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Joseph A. Bauer & Gerald Frye & Anne Bahr & Jennifer Gieg & Peter Brofman
Anti-tumor effects of nitrosylcobalamin against spontaneous tumors in dogs
Invest New Drugs
Publ. online: 27 June 2009
DOI 10.1007/s10637-009-9282-0
Summary Purpose: Given the limited options available to
treat canine cancers, the use of companion animals for
evaluating new drugs may identify better therapies for
veterinary and human oncology. The anti-tumor effects of
nitrosylcobalamin (NO-Cbl), an apoptosis-inducing, vitamin
B12-based carrier of nitric oxide (NO), was evaluated
in four dogs with spontaneous cancer. Experimental
Design: (1) A 13 year-old female spayed Giant Schnauzer
with inoperable thyroid carcinoma and hypercalcemia. (2)
A 6 year-old male neutered Golden Retriever with a
malignant peripheral nerve sheath tumor (MPNST). (3) A
ten yr-old neutered male Bichon Frise with apocrine gland
anal sac adenocarcinoma (AGACA). (4) A 7 year-old
female spayed Labrador mix with spinal meningioma
following partial surgical resection. Tumor regression was
measured by physical exam and verified using ultrasound
(case 1) and MRI (case 2–4). Serum chemistries and
hematologic parameters were monitored throughout the
studies. Results: (1) The Giant Schnauzer demonstrated a
77% reduction in tumor volume after ten weeks of daily
NO-Cbl treatment. (2) The Golden Retriever demonstrated
a 53% reduction in tumor volume after 15 months of daily
NO-Cbl therapy. (3) The Bichon Frise demonstrated a 43%
regression of the primary tumor and a 90% regression of an
iliac lymph node measured by MRI after 15 months of
treatment. After 61 months, the dog currently has stable
disease, normal liver enzymes, CBC analysis, and no
evidence of toxicity. (4) The Labrador demonstrated
complete regression of the residual tumor after 6 months
of treatment. Conclusion: We have shown previously that
NO-Cbl is endocytosed by malignant cells, resulting in
intra-tumoral NO release. In this study, we have shown that
daily long-term use of NO-Cbl induced responses in all
dogs without any signs of toxicity. The use of NO-Cbl
capitalizes on the tumor-specific properties of the vitamin
B12 receptor and represents a promising anti-cancer
therapy.
Anti-tumor effects of nitrosylcobalamin against spontaneous tumors in dogs
Invest New Drugs
Publ. online: 27 June 2009
DOI 10.1007/s10637-009-9282-0
Summary Purpose: Given the limited options available to
treat canine cancers, the use of companion animals for
evaluating new drugs may identify better therapies for
veterinary and human oncology. The anti-tumor effects of
nitrosylcobalamin (NO-Cbl), an apoptosis-inducing, vitamin
B12-based carrier of nitric oxide (NO), was evaluated
in four dogs with spontaneous cancer. Experimental
Design: (1) A 13 year-old female spayed Giant Schnauzer
with inoperable thyroid carcinoma and hypercalcemia. (2)
A 6 year-old male neutered Golden Retriever with a
malignant peripheral nerve sheath tumor (MPNST). (3) A
ten yr-old neutered male Bichon Frise with apocrine gland
anal sac adenocarcinoma (AGACA). (4) A 7 year-old
female spayed Labrador mix with spinal meningioma
following partial surgical resection. Tumor regression was
measured by physical exam and verified using ultrasound
(case 1) and MRI (case 2–4). Serum chemistries and
hematologic parameters were monitored throughout the
studies. Results: (1) The Giant Schnauzer demonstrated a
77% reduction in tumor volume after ten weeks of daily
NO-Cbl treatment. (2) The Golden Retriever demonstrated
a 53% reduction in tumor volume after 15 months of daily
NO-Cbl therapy. (3) The Bichon Frise demonstrated a 43%
regression of the primary tumor and a 90% regression of an
iliac lymph node measured by MRI after 15 months of
treatment. After 61 months, the dog currently has stable
disease, normal liver enzymes, CBC analysis, and no
evidence of toxicity. (4) The Labrador demonstrated
complete regression of the residual tumor after 6 months
of treatment. Conclusion: We have shown previously that
NO-Cbl is endocytosed by malignant cells, resulting in
intra-tumoral NO release. In this study, we have shown that
daily long-term use of NO-Cbl induced responses in all
dogs without any signs of toxicity. The use of NO-Cbl
capitalizes on the tumor-specific properties of the vitamin
B12 receptor and represents a promising anti-cancer
therapy.
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