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Daniel J. Lindner – One of the best experts on this subject based on the ideXlab platform.

  • Abstract #1771: Anti-tumor effects of nitrosylcobalamin (NO-Cbl) against spontaneous tumors in dogs
    Cancer Research, 2009
    Co-Authors: Joseph A. Bauer, Jennifer Gieg, Gerald Frye, Anne Bahr, Daniel J. Lindner
    Abstract:

    Background: Given the limited options available to treat canine cancers, the use of companion animals (pets) for evaluating new drugs may identify better therapies for veterinary and human oncology. Objective: The anti-tumor effects of nitrosylcobalamin (NO-Cbl), an apoptosis-inducing, vitamin B12 based carrier of nitric oxide (NO), was evaluated in three dogs with spontaneous carcinomas. Animals: (1) A 13 year-old female spayed Giant Schnauzer was diagnosed with inoperable thyroid carcinoma and hypercalcemia. (2) A 6 yr-old male neutered Golden Retriever presented malignant peripheral nerve sheath tumor (MPNST). (3) A ten yr-old castrated male Bichon Frise presented with apocrine gland Anal Sac Adenocarcinoma (AGACA) after previously failing multiple therapies. Methods: The dogs were administered single agent NO-Cbl 28 mg/kg s.c. b.i.d. In addition the Bichon Frise received 6 cycles of carboplatin during week 42 – 56 of treatment. Tumor regression was measured by physical exam and verified using ultrasound and MRI. Serum chemistries and hematologic parameters were monitored throughout the studies. Results: (1) The Giant Schnauzer demonstrated a 77% reduction in tumor volume compared to baseline after ten months of daily NO-Cbl treatment. (2) The Golden Retriever demonstrated a 39% reduction in tumor volume compared to pre-treatment after 9 months of daily NO-Cbl therapy. (3) The Bichon Frise demonstrated a 43% regression of the primary tumor and a 90% regression of the iliac lymph node measured by MRI after 15 months of treatment. After 53 months, the dog currently has stable disease, normal liver enzymes, CBC Analysis, and no evidence of toxicity. Clinical Significance: The use of vitamin B12 to deliver nitric oxide to tumors is novel. 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 partial 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. Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1771.

  • Phase I and pharmacokinetic study of sodium trans-[tetrachlorobis(1H-indazole)ruthenate(III)] / indazolehydrochloride (1:1.1) (FFC14A, KP1019) in patients with solid tumors – a study of the CESAR Central European Society for Anticancer Drug Research
    Cancer Research, 2005
    Co-Authors: Joseph A. Bauer, Bei H. Morrison, Zhuo Tang, Rhonda K. Oates, Joseph A. Lupica, Christine R. Anderson, Jean M. Poulson, Jennifer Gieg, Ernest C Borden, Daniel J. Lindner
    Abstract:

    471 Introduction: We evaluated the anti-neoplastic effects of nitrosylcobalamin (NO-Cbl) an apoptosis-inducing, vitamin B12 based carrier of nitric oxide (NO) in two dogs: 1.) a ten year old male Bichon Frise with aggressive Anal Sac Adenocarcinoma previously treated with adriamycin/radiation therapy and 2.) a 13 year old female Giant Schnauzer with parathyroid Adenocarcinoma previously treated with intra-tumor ethanol injection. Methods: Both dogs were given NO-Cbl 28 mg/kg/day s.c. which was increased to 42 mg/kg/day divided into two or three doses per day .Tumor regression was measured by physical exam and verified using CT, ultrasound and MRI. Summary of Data: After 15 weeks of daily NO-Cbl treatment, the male Bichon demonstrated a 50% regression in tumor volume based on physical exam and MR studies. No adverse side effects were noted as evidenced by normal liver enzyme levels, CBC Analysis, and normal creatinine levels, however BUN was elevated 3 times normal which may be a result of increased nitrate levels, a metabolite of NO-Cbl. After 10 weeks of NO-Cbl treatment, the female Giant Schnauzer demonstrated a 77% reduction in tumor volume, verified by ultrasound. Interestingly, she displayed normal blood chemistry (including BUN) and cell counts. Conclusion: The use of vitamin B12 to deliver nitric oxide to tumors is novel. We have shown previously that NO-Cbl is endocytosed by malignant cells resulting in intra-tumoral NO release. In this study, we show that daily long-term administration of NO-Cbl was effective in achieving partial responses in two canines with spontaneous tumors. Importantly, both dogs tolerated treatment extremely well, maintained normal blood chemistry, and showed no evidence of bone marrow suppression. The use of NO-Cbl capitalizes on the tumor specific properties of the vitamin B12 receptor (transcobalamin II, TCII receptor) expression and represents a promising anti-cancer therapy.

