Monocyte Phenotypic and Functional Differences
| Status: | Completed |
|---|---|
| Conditions: | Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 6 - Any |
| Updated: | 7/1/2018 |
| Start Date: | October 2014 |
| End Date: | March 23, 2017 |
A Canine/ Human Translational Model of Phenotypic and Functional Differences Between Monocytes in Patients With and Without Sarcoma
The purpose of this study is to identify phenotypic (cell surface receptor expression) and
functional differences in monocyte populations in humans with osteosarcoma as compared to
published historical data on normal human monocyte values.
The biologic similarity between canine and human osteosarcoma makes it a disease model that
holds promise for translational research possibilities. The phenotypic and functional
differences the investigators expect to find in canine and human monocytes between normal and
osteosarcoma subjects in this pilot work will allow us to launch a program of investigations
to further their understanding as to what characteristics are associated with improved
survival in canine and human osteosarcoma. Such data will represent the foundation upon which
the investigators can plan future investigations designed to exploit the potential anti-tumor
capabilities of monocytes and macrophages in canine and human osteosarcoma.
functional differences in monocyte populations in humans with osteosarcoma as compared to
published historical data on normal human monocyte values.
The biologic similarity between canine and human osteosarcoma makes it a disease model that
holds promise for translational research possibilities. The phenotypic and functional
differences the investigators expect to find in canine and human monocytes between normal and
osteosarcoma subjects in this pilot work will allow us to launch a program of investigations
to further their understanding as to what characteristics are associated with improved
survival in canine and human osteosarcoma. Such data will represent the foundation upon which
the investigators can plan future investigations designed to exploit the potential anti-tumor
capabilities of monocytes and macrophages in canine and human osteosarcoma.
Research on canine osteosarcoma lends itself well to comparative studies of osteosarcoma in
humans because dogs develop spontaneous tumors which are similar to human cancers with the
added benefit of frequently being more prevalent1. Osteosarcoma is diagnosed in more than
8000 dogs every year, and it affects mostly middle-aged to older dogs.2 The majority (75%) of
canine osteosarcoma occurs in the appendicular skeleton.3 Osteosarcoma is diagnosed in 1-3
million humans every year, and is a disease primarily of those between 10 and 25 years old.
Human osteosarcoma also occurs primarily in the appendicular skeleton, and like dogs, is most
often found in the metaphyses of long bones. Pulmonary metastasis is the most common site of
spread in dogs and humans, and is usually the cause of death in patients that have undergone
standard of care therapy (surgical resection of tumor, chemotherapy).4 The reported median
survival times for canine osteosarcoma have plateaued with no notable improvements in the
last 20 years, despite attempts at various permutations of adjunctive chemotherapy.5,6,7
Targeting metastatic disease will be the key to improving survival in both canine and human
osteosarcoma.
Interestingly, there is one arena in which median survival times in osteosarcoma have been
extended - patients who develop infections after limb-spare surgery have been observed to
double their median survival time. Lascelles et al. noted that infected dogs were half as
likely to die, half as likely to develop metastasis, and these survival effects were due to a
delay in metastasis rather than control of local tumor recurrence.8 A similar phenomenon of
increased survival in infected human osteosarcoma patients has been observed. Jeys et
al.reported that the 10-year survival rate in humans was significantly better in infected
limb-spares: 84.5% in the infected patients versus 62.2% in the non-infected patients.9 An
upregulation of antitumor immunity has been postulated to be potentially responsible for the
favorable survivals in the face of an infection in dogs and humans. Characterization of the
phenotype and function of circulating canine and human monocytes in normal subjects, and in
osteosarcoma subjects with and without an infection will be crucial in furthering their
understanding of how these cells are involved in the pathogenesis and potential suppression
of osteosarcoma.
humans because dogs develop spontaneous tumors which are similar to human cancers with the
added benefit of frequently being more prevalent1. Osteosarcoma is diagnosed in more than
8000 dogs every year, and it affects mostly middle-aged to older dogs.2 The majority (75%) of
canine osteosarcoma occurs in the appendicular skeleton.3 Osteosarcoma is diagnosed in 1-3
million humans every year, and is a disease primarily of those between 10 and 25 years old.
Human osteosarcoma also occurs primarily in the appendicular skeleton, and like dogs, is most
often found in the metaphyses of long bones. Pulmonary metastasis is the most common site of
spread in dogs and humans, and is usually the cause of death in patients that have undergone
standard of care therapy (surgical resection of tumor, chemotherapy).4 The reported median
survival times for canine osteosarcoma have plateaued with no notable improvements in the
last 20 years, despite attempts at various permutations of adjunctive chemotherapy.5,6,7
Targeting metastatic disease will be the key to improving survival in both canine and human
osteosarcoma.
Interestingly, there is one arena in which median survival times in osteosarcoma have been
extended - patients who develop infections after limb-spare surgery have been observed to
double their median survival time. Lascelles et al. noted that infected dogs were half as
likely to die, half as likely to develop metastasis, and these survival effects were due to a
delay in metastasis rather than control of local tumor recurrence.8 A similar phenomenon of
increased survival in infected human osteosarcoma patients has been observed. Jeys et
al.reported that the 10-year survival rate in humans was significantly better in infected
limb-spares: 84.5% in the infected patients versus 62.2% in the non-infected patients.9 An
upregulation of antitumor immunity has been postulated to be potentially responsible for the
favorable survivals in the face of an infection in dogs and humans. Characterization of the
phenotype and function of circulating canine and human monocytes in normal subjects, and in
osteosarcoma subjects with and without an infection will be crucial in furthering their
understanding of how these cells are involved in the pathogenesis and potential suppression
of osteosarcoma.
Inclusion Criteria:
- Patients presenting for evaluation of osteosarcoma of the appendicular skeleton
- Patient is 6years or older at time of visit
- Patients do not need to be eligible for surgery
- Patients may have known infection related to osteosarcoma and its treatment (ex.
surgical wound infection)
- Patients who would normally have a blood draw as part of their standard care
Exclusion Criteria:
- Patients younger than 10 years of age
- Patients who are unwilling/unable to undergo blood draw
- Patients with known infection unrelated to osteosarcoma or its treatment
- Patients with known systemic immune-mediated disease including but not limited to
lymphoma, AIDS/HIV, Lupus, etc.
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