Characterizing Circulating Nucleosomes in the Plasma of Dogs with Lymphoma

2021 ◽  
Author(s):  
Christopher Dolan ◽  
Tasha Miller ◽  
Jarvis Jill ◽  
Jason Terrell ◽  
Theresa Kelly ◽  
...  
Keyword(s):  
Fold Increase ◽  
Monitoring Tool ◽  
Treatment Results ◽  
Canine Lymphoma ◽  
Histone Octamer ◽  
Objective Monitoring ◽  
Remission Status ◽  
T Cell Lymphomas ◽  
Healthy Dogs ◽  
Multicentric Lymphoma

Abstract Background: Nucleosomes consist of DNA wrapped around a histone octamer core like beads on a string so that DNA can be condensed as chromatin into chromosomes. Diseases such as cancer or inflammation lead to cell death where chromatin is fragmentated and released as mononucleosomes into the blood. The Nu.QTM H3.1 assay measures total nucleosome concentration in plasma of humans and has been used to detect and identify cancer even at early stages. The objectives of this study were to determine if nucleosome levels could be used to distinguish between healthy dogs and dogs with various stages of lymphoma (LSA) using the Nu.Q™ H3.1 assay. A total of 126 dogs diagnosed with LSA and 134 healthy controls were recruited for this study. Plasma was collected from each dog and stored in K2-EDTA tubes. The LSA patient samples were recruited from TAMU or purchased from various biobanks. All control cases were recruited from TAMU. Samples were also collected longitudinally from 3 dogs undergoing treatment for multicentric lymphoma at TAMU as a pilot study to investigate the pattern of nucleosome concentrations in plasma during treatment. Results: Dogs with LSA had an approximately 7-fold increase in their plasma nucleosome concentrations compared to controls (AUC 87.8%). Nucleosome concentrations increased with cancer stage and dogs with B cell lymphomas had significantly higher nucleosome concentrations than dogs with T cell lymphomas. Nucleosome concentrations from serially monitored patients were elevated at diagnosis and progression with subsequent decreases in nucleosome concentration that corresponded to clinically detectable responses to therapy. Conclusions: The Nu.QTM H3.1 assay was able to reliably detect elevated nucleosome concentrations in the plasma of dogs with LSA. Furthermore, it appears that nucleosomes are useful for differentiating cancer from healthy individuals in canines. Results from serially monitored patients indicate that nucleosomes could be an objective monitoring tool for remission status in canine lymphoma patients.

scholarly journals Characterizing circulating nucleosomes in the plasma of dogs with lymphoma

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Christopher Dolan ◽  
Tasha Miller ◽  
Jarvis Jill ◽  
Jason Terrell ◽  
Theresa Kathleen Kelly ◽  
...  
Keyword(s):  
Cell Death ◽  
T Cell ◽  
B Cell ◽  
Fold Increase ◽  
Cancer Stage ◽  
Healthy Controls ◽  
Healthy Individuals ◽  
Histone Octamer ◽  
T Cell Lymphomas ◽  
Healthy Dogs

Abstract Background Nucleosomes consist of DNA wrapped around a histone octamer core like beads on a string so that DNA can be condensed as chromatin into chromosomes. Diseases such as cancer or inflammation lead to cell death where chromatin is fragmentated and released as mononucleosomes into the blood. The Nu.Q™ H3.1 assay measures total nucleosome concentration in plasma of humans and has been used to detect and identify cancer even at early stages. The objectives of this study were to determine if nucleosome levels could be used to distinguish between healthy dogs and dogs with various stages of lymphoma (LSA) using the Nu.Q™ H3.1 assay. A total of 126 dogs diagnosed with LSA and 134 healthy controls were recruited for this study. Plasma was collected from each dog and stored in K2-EDTA tubes. The LSA patient samples were recruited from TAMU or purchased from various biobanks. All control cases were recruited from TAMU. Results Dogs with LSA had an approximately 7-fold increase in their plasma nucleosome concentrations compared to controls (AUC 87.8%). Nucleosome concentrations increased with cancer stage and dogs with B cell lymphomas had significantly higher nucleosome concentrations than dogs with T cell lymphomas. Conclusions The Nu.Q™ H3.1 assay was able to reliably detect elevated nucleosome concentrations in the plasma of dogs with LSA. Furthermore, it appears that nucleosomes are useful for differentiating cancer from healthy individuals in canines.

scholarly journals Characterizing circulating nucleosomes in the plasma of dogs with hemangiosarcoma

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Heather Wilson-Robles ◽  
Tasha Miller ◽  
Jill Jarvis ◽  
Jason Terrell ◽  
Theresa Kathleen Kelly ◽  
...  
Keyword(s):  
Cell Death ◽  
Small Animal ◽  
Fold Increase ◽  
Healthy Controls ◽  
Histone Octamer ◽  
Early Stages ◽  
Median Plasma ◽  
Healthy Dogs ◽  
Control Samples