  • phase i and pharmacokinetic study of sodium trans tetrachlorobis 1h indazole ruthenate iii indazolehydrochloride 1 1 1 ffc14a kp1019 in patients with solid tumors a study of the cesar central european society for anticancer drug research ewiv
    Cancer Research, 2005
    Co-Authors: Joseph A. Bauer, Bei H. Morrison, Zhuo Tang, Rhonda K. Oates, Joseph A. Lupica, Christine R. Anderson, Jean M. Poulson, Jennifer Gieg, Ernest C Borden, Daniel J. Lindner
    Abstract:

    471 Introduction: We evaluated the anti-neoplastic effects of nitrosylcobalamin (NO-Cbl) an apoptosis-inducing, vitamin B12 based carrier of nitric oxide (NO) in two dogs: 1.) a ten year old male Bichon Frise with aggressive Anal Sac Adenocarcinoma previously treated with adriamycin/radiation therapy and 2.) a 13 year old female Giant Schnauzer with parathyroid Adenocarcinoma previously treated with intra-tumor ethanol injection. Methods: Both dogs were given NO-Cbl 28 mg/kg/day s.c. which was increased to 42 mg/kg/day divided into two or three doses per day .Tumor regression was measured by physical exam and verified using CT, ultrasound and MRI. Summary of Data: After 15 weeks of daily NO-Cbl treatment, the male Bichon demonstrated a 50% regression in tumor volume based on physical exam and MR studies. No adverse side effects were noted as evidenced by normal liver enzyme levels, CBC Analysis, and normal creatinine levels, however BUN was elevated 3 times normal which may be a result of increased nitrate levels, a metabolite of NO-Cbl. After 10 weeks of NO-Cbl treatment, the female Giant Schnauzer demonstrated a 77% reduction in tumor volume, verified by ultrasound. Interestingly, she displayed normal blood chemistry (including BUN) and cell counts. Conclusion: The use of vitamin B12 to deliver nitric oxide to tumors is novel. We have shown previously that NO-Cbl is endocytosed by malignant cells resulting in intra-tumoral NO release. In this study, we show that daily long-term administration of NO-Cbl was effective in achieving partial responses in two canines with spontaneous tumors. Importantly, both dogs tolerated treatment extremely well, maintained normal blood chemistry, and showed no evidence of bone marrow suppression. The use of NO-Cbl capitalizes on the tumor specific properties of the vitamin B12 receptor (transcobalamin II, TCII receptor) expression and represents a promising anti-cancer therapy.

Joseph A. Bauer – One of the best experts on this subject based on the ideXlab platform.

  • Anti-tumor effects of nitrosylcobalamin against spontaneous tumors in dogs
    Investigational New Drugs, 2010
    Co-Authors: Joseph A. Bauer, Jennifer Gieg, Gerald Frye, Anne Bahr, Peter Brofman
    Abstract:

    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.

