Hemoglobin II immunogenic properties of stroma vs. stroma‐free hemoglobin solution

Cochin, A; Gupta, Tapas K. Das; DeWoskin, R; Moss, Gerald S.

doi:10.1002/jso.2930060104

Cited by 14 publications

(3 citation statements)

References 8 publications

(8 reference statements)

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“…In addition, in contrast to human hemoglobin, bovine hemoglobin has low concentrations of organic phosphates [38], and has more pronounced Haldane (CO,) and Bohr (pH) effects [33]. Ultrapurified bovine hemoglobin has been shown in preclinical studies to have low antigenicity among mammals [35,36].…”

Section: Introductionmentioning

confidence: 99%

PEG-Hemoglobin:Effects on tumor oxygenation and radiosensitization

Teicher

Ara

Chen

et al. 1996

Radiat. Oncol. Investig.

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Derivatization with polyethylene glycol (PEG) is a biocompatible method to improve the therapeutic benefit of administered proteins by increasing their biological half‐life. The ability of a PEG‐bovine hemoglobin preparation (2–8 ml/kg) to increase the oxygen content of hypoxic tumor regions was determined in rats bearing the 13762 mammary carcinoma using an Eppendorf pO2 histograph. Administration of PEG‐hemoglobin decreased the percent of pO2 readings ≤ 5 mmHg in animals breathing air or breathing carbogen, respectively. In rats, PEG‐hemoglobin has a circulating half‐life of 20 hr. A single administration of PEG‐hemoglobin was able to provide increased tumor oxygenation on the following at least 3 days if atmospheres of 28% oxygen or carbogen were breathed. PEG‐hemoglobin administration along with fractionated radiation therapy (2, 3 or 4 Gy × 5) resulted in radiation dose modifying factors of 1.2 ± 0.2, 1.4 ± 0.2 and 1.5 ± 0.2 when the animals breathed air, 28% oxygen or carbogen prior to and during radiation delivery, respectively. Using the EMT‐6 murine mammary carcinoma tumor cell survival assay, administration of PEG‐hemoglobin (6 ml/kg) prior to single dose radiation therapy resulted in dose modifying factors of 1.4 ± 0.2 1.8 ± 0.2 and 1.9 ± 0.2 when the animals breathed air, 28% oxygen or carbogen prior to and during radiation delivery, respectively. In EMT‐6 tumor growth delay, administration of PEG‐hemoglobin (6 ml/kg) along with fractionated radiation therapy (2, 3 or 4 Gy × 5) resulted in dose modifying factors of 1.2 ± 0.2, 1.5 ± 0.2 and 1.7 ± 0.2 when the animals breathed air, 28% oxygen or carbogen prior to and during radiation delivery. Administration of PEG‐hemoglobin only on the first treatment day of a 5‐day fractionated radiation therapy regimen resulted in dose modifying factors of 1.3 ± 0.2 and 1.4 ± 0.2 if the animals breathed 28% oxygen or carbogen prior to and during each radiation fraction delivery. Further investigation of this potentially clinically important oxygen delivery agent is warranted. Radiat. Oncol. Invest. 4:200–210, 1996. © 1997 Wiley‐Liss, Inc.

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Section: Introductionmentioning

confidence: 99%

PEG-Hemoglobin:Effects on tumor oxygenation and radiosensitization

Teicher

Ara

Chen

et al. 1996

Radiat. Oncol. Investig.

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“…The results of this study support the conclusion that in human breast carcinoma, oxygcn tension distribution is a critical modifier of radiation treatment response [ Okunieff et al, 19931. Bovine blood is a ready source of hemoglobin [Breepel et al, 1981;Bunn, 1971;Cochen et al, 1974;Cunnington et al, 19811 Bohr (pH) effects [Breepel et al, 19811. Ultrapurified bovine hemoglobin has been shown in prcclinical stiidies to have low antigenicity ainong mammals [Cochen ct al., 1974;Cunnington et al, 19811. The ultrapurified polymerized bovine hemoglobin solution used in the current stiidies when administered intravenously to C3H mice bearing the FSaIIC fibrosarcoma has been shown to increase both the tumor growth delay and tumor cell killing by radiation therapy and by a variety of cheniotherapcutic agents with little increase in the toxicity of these agents to the bone inarrow [Teicher et al, 1992b,c].…”