Abstract Background Nucleosomes consist of DNA wrapped around a histone octamer core like thread on a spool to condense DNA as chromatin into chromosomes. Diseases such as cancer or inflammation lead to cell death, chromatin fragmentation and release of nucleosomes into the blood. The Nu.Q™ platform measures circulating nucleosomes in the blood of humans that result from disease and has been used to detect and identify cancer even at early stages. The objectives of this study are to quantify and better characterize nucleosomes in dogs with various stages of hemangiosarcoma (HSA) using this ELISA-based assay. Samples from 77 dogs with a confirmed diagnosis of hemangiosarcoma and 134 healthy controls were utilized for this study. The HSA samples were recruited from the Texas A&M University Small Animal Clinic (TAMU-SAC) or purchased from biobanks. All control samples were recruited from the TAMU-SAC. Results Dogs with hemangiosarcoma had a 6.6-fold increase in their median plasma nucleosome concentrations compared to controls (AUC 92.9 %). Elevated nucleosome concentrations were seen at all stages of disease and nucleosome concentrations increased with the stage of the disease. Conclusions Plasma nucleosome concentrations are a reliable way to differentiate dogs with hemangiosarcoma from healthy dogs. Further testing is underway to better characterize cancer associated HSA circulating nucleosomes and optimize future diagnostics for canine HSA detection.

scholarly journals Regulatory T cells in dogs with multicentric lymphoma: peripheral blood quantification at diagnosis and after initial stage chemotherapy

2016 ◽  
Vol 68 (1) ◽  
pp. 1-9
Author(s):  
T.D. Munhoz ◽  
L.A. Anai ◽  
D.M. Fonseca ◽  
L.M. Semolin ◽  
F.R. Sueiro ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Peripheral Blood ◽  
Cell Subpopulation ◽  
Chemotherapy Treatment ◽  
Canine Lymphoma ◽  
Hematopoietic Malignancy ◽  
Initial Stage ◽  
Healthy Dogs ◽  
Multicentric Lymphoma

Lymphoma is the most common hematopoietic malignancy in dogs and one of the most frequent among all neoplastic diseases in this species. It can occur in several anatomical locations with distinct histological and immunophenotypes. Depending on the host immune response towards the tumor, prognosis information could be collected. Because its well established immunosuppressant, antitumor activity, the function of regulatory T cells (Tregs) in canine neoplasias has been investigated. In this study, we sought to quantify, using flow cytometry, the Tregs subpopulation in peripheral blood of healthy dogs (10) and in those diagnosed with type-B (14) and type-T (8) multicentric lymphoma before (at diagnosis) and after the first cycle (5-week) of 19-week Madison-Wisconsin (MW) protocol of chemotherapy. Our results indicated that dogs with lymphoma showed higher percentage of Tregs (18,84±2,56) when compared to healthy dogs (4,70±0,50) (P<0,01). In addition, 5-week chemotherapy treatment reduced the Tregs subpopulation (7,54±1,08) to levels similar to control (4,70±0,50) (P>0,05). There was no difference in Tregs percentage between B-type (17,45±2,77) and T-type (21,27±5,27) lymphoma (P>0,05). With this, we conclude that canine lymphoma increases Tregs in the peripheral blood and the MW protocol of chemotherapy reduces this cell subpopulation to control values.

scholarly journals Characterizing Circulating Nucleosomes in the Plasma of Dogs with Hemangiosarcoma

2021 ◽  
Author(s):  
Heather Wilson-Robles ◽  
Jason Terrell ◽  
Theresa Kathleen Kelly ◽  
Tasha Miller ◽  
Bygott Thomas ◽  
...  
Keyword(s):  
Cell Death ◽  
Small Animal ◽  
Fold Increase ◽  
Healthy Controls ◽  
Histone Octamer ◽  
Early Stages ◽  
Median Plasma ◽  
Healthy Dogs ◽  
Control Samples

Abstract Background: Nucleosomes consist of DNA wrapped around a histone octamer core like thread on a spool to condense DNA as chromatin into chromosomes. Diseases such as cancer or inflammation lead to cell death, chromatin fragmentation and release of nucleosomes into the blood. The Nu.QTM platform measures circulating nucleosomes in the blood of humans that result from disease and has been used to detect and identify cancer even at early stages. The objectives of this study are to quantify and better characterize nucleosomes in dogs with various stages of hemangiosarcoma (HSA) using this ELISA-based assay. Samples from 77 dogs with a confirmed diagnosis of hemangiosarcoma and 134 healthy controls were utilized for this study. The HSA samples were recruited from the Texas A&M University Small Animal Clinic (TAMU-SAC) or purchased from biobanks. All control samples were recruited from the TAMU-SAC. Results: Dogs with hemangiosarcoma had a 6.6-fold increase in their median plasma nucleosome concentrations compared to controls (AUC 92.9%). Elevated nucleosome concentrations were seen at all stages of disease and nucleosome concentrations increased with the stage of the disease. Conclusion: Plasma nucleosome concentrations are a reliable way to differentiate dogs with hemangiosarcoma from healthy dogs. Further testing is underway to better characterize cancer associated HSA circulating nucleosomes and optimize future diagnostics for canine HSA detection.