  • Abstract #1771: Anti-tumor effects of nitrosylcobalamin (NO-Cbl) against spontaneous tumors in dogs
    Cancer Research, 2009
    Co-Authors: Joseph A. Bauer, Jennifer Gieg, Gerald Frye, Anne Bahr, Daniel J. Lindner
    Abstract:

    Background: Given the limited options available to treat canine cancers, the use of companion animals (pets) for evaluating new drugs may identify better therapies for veterinary and human oncology. Objective: The anti-tumor effects of nitrosylcobalamin (NO-Cbl), an apoptosis-inducing, vitamin B12 based carrier of nitric oxide (NO), was evaluated in three dogs with spontaneous carcinomas. Animals: (1) A 13 year-old female spayed Giant Schnauzer was diagnosed with inoperable thyroid carcinoma and hypercalcemia. (2) A 6 yr-old male neutered Golden Retriever presented malignant peripheral nerve sheath tumor (MPNST). (3) A ten yr-old castrated male Bichon Frise presented with apocrine gland Anal Sac Adenocarcinoma (AGACA) after previously failing multiple therapies. Methods: The dogs were administered single agent NO-Cbl 28 mg/kg s.c. b.i.d. In addition the Bichon Frise received 6 cycles of carboplatin during week 42 – 56 of treatment. Tumor regression was measured by physical exam and verified using ultrasound and MRI. Serum chemistries and hematologic parameters were monitored throughout the studies. Results: (1) The Giant Schnauzer demonstrated a 77% reduction in tumor volume compared to baseline after ten months of daily NO-Cbl treatment. (2) The Golden Retriever demonstrated a 39% reduction in tumor volume compared to pre-treatment after 9 months of daily NO-Cbl therapy. (3) The Bichon Frise demonstrated a 43% regression of the primary tumor and a 90% regression of the iliac lymph node measured by MRI after 15 months of treatment. After 53 months, the dog currently has stable disease, normal liver enzymes, CBC Analysis, and no evidence of toxicity. Clinical Significance: The use of vitamin B12 to deliver nitric oxide to tumors is novel. 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 partial 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. Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1771.

  • Phase I and pharmacokinetic study of sodium trans-[tetrachlorobis(1H-indazole)ruthenate(III)] / indazolehydrochloride (1:1.1) (FFC14A, KP1019) in patients with solid tumors – a study of the CESAR Central European Society for Anticancer Drug Research
    Cancer Research, 2005
    Co-Authors: Joseph A. Bauer, Bei H. Morrison, Zhuo Tang, Rhonda K. Oates, Joseph A. Lupica, Christine R. Anderson, Jean M. Poulson, Jennifer Gieg, Ernest C Borden, Daniel J. Lindner
    Abstract:

    471 Introduction: We evaluated the anti-neoplastic effects of nitrosylcobalamin (NO-Cbl) an apoptosis-inducing, vitamin B12 based carrier of nitric oxide (NO) in two dogs: 1.) a ten year old male Bichon Frise with aggressive Anal Sac Adenocarcinoma previously treated with adriamycin/radiation therapy and 2.) a 13 year old female Giant Schnauzer with parathyroid Adenocarcinoma previously treated with intra-tumor ethanol injection. Methods: Both dogs were given NO-Cbl 28 mg/kg/day s.c. which was increased to 42 mg/kg/day divided into two or three doses per day .Tumor regression was measured by physical exam and verified using CT, ultrasound and MRI. Summary of Data: After 15 weeks of daily NO-Cbl treatment, the male Bichon demonstrated a 50% regression in tumor volume based on physical exam and MR studies. No adverse side effects were noted as evidenced by normal liver enzyme levels, CBC Analysis, and normal creatinine levels, however BUN was elevated 3 times normal which may be a result of increased nitrate levels, a metabolite of NO-Cbl. After 10 weeks of NO-Cbl treatment, the female Giant Schnauzer demonstrated a 77% reduction in tumor volume, verified by ultrasound. Interestingly, she displayed normal blood chemistry (including BUN) and cell counts. Conclusion: The use of vitamin B12 to deliver nitric oxide to tumors is novel. We have shown previously that NO-Cbl is endocytosed by malignant cells resulting in intra-tumoral NO release. In this study, we show that daily long-term administration of NO-Cbl was effective in achieving partial responses in two canines with spontaneous tumors. Importantly, both dogs tolerated treatment extremely well, maintained normal blood chemistry, and showed no evidence of bone marrow suppression. The use of NO-Cbl capitalizes on the tumor specific properties of the vitamin B12 receptor (transcobalamin II, TCII receptor) expression and represents a promising anti-cancer therapy.

