 (n = 7) mg/kg by mouth twice daily. One dog had a stable disease for 6 weeks. No complete or partial tumor responses were observed. Five dogs developed grade 3 and/or 4 metabolic abnormalities suggestive of hepatopathy with elevations in bilirubin, ALT, ALP, and/or AST. To evaluate the absorption of oral doxycycline in our study population, serum concentrations in 10 treated dogs were determined using liquid chromatography tandem mass spectrometry. Serum levels were variable and ranged from 3.6 to 16.6 µg/ml (median, 7.6 µg/ml; mean, 8.8 µg/ml). To evaluate the effect of doxycycline on canine lymphoma cell viability in vitro, trypan blue exclusion assay was performed on canine B-cell lymphoma cell lines (17-71 and CLBL) and primary B-cell lymphoma cells from the nodal tissue of four dogs. A doxycycline concentration of 6 µg/ml decreased canine lymphoma cell viability by 80%, compared to matched, untreated, control cells (mixed model analysis, p < 0.0001; Wilcoxon signed rank test, p = 0.0313). Although the short-term administration of oral doxycycline is not associated with the remission of canine lymphoma, combination therapy may be worthwhile if future research determines that doxycycline can alter cell survival pathways in canine lymphoma cells. Due to the potential for metabolic abnormalities, close monitoring is recommended with the use of this drug in tumor-bearing dogs. Additional research is needed to assess the tolerability of chronic doxycycline therapy.

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“…29 Altered expression of these enzymes is critical in different physiological and pathological processes and has been investigated in numerous feline conditions. 2,31,32,39,41 Sorensen et al 36 evaluated a group of MMPs on fresh FISS biopsies with reverse transcriptase-polymerase chain reaction (RT-PCR), showing that MMP-2 and membrane type-MMP-16 were correlated with survival time.…”

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confidence: 99%

Feline Injection-Site Sarcoma

et al. 2016

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Feline injection-site sarcoma (FISS) is an aggressive tumor believed to arise from the proliferation of fibroblasts and myofibroblasts in areas of chronic inflammation, particularly at sites of injection. Local recurrence is frequent after surgical excision. Gelatinases (MMP-2 and MMP-9) and their inhibitor (TIMP-2) are endopeptidases pivotal in extracellular matrix remodeling and therefore in tumor invasiveness. The aim of this study was to investigate the immunohistochemical expression of MMP-2, MMP-9, and TIMP-2 in FISS to assess their usefulness as prognostic factors. Size, soft tissue sarcoma (STS) grading system, depth of infiltration, surgical margins, and Ki-67 index were evaluated as additional prognostic markers. Twenty-four cases of primary FISS were classified according to clinical follow-up as nonrecurrent (NR, n = 14; 58.3%) and recurrent (R, n = 10; 41.7%). MMP-2, MMP-9, and TIMP-2 were variably expressed in the FISS examined, confirming their role in tumor invasiveness, yet they did not show significant differences between the R and NR groups. These results could be due to different tumor stages or to the multiple activities of these enzymes, not limited to ECM remodeling. The immunohistochemical expression of these enzymes considered alone does not seem to be useful as a prognostic marker. STS grading system, depth of infiltration, surgical margins, and Ki-67 index did not relate to recurrence. Instead, the size of the tumor, measured after formalin fixation, with an optimal cutoff of 3.75 cm (accuracy = 86%; P < .05), and the mitotic count, with an optimal cutoff of 20 mitoses/10 HPF (accuracy = 80%; P < .05), could be evaluated as useful prognostic markers.

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Plasma matrix metalloproteinase‐9 activity in cats with lymphoma

Cited by 5 publications

References 14 publications

CD147 and Cyclooxygenase Expression in Feline Oral Squamous Cell Carcinoma

CD147 and Cyclooxygenase Expression in Feline Oral Squamous Cell Carcinoma

Metabolic Abnormalities Detected in Phase II Evaluation of Doxycycline in Dogs with Multicentric B-Cell Lymphoma

Feline Injection-Site Sarcoma

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