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

Animals ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 2199
Author(s):  
Jih-Jong Lee ◽  
Albert Taiching Liao ◽  
Shang-Lin Wang
Keyword(s):  
Clinical Stage ◽  
Progression Free Survival ◽  
Cell Phenotype ◽  
Chop Chemotherapy ◽  
First Line ◽  
Canine Lymphoma ◽  
Free Survival ◽  
Significant Difference ◽  
Multicentric Lymphoma ◽  
First Line Treatment

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.

cAMP, myosin dephosphorylation, and isometric relaxation of airway smooth muscle

1988 ◽  
Vol 64 (2) ◽  
pp. 705-709 ◽  
Author(s):  
P. de Lanerolle
Keyword(s):  
Smooth Muscle ◽  
Steady State ◽  
Muscle Relaxation ◽  
Fold Increase ◽  
Treatment Results ◽  
Myosin Phosphorylation ◽  
Temporal Relationships ◽  
Steady State Levels ◽  
Two Parameters ◽  
Camp Levels

The temporal relationships among increases in adenosine 3',5'-cyclic monophosphate (cAMP) levels, myosin dephosphorylation, and relaxation were investigated to clarify the mechanisms of airway muscle relaxation. Canine tracheal muscles isometrically contracted (82% of maximum force) with 10(-6) M methacholine were relaxed by adding either 4 x 10(-7) M atropine or 4 x 10(-5) M forskolin. Atropine had no effect on cAMP levels; myosin phosphorylation and force, however, decayed at the same rates and these two parameters returned to their basal pre-methacholine levels within 5 min. Forskolin treatment results in about a 10-fold increase in cAMP levels; myosin phosphorylation and force decayed simultaneously to their respective steady-state levels by 10 min but neither parameter returned to its pre-methacholine level. The addition of forskolin to muscles maximally contracted with 10(-4) M methacholine leads to about a 30-fold increase in cAMP levels. However, there are minimal decreases in myosin phosphorylation and force in these muscles. Thus myosin dephosphorylation appears to be essential for airway muscle relaxation, whereas an increase in cAMP in the absence of myosin dephosphorylation is insufficient to cause relaxation. Moreover, myosin dephosphorylation appears to be a common step in the cAMP-independent and cAMP-dependent mechanisms for airway muscle relaxation.

scholarly journals Histopathological and immunophenotypical characterization of canine multicentric lymphoma in Brazil: a study of 203 cases

2020 ◽  
Vol 72 (3) ◽  
pp. 787-793
Author(s):  
P.C. Jark ◽  
C.P. Fracacio ◽  
L.A. Anai ◽  
M.C.L. Silva ◽  
S.G. Calazans ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Cell Line ◽  
B Cell Lymphoma ◽  
High Grade ◽  
Canine Lymphoma ◽  
The Usa ◽  
T Cell Lines ◽  
Multicentric Lymphoma

ABSTRACT The immunophenotype is regarded as an independent prognostic factor in high-grade lymphomas, seeing that lymphomas of T-cell origin are associated with shorter survival time. Although a number of studies have evaluated the immunophenotypical profile of lymphoma in the USA and Europe, Brazilian research on the matter remains scarce. Exact characterization of the histopathological type is crucial to establish proper treatment and prognosis. This study evaluated the database of immunohistochemistry laboratories that perform immunophenotyping of canine lymphoma in Brazil. A total of 203 cases of multicentric lymphoma were classified according to the WHO classification. Immunophenotyping was able to identify 71.4% lymphomas of B-cell line, 27.1% of T-cell line and 1.5% of non-B cells and non-T cell lines. Diffuse large B-cell lymphoma was the most common with 59.1% of the cases. Among T-cell lymphomas, lymphoblastic was the most common (11.33% of the cases). Even though canine lymphomas tend to be high-grade, indolent lymphomas comprised 11.82% of the cases and T-zone lymphoma was the most prevalent (8.86%). The immunophenotype of multicentric lymphoma in Brazil is similar to those in other parts of the world, which suggests similar etiologic factors to the development of this disease.