Jennifer Gieg – One of the best experts on this subject based on the ideXlab platform.

  • Anti-tumor effects of nitrosylcobalamin against spontaneous tumors in dogs
    Investigational New Drugs, 2010
    Co-Authors: Joseph A. Bauer, Jennifer Gieg, Gerald Frye, Anne Bahr, Peter Brofman
    Abstract:

    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.

  • Abstract #1771: Anti-tumor effects of nitrosylcobalamin (NO-Cbl) against spontaneous tumors in dogs
    Cancer Research, 2009
    Co-Authors: Joseph A. Bauer, Jennifer Gieg, Gerald Frye, Anne Bahr, Daniel J. Lindner
    Abstract:

    Background: Given the limited options available to treat canine cancers, the use of companion animals (pets) for evaluating new drugs may identify better therapies for veterinary and human oncology. Objective: The anti-tumor effects of nitrosylcobalamin (NO-Cbl), an apoptosis-inducing, vitamin B12 based carrier of nitric oxide (NO), was evaluated in three dogs with spontaneous carcinomas. Animals: (1) A 13 year-old female spayed Giant Schnauzer was diagnosed with inoperable thyroid carcinoma and hypercalcemia. (2) A 6 yr-old male neutered Golden Retriever presented malignant peripheral nerve sheath tumor (MPNST). (3) A ten yr-old castrated male Bichon Frise presented with apocrine gland Anal Sac Adenocarcinoma (AGACA) after previously failing multiple therapies. Methods: The dogs were administered single agent NO-Cbl 28 mg/kg s.c. b.i.d. In addition the Bichon Frise received 6 cycles of carboplatin during week 42 – 56 of treatment. Tumor regression was measured by physical exam and verified using ultrasound and MRI. Serum chemistries and hematologic parameters were monitored throughout the studies. Results: (1) The Giant Schnauzer demonstrated a 77% reduction in tumor volume compared to baseline after ten months of daily NO-Cbl treatment. (2) The Golden Retriever demonstrated a 39% reduction in tumor volume compared to pre-treatment after 9 months of daily NO-Cbl therapy. (3) The Bichon Frise demonstrated a 43% regression of the primary tumor and a 90% regression of the iliac lymph node measured by MRI after 15 months of treatment. After 53 months, the dog currently has stable disease, normal liver enzymes, CBC Analysis, and no evidence of toxicity. Clinical Significance: The use of vitamin B12 to deliver nitric oxide to tumors is novel. 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 partial 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. Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1771.

  • Phase I and pharmacokinetic study of sodium trans-[tetrachlorobis(1H-indazole)ruthenate(III)] / indazolehydrochloride (1:1.1) (FFC14A, KP1019) in patients with solid tumors – a study of the CESAR Central European Society for Anticancer Drug Research
    Cancer Research, 2005
    Co-Authors: Joseph A. Bauer, Bei H. Morrison, Zhuo Tang, Rhonda K. Oates, Joseph A. Lupica, Christine R. Anderson, Jean M. Poulson, Jennifer Gieg, Ernest C Borden, Daniel J. Lindner
    Abstract:

