Dataset Information

Prognostic significance of circulating microRNA-214 and -126 in dogs with appendicular osteosarcoma receiving amputation and chemotherapy.

ABSTRACT: BACKGROUND:Dogs with appendicular osteosarcoma (OSA) receiving standard amputation and adjuvant chemotherapy demonstrate variable outcome with treatment; however, additional biomarkers would be helpful for predicting their outcome. In the present study, we assessed the potential of circulating microRNA-214 (miR-214) and?-?126 (miR-126) to predict time to metastasis and death in dogs with OSA treated with amputation and chemotherapy. RESULTS:Seventy-six dogs that fully met inclusion criteria were included in the analysis. The criteria included (1) a diagnosis of appendicular OSA without metastases at diagnosis, (2) treatment by amputation and chemotherapy using carboplatin, doxorubicin, cisplatin, or a combination of these agents. Circulating miR-214 and -126 levels at the time before treatment were measured by using RT-qPCR. High circulating miR-214 and serum alkaline phosphatase (ALP) significantly predicted short disease-free survival (DFS) and overall survival (OS). Conversely, high circulating miR-126 significantly predicted prolonged DFS and OS. An integrated approach using circulating miR-214, -?126, and serum ALP showed better accuracy in the prediction of DFS and OS and identification of long-term survivors than prediction using only ALP. Other variables (age, weight, sex, monocyte counts, and primary tumor site) were associated with neither DFS nor OS. miRNA levels did not strongly correlate with histopathological indices. CONCLUSIONS:Circulating miR-214, -?126, and an integrated prognostic score have strong potential to predict the outcome of canine appendicular OSA patients receiving amputation and chemotherapy.

SUBMITTER: Heishima K

PROVIDER: S-EPMC6347759 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Prognostic significance of circulating microRNA-214 and -126 in dogs with appendicular osteosarcoma receiving amputation and chemotherapy.

Heishima Kazuki K Meuten Travis T Yoshida Kyoko K Mori Takashi T Thamm Douglas H DH

BMC veterinary research 20190125 1

<h4>Background</h4>Dogs with appendicular osteosarcoma (OSA) receiving standard amputation and adjuvant chemotherapy demonstrate variable outcome with treatment; however, additional biomarkers would be helpful for predicting their outcome. In the present study, we assessed the potential of circulating microRNA-214 (miR-214) and - 126 (miR-126) to predict time to metastasis and death in dogs with OSA treated with amputation and chemotherapy.<h4>Results</h4>Seventy-six dogs that fully met inclusio ...[more]

PMID: 30683101

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Project description:BackgroundWe hypothesized that the addition of toceranib to metronomic cyclophosphamide/piroxicam therapy would significantly improve disease-free interval (DFI) and overall survival (OS) in dogs with appendicular osteosarcoma (OSA) following amputation and carboplatin chemotherapy.Methods and findingsThis was a randomized, prospective clinical trial in which dogs with OSA free of gross metastatic disease (n = 126) received carboplatin chemotherapy (4 doses) following amputation. On study entry, dogs were randomized to receive piroxicam/cyclophosphamide with or without toceranib (n = 63 each) after completing chemotherapy. Patient demographics were not significantly different between both groups. During or immediately following carboplatin chemotherapy, 32 dogs (n = 13 toceranib; n = 19 control) developed metastatic disease, and 13 dogs left the study due to other medical conditions or owner preference. Following carboplatin chemotherapy, 81 dogs (n = 46 toceranib; n = 35 control) received the metronomic treatment; 35 dogs (n = 20 toceranib; n = 15 control) developed metastatic disease during the maintenance therapy, and 26 dogs left the study due to other medical conditions or owner preference. Nine toceranib-treated and 11 control dogs completed the study without evidence of metastatic disease 1-year following amputation. Toceranib-treated dogs experienced more episodes of diarrhea, neutropenia and weight loss than control dogs, although these toxicities were low-grade and typically resolved with supportive care. More toceranib-treated dogs (n = 8) were removed from the study for therapy-associated adverse events compared to control dogs (n = 1). The median DFI for control and toceranib treated dogs was 215 and 233 days, respectively (p = 0.274); the median OS for control and toceranib treated dogs was 242 and 318 days, respectively (p = 0.08). The one year survival rate for control dogs was 35% compared to 38% for dogs receiving toceranib.ConclusionsThe addition of toceranib to metronomic piroxicam/cyclophosphamide therapy following amputation and carboplatin chemotherapy did not improve median DFI, OS or the 1-year survival rate in dogs with OSA.

Project description:This study aimed to characterize bone cancer pain (quantitative sensory testing (QST), stance asymmetry index, actimetry, scores of pain and quality of life (QoL)) in dogs with appendicular osteosarcoma (OSA), and to evaluate a stepwise palliative analgesic treatment. The pain profile of thirteen client-owned dogs with OSA was compared with seven healthy dogs. Dogs with OSA were then enrolled in a prospective, open-label, clinical trial. Outcome measures included: primary and secondary mechanical thresholds (MT), conditioned pain modulation (CPM), stance asymmetry index, actimetry (most and least active periods), visual analog scales and QoL. After baseline assessments, stepwise treatment comprised orally administered cimicoxib (2 mg/kg q 24h), amitriptyline (1-1.5 mg/kg q 24h) and gabapentin (10 mg/kg q 8h); re-evaluations were performed after 14 (D14), 21 (D21) and 28 (D28) days, respectively. Statistics used mixed linear models (? = 5%; one-sided). Centralized nociceptive sensitivity (primary and secondary MT, and dynamic allodynia) was recorded in OSA dogs. Healthy dogs had responsive CPM, but CPM was deficient in OSA dogs. Construct validity was observed for the QST protocol. Asymmetry index was significantly present in OSA dogs. The CPM improved significantly at D14. When compared with baseline (log mean ± SD: 4.1 ± 0.04), most active actimetry significantly improved at D14 (4.3 ± 0.04), D21 and D28 (4.2 ± 0.04 for both). When compared with baseline, least active actimetry significantly decreased after treatment at all time-points indicating improvement in night-time restlessness. No other significant treatment effect was observed. Except for tactile threshold and actimetry, all outcomes worsened when gabapentin was added to cimicoxib-amitriptyline. Dogs with bone cancer are affected by widespread somatosensory sensitivity characterized by peripheral and central sensitization and have a deficient inhibitory system. This severe pain is mostly refractory to palliative analgesic treatment, and the latter was only detected by specific and sensitive outcomes.

Dataset Information

Prognostic significance of circulating microRNA-214 and -126 in dogs with appendicular osteosarcoma receiving amputation and chemotherapy.

Publications

Prognostic significance of circulating microRNA-214 and -126 in dogs with appendicular osteosarcoma receiving amputation and chemotherapy.

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