Comparison of serum cytokine levels between dogs with multicentric lymphoma and healthy dogs

2016 ◽  
Vol 182 ◽  
pp. 106-114 ◽  
Author(s):  
Jerome Calvalido ◽  
Geoffrey A. Wood ◽  
Anthony J. Mutsaers ◽  
Darren Wood ◽  
William Sears ◽  
...  
Keyword(s):  
Serum Cytokine ◽  
Cytokine Levels ◽  
Healthy Dogs ◽  
Multicentric Lymphoma

scholarly journals Evaluation of nucleosome concentrations in healthy dogs and dogs with cancer

2020 ◽  
Author(s):  
H Wilson-Robles ◽  
T Miller ◽  
J Jarvis ◽  
J Terrell ◽  
N Dewsbury ◽  
...  
Keyword(s):  
Sample Type ◽  
Newly Diagnosed ◽  
Sample Collection ◽  
Serum Samples ◽  
Histone Octamer ◽  
Optimal Sample ◽  
Edta Plasma ◽  
Tube Type ◽  
Small Cohort ◽  
Healthy Dogs

AbstractIntroductionNucleosomes consist of small fragments of DNA wrapped around a histone octamer core. Diseases such as cancer or inflammation lead to cell death, which causes fragmentation and release of nucleosomes into the blood. The Nu.Q™ technology measures circulating nucleosome levels and exploits the different compositions of cancer derived nucleosomes in blood to detect and identify cancer even at early stages. The objectives of this study are to identify the optimal sample type for the Nu.Q™ H3.1 assay and to determine if it can accurately detect nucleosomes in the blood of healthy canines as well as those with cancer.Materials and MethodsBlood samples from healthy canine volunteers as well as dogs newly diagnosed with lymphoma were used. The blood was processed at a variety of times under a variety of conditions to determine the most reliable sample type and conditions, and to develop an appropriate processing strategy to ensure reliably accurate results.ResultsNucleosomes could be detected using a variety of sample collection and processing protocols. Nucleosome signals were highest in EDTA plasma and serum samples and most consistent in plasma. Samples should be processed within an hour of collection. Experiments showed that samples were able to withstand several freeze thaw cycles. Processing time and tcollection tube type did affect nucleosome detection levels. Finally, significantly elevated concentrations of nucleosomes were seen in a small cohort of dogs that had been newly diagnosed with lymphoma.ConclusionsWhen samples are collected and processed appropriately, the Nu.Q™ platform can reliably detect nucleosomes in the plasma of dogs. Further testing is underway to validate and optimize the Nu.Q™ platform for veterinary use.

Outcomes of autologous versus allogeneic hematopoietic stem cell transplantation for peripheral T-cell lymphomas: A multicenter retrospective study in china.

2020 ◽  
Author(s):  
Zhenyang Gu ◽  
Yujun Dong ◽  
Xiaorui Fu ◽  
Nainong Li ◽  
Yao Liu ◽  
...  
Keyword(s):  
Stem Cell ◽  
Retrospective Study ◽  
T Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Hematopoietic Stem ◽  
Remission Status ◽  
T Cell Lymphomas ◽  
Peripheral T Cell Lymphomas ◽  
Better Than

Abstract To date, there is no consensus on choosing autologous hematopoietic stem cell transplantation (auto-HSCT) or allogenic HSCT (allo-HSCT) for peripheral T-cell lymphomas (PTCLs). This study aimed to compare the relative efficacy of auto-HSCT versus allo-HSCT for patients with PTCLs. We conducted a multicenter retrospective study about 128 patients who underwent auto-HSCT (n=72) or allo-HSCT (n=56) at 8 medical centers across China between July, 2007 and June, 2017. With a median follow-up of 30 (2-143) months, outcomes of patients receiving auto-HSCT were better than those in allo-HSCT (3-year OS: 70% versus 46%, P = 0.003; 3-year PFS: 59% versus 44%, P = 0.002). Three-year non relapse rate (NRM) in auto-HSCT recipients was 6%, compared with 27% for allo-HSCT recipients ( P =0.004). There was no difference in relapse rate between these two groups (34% in auto-HSCT versus 29% in allo-HSCT, P =0.84). Specifically, patients with low PIT score who received auto-HSCT group in upfront setting had better outcome than patients with high PIT score (3-year OS: 85% versus 40%, P = 0.003). Regarding remission status before transplantation, patients with CR undergoing auto-HSCT had the best outcome (3-year OS: 88% versus 48% in allo-HSCT; P =0.008). For patients less than CR, the outcome of patients undergoing auto-HSCT was similar to that in allo-HSCT (3-year OS:51% versus 46%; P =0.30). When further checking patients in PD or SD, the survival curve of patients in the allo-HSCT group was better than that in the auto-HSCT group. It is plausible to choose auto-HSCT versus allo-HSCT according PIT score and remission status before transplantation.

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