    471 Introduction: We evaluated the anti-neoplastic effects of nitrosylcobalamin (NO-Cbl) an apoptosis-inducing, vitamin B12 based carrier of nitric oxide (NO) in two dogs: 1.) a ten year old male Bichon Frise with aggressive Anal Sac Adenocarcinoma previously treated with adriamycin/radiation therapy and 2.) a 13 year old female Giant Schnauzer with parathyroid Adenocarcinoma previously treated with intra-tumor ethanol injection. Methods: Both dogs were given NO-Cbl 28 mg/kg/day s.c. which was increased to 42 mg/kg/day divided into two or three doses per day .Tumor regression was measured by physical exam and verified using CT, ultrasound and MRI. Summary of Data: After 15 weeks of daily NO-Cbl treatment, the male Bichon demonstrated a 50% regression in tumor volume based on physical exam and MR studies. No adverse side effects were noted as evidenced by normal liver enzyme levels, CBC Analysis, and normal creatinine levels, however BUN was elevated 3 times normal which may be a result of increased nitrate levels, a metabolite of NO-Cbl. After 10 weeks of NO-Cbl treatment, the female Giant Schnauzer demonstrated a 77% reduction in tumor volume, verified by ultrasound. Interestingly, she displayed normal blood chemistry (including BUN) and cell counts. Conclusion: The use of vitamin B12 to deliver nitric oxide to tumors is novel. We have shown previously that NO-Cbl is endocytosed by malignant cells resulting in intra-tumoral NO release. In this study, we show that daily long-term administration of NO-Cbl was effective in achieving partial responses in two canines with spontaneous tumors. Importantly, both dogs tolerated treatment extremely well, maintained normal blood chemistry, and showed no evidence of bone marrow suppression. The use of NO-Cbl capitalizes on the tumor specific properties of the vitamin B12 receptor (transcobalamin II, TCII receptor) expression and represents a promising anti-cancer therapy.

Christine R. Anderson – One of the best experts on this subject based on the ideXlab platform.

  • Phase I and pharmacokinetic study of sodium trans-[tetrachlorobis(1H-indazole)ruthenate(III)] / indazolehydrochloride (1:1.1) (FFC14A, KP1019) in patients with solid tumors – a study of the CESAR Central European Society for Anticancer Drug Research
    Cancer Research, 2005
    Co-Authors: Joseph A. Bauer, Bei H. Morrison, Zhuo Tang, Rhonda K. Oates, Joseph A. Lupica, Christine R. Anderson, Jean M. Poulson, Jennifer Gieg, Ernest C Borden, Daniel J. Lindner
    Abstract:

    471 Introduction: We evaluated the anti-neoplastic effects of nitrosylcobalamin (NO-Cbl) an apoptosis-inducing, vitamin B12 based carrier of nitric oxide (NO) in two dogs: 1.) a ten year old male Bichon Frise with aggressive Anal Sac Adenocarcinoma previously treated with adriamycin/radiation therapy and 2.) a 13 year old female Giant Schnauzer with parathyroid Adenocarcinoma previously treated with intra-tumor ethanol injection. Methods: Both dogs were given NO-Cbl 28 mg/kg/day s.c. which was increased to 42 mg/kg/day divided into two or three doses per day .Tumor regression was measured by physical exam and verified using CT, ultrasound and MRI. Summary of Data: After 15 weeks of daily NO-Cbl treatment, the male Bichon demonstrated a 50% regression in tumor volume based on physical exam and MR studies. No adverse side effects were noted as evidenced by normal liver enzyme levels, CBC Analysis, and normal creatinine levels, however BUN was elevated 3 times normal which may be a result of increased nitrate levels, a metabolite of NO-Cbl. After 10 weeks of NO-Cbl treatment, the female Giant Schnauzer demonstrated a 77% reduction in tumor volume, verified by ultrasound. Interestingly, she displayed normal blood chemistry (including BUN) and cell counts. Conclusion: The use of vitamin B12 to deliver nitric oxide to tumors is novel. We have shown previously that NO-Cbl is endocytosed by malignant cells resulting in intra-tumoral NO release. In this study, we show that daily long-term administration of NO-Cbl was effective in achieving partial responses in two canines with spontaneous tumors. Importantly, both dogs tolerated treatment extremely well, maintained normal blood chemistry, and showed no evidence of bone marrow suppression. The use of NO-Cbl capitalizes on the tumor specific properties of the vitamin B12 receptor (transcobalamin II, TCII receptor) expression and represents a promising anti-cancer therapy.