Section: Discussionmentioning

confidence: 99%

Administration of a hemoglobin solution decreases hypoxia and increases radiation response in a rat mammary carcinoma

Teicher

Dupuis

Liu

et al. 1995

Drug Development Research

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Administration of an ultrapurified bovine hemoglobin solution (8 ml/kg, iv) to female Fisher 344 rats bearing the 13672 mammary carcinoma implanted subcutaneously in the hind leg reduced the hypoxic fraction of the tumor from 49 to 36% with normal air breathing and to 28% with carbogen (95% oxygen/5% carbon dioxide) breathing. When administration of the hemoglobin solution was followed by single dose (10,20, or 30 Gray) local radiation therapy, the dose modifying factor was 1.5 with air breathing and 2.7 with carbogen breathing. For fractionated radiation therapy, 2, 3, or 4 Gray was delivered locally daily for 5 days. When the hemoglobin solution was administered prior to each radiation fraction and air breathing maintained, there was a 1.8-fold increase in tumor growth delay. When daily hemoglobin solution administration was accompanied by carbogen breathing, there was a 2.6-fold increase in tumor growth delay. Less frquent administration of the hemoglobin solution (alternate days, twice weekly or once weekly) resulted in 1.5-to 1.7-fold increases in tumor growth delay. The greatest increases in tumor oxygenation occurred shortly after administration of the hemoglobin solution; in fact at 12 h post administration of the hemoglobin solution, the tumors appeared to be more hypoxic than prior to administration of the hemoglobin solution. by 24 h post administration of the hemoglobin solution, the oxygen tension profile of the tumors were returning to pretreatment levels. Further investigation of this ultrapurified hemoglobin solution in cancer is warranted.G 1995 Wiley-Liss, Inc.

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“…Moss et al (1973) recently reported further refinement of this solution by the elimination of a coagulant factor. At present, although antigenicity studies (Cochin et al, 1972) need elaboration, the most significant deficiency of this solution is the short biologic half-life resulting from rapid renal clearance. Clearance studies in animals (Relihan et al, 1972) demonstrated that 60% of hemoglobin was excreted in the urine during the first six hours following infusion.…”

Section: Discussionmentioning

confidence: 99%

Experimental use of heterologous stroma‐free hemoglobin solution (SFHS) as a whole blood substitute

Holdefer

Dowling

1974

Journal of Surgical Oncology

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Normothermic extracorporeal oxygenation and oxygen-hemoglobin dissociation characteristics of stroma-free hemoglobin solution (SFHS) were studied. One hour of normothermic cardiopulmonary bypass, using a total SFHS prime, resulted in arterial pH 7.31 ~ 7.38, PaO, 120 -140 mm Hg, SaO, 99%, and mean arterial pressure of 85 mm Hg. One hour after perfusion, the animal died with acute pulmonary edema from severe hemodilution and hypoxemia. Hypothermic (25OC) myocardial metabolism was studied. Myocardial utilization (MU) values for oxygen, lactate, pyruvate, and glucose during SFHS perfusion were 1.46 and 1.71 m1/100 gm/min, +1.01 and +0.08 mg/100 gm/min, -0.32 and -0.04 mg/100 gm/min, and -34.4 and -9.50 mg/100 gm/min. MU values during whole blood perfusion were 2.21 and 2.13 m1/100 gm/min, -5.19 and -2.99 mg/100 gm/min, -0.65 and 0.22 mg/100 gm/min, and -13.7 and -5.32 mg/100 gm/min. These data suggest the necessity of further studies t o identify any usefulness of SFHS as a whole blood substitute.

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Hemoglobin II immunogenic properties of stroma vs. stroma‐free hemoglobin solution

Cited by 14 publications

References 8 publications

PEG-Hemoglobin:Effects on tumor oxygenation and radiosensitization

PEG-Hemoglobin:Effects on tumor oxygenation and radiosensitization

Administration of a hemoglobin solution decreases hypoxia and increases radiation response in a rat mammary carcinoma

Experimental use of heterologous stroma‐free hemoglobin solution (SFHS) as a whole blood substitute

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