  • phase i and pharmacokinetic study of sodium trans tetrachlorobis 1h indazole ruthenate iii indazolehydrochloride 1 1 1 ffc14a kp1019 in patients with solid tumors a study of the cesar central european society for anticancer drug research ewiv
    Cancer Research, 2005
    Co-Authors: Joseph A. Bauer, Bei H. Morrison, Zhuo Tang, Rhonda K. Oates, Joseph A. Lupica, Christine R. Anderson, Jean M. Poulson, Jennifer Gieg, Ernest C Borden, Daniel J. Lindner
    Abstract:

    471 Introduction: We evaluated the anti-neoplastic effects of nitrosylcobalamin (NO-Cbl) an apoptosis-inducing, vitamin B12 based carrier of nitric oxide (NO) in two dogs: 1.) a ten year old male Bichon Frise with aggressive Anal Sac Adenocarcinoma previously treated with adriamycin/radiation therapy and 2.) a 13 year old female Giant Schnauzer with parathyroid Adenocarcinoma previously treated with intra-tumor ethanol injection. Methods: Both dogs were given NO-Cbl 28 mg/kg/day s.c. which was increased to 42 mg/kg/day divided into two or three doses per day .Tumor regression was measured by physical exam and verified using CT, ultrasound and MRI. Summary of Data: After 15 weeks of daily NO-Cbl treatment, the male Bichon demonstrated a 50% regression in tumor volume based on physical exam and MR studies. No adverse side effects were noted as evidenced by normal liver enzyme levels, CBC Analysis, and normal creatinine levels, however BUN was elevated 3 times normal which may be a result of increased nitrate levels, a metabolite of NO-Cbl. After 10 weeks of NO-Cbl treatment, the female Giant Schnauzer demonstrated a 77% reduction in tumor volume, verified by ultrasound. Interestingly, she displayed normal blood chemistry (including BUN) and cell counts. Conclusion: The use of vitamin B12 to deliver nitric oxide to tumors is novel. We have shown previously that NO-Cbl is endocytosed by malignant cells resulting in intra-tumoral NO release. In this study, we show that daily long-term administration of NO-Cbl was effective in achieving partial responses in two canines with spontaneous tumors. Importantly, both dogs tolerated treatment extremely well, maintained normal blood chemistry, and showed no evidence of bone marrow suppression. The use of NO-Cbl capitalizes on the tumor specific properties of the vitamin B12 receptor (transcobalamin II, TCII receptor) expression and represents a promising anti-cancer therapy.

Joseph A. Lupica – One of the best experts on this subject based on the ideXlab platform.

  • Phase I and pharmacokinetic study of sodium trans-[tetrachlorobis(1H-indazole)ruthenate(III)] / indazolehydrochloride (1:1.1) (FFC14A, KP1019) in patients with solid tumors – a study of the CESAR Central European Society for Anticancer Drug Research
    Cancer Research, 2005
    Co-Authors: Joseph A. Bauer, Bei H. Morrison, Zhuo Tang, Rhonda K. Oates, Joseph A. Lupica, Christine R. Anderson, Jean M. Poulson, Jennifer Gieg, Ernest C Borden, Daniel J. Lindner
    Abstract:

    471 Introduction: We evaluated the anti-neoplastic effects of nitrosylcobalamin (NO-Cbl) an apoptosis-inducing, vitamin B12 based carrier of nitric oxide (NO) in two dogs: 1.) a ten year old male Bichon Frise with aggressive Anal Sac Adenocarcinoma previously treated with adriamycin/radiation therapy and 2.) a 13 year old female Giant Schnauzer with parathyroid Adenocarcinoma previously treated with intra-tumor ethanol injection. Methods: Both dogs were given NO-Cbl 28 mg/kg/day s.c. which was increased to 42 mg/kg/day divided into two or three doses per day .Tumor regression was measured by physical exam and verified using CT, ultrasound and MRI. Summary of Data: After 15 weeks of daily NO-Cbl treatment, the male Bichon demonstrated a 50% regression in tumor volume based on physical exam and MR studies. No adverse side effects were noted as evidenced by normal liver enzyme levels, CBC Analysis, and normal creatinine levels, however BUN was elevated 3 times normal which may be a result of increased nitrate levels, a metabolite of NO-Cbl. After 10 weeks of NO-Cbl treatment, the female Giant Schnauzer demonstrated a 77% reduction in tumor volume, verified by ultrasound. Interestingly, she displayed normal blood chemistry (including BUN) and cell counts. Conclusion: The use of vitamin B12 to deliver nitric oxide to tumors is novel. We have shown previously that NO-Cbl is endocytosed by malignant cells resulting in intra-tumoral NO release. In this study, we show that daily long-term administration of NO-Cbl was effective in achieving partial responses in two canines with spontaneous tumors. Importantly, both dogs tolerated treatment extremely well, maintained normal blood chemistry, and showed no evidence of bone marrow suppression. The use of NO-Cbl capitalizes on the tumor specific properties of the vitamin B12 receptor (transcobalamin II, TCII receptor) expression and represents a promising anti-cancer therapy.

  • phase i and pharmacokinetic study of sodium trans tetrachlorobis 1h indazole ruthenate iii indazolehydrochloride 1 1 1 ffc14a kp1019 in patients with solid tumors a study of the cesar central european society for anticancer drug research ewiv
    Cancer Research, 2005
    Co-Authors: Joseph A. Bauer, Bei H. Morrison, Zhuo Tang, Rhonda K. Oates, Joseph A. Lupica, Christine R. Anderson, Jean M. Poulson, Jennifer Gieg, Ernest C Borden, Daniel J. Lindner
    Abstract:

    471 Introduction: We evaluated the anti-neoplastic effects of nitrosylcobalamin (NO-Cbl) an apoptosis-inducing, vitamin B12 based carrier of nitric oxide (NO) in two dogs: 1.) a ten year old male Bichon Frise with aggressive Anal Sac Adenocarcinoma previously treated with adriamycin/radiation therapy and 2.) a 13 year old female Giant Schnauzer with parathyroid Adenocarcinoma previously treated with intra-tumor ethanol injection. Methods: Both dogs were given NO-Cbl 28 mg/kg/day s.c. which was increased to 42 mg/kg/day divided into two or three doses per day .Tumor regression was measured by physical exam and verified using CT, ultrasound and MRI. Summary of Data: After 15 weeks of daily NO-Cbl treatment, the male Bichon demonstrated a 50% regression in tumor volume based on physical exam and MR studies. No adverse side effects were noted as evidenced by normal liver enzyme levels, CBC Analysis, and normal creatinine levels, however BUN was elevated 3 times normal which may be a result of increased nitrate levels, a metabolite of NO-Cbl. After 10 weeks of NO-Cbl treatment, the female Giant Schnauzer demonstrated a 77% reduction in tumor volume, verified by ultrasound. Interestingly, she displayed normal blood chemistry (including BUN) and cell counts. Conclusion: The use of vitamin B12 to deliver nitric oxide to tumors is novel. We have shown previously that NO-Cbl is endocytosed by malignant cells resulting in intra-tumoral NO release. In this study, we show that daily long-term administration of NO-Cbl was effective in achieving partial responses in two canines with spontaneous tumors. Importantly, both dogs tolerated treatment extremely well, maintained normal blood chemistry, and showed no evidence of bone marrow suppression. The use of NO-Cbl capitalizes on the tumor specific properties of the vitamin B12 receptor (transcobalamin II, TCII receptor) expression and represents a promising anti-cancer therapy.