Injection of 200 mg/kg of body weight of WR-2721 30 minutes before graded doses of cis-dichlorodi... more Injection of 200 mg/kg of body weight of WR-2721 30 minutes before graded doses of cis-dichlorodiammineplatinum(II) (cisplatin) increased the resistance of Fischer 344 rats to cisplatin-induced nephrotoxicity by a factor of 1.7, but did not alter the sensitivity of three different transplanted tumors to cisplatin-induced growth delay. As a consequence, it was possible to administer doses of cisplatin which would have been lethal in the absence of WR-2721 injection, resulting in a proportionally greater tumor response. WR-2721 can, therefore, increase the effectiveness of cisplatin therapy through selective protection against the toxic side effects of chemotherapy.
Injection of 200 mg/kg of body weight of WR-2721 30 minutes before graded doses of cis-dichlorodi... more Injection of 200 mg/kg of body weight of WR-2721 30 minutes before graded doses of cis-dichlorodiammineplatinum(II) (cisplatin) increased the resistance of Fischer 344 rats to cisplatin-induced nephrotoxicity by a factor of 1.7, but did not alter the sensitivity of three different transplanted tumors to cisplatin-induced growth delay. As a consequence, it was possible to administer doses of cisplatin which would have been lethal in the absence of WR-2721 injection, resulting in a proportionally greater tumor response. WR-2721 can, therefore, increase the effectiveness of cisplatin therapy through selective protection against the toxic side effects of chemotherapy.
This report summarizes the present status of the proposed use of WR-2721 (S-2-(3-aminopropylamino... more This report summarizes the present status of the proposed use of WR-2721 (S-2-(3-aminopropylamino)-ethylphosphorothioic acid) acid) in radiotherapy and/or chemotherapy. This drug selectively concentrates in normal tissues, both in vivo and in vitro, but is passively absorbed by virtually all of the solid tumors which have been studied. In vivo this drug can increase the resistance to radiation or alkylating agents (nitrogen mustard, cis-platinum, cyclophosphamide, and L-phenylalamine mustard) by factors of up to 3, while leaving the solid tumors to suffer the full effects of either treatment.
The concentration of histamine in blood was determined in 22 patients with solid malignant tumors... more The concentration of histamine in blood was determined in 22 patients with solid malignant tumors, 16 hospitalized non-cancer patients and 9 healthy subjects. Patients with cancer (mainly carcinomas of the breast and gastrointestinal tract) were divided into two groups: patients with resected primary tumor without known metastases (group I) and patients with present primary tumor with or without metastases (group II). In comparison with the healthy subjects (histamine concentration 69.0 +/- 6.03 ng.ml-1), cancer patients in both groups had significantly decreased levels of histamine in blood. Also, the concentration of histamine in patients with present tumor (group II; 40.1 +/- 3.48 ng.ml-1) vas significantly lower than in patients with resected primary tumor (49.9 +/- 3.14 ng.ml-1). Furthermore, hospitalized non-cancer patients had lower, but not statistically significant, concentration of histamine (59.7 +/- 6.13 ng.ml-1) than healthy subjects. These findings, together with similar data of other authors, suggest that decreased level of histamine in blood might be a good nonspecific marker for onset and progression of solid malignant tumors.
Injection of 200 mg/kg of body weight of WR-2721 30 minutes before graded doses of cis-dichlorodi... more Injection of 200 mg/kg of body weight of WR-2721 30 minutes before graded doses of cis-dichlorodiammineplatinum(II) (cisplatin) increased the resistance of Fischer 344 rats to cisplatin-induced nephrotoxicity by a factor of 1.7, but did not alter the sensitivity of three different transplanted tumors to cisplatin-induced growth delay. As a consequence, it was possible to administer doses of cisplatin which would have been lethal in the absence of WR-2721 injection, resulting in a proportionally greater tumor response. WR-2721 can, therefore, increase the effectiveness of cisplatin therapy through selective protection against the toxic side effects of chemotherapy.
Injection of 200 mg/kg of body weight of WR-2721 30 minutes before graded doses of cis-dichlorodi... more Injection of 200 mg/kg of body weight of WR-2721 30 minutes before graded doses of cis-dichlorodiammineplatinum(II) (cisplatin) increased the resistance of Fischer 344 rats to cisplatin-induced nephrotoxicity by a factor of 1.7, but did not alter the sensitivity of three different transplanted tumors to cisplatin-induced growth delay. As a consequence, it was possible to administer doses of cisplatin which would have been lethal in the absence of WR-2721 injection, resulting in a proportionally greater tumor response. WR-2721 can, therefore, increase the effectiveness of cisplatin therapy through selective protection against the toxic side effects of chemotherapy.
This report summarizes the present status of the proposed use of WR-2721 (S-2-(3-aminopropylamino... more This report summarizes the present status of the proposed use of WR-2721 (S-2-(3-aminopropylamino)-ethylphosphorothioic acid) acid) in radiotherapy and/or chemotherapy. This drug selectively concentrates in normal tissues, both in vivo and in vitro, but is passively absorbed by virtually all of the solid tumors which have been studied. In vivo this drug can increase the resistance to radiation or alkylating agents (nitrogen mustard, cis-platinum, cyclophosphamide, and L-phenylalamine mustard) by factors of up to 3, while leaving the solid tumors to suffer the full effects of either treatment.
The concentration of histamine in blood was determined in 22 patients with solid malignant tumors... more The concentration of histamine in blood was determined in 22 patients with solid malignant tumors, 16 hospitalized non-cancer patients and 9 healthy subjects. Patients with cancer (mainly carcinomas of the breast and gastrointestinal tract) were divided into two groups: patients with resected primary tumor without known metastases (group I) and patients with present primary tumor with or without metastases (group II). In comparison with the healthy subjects (histamine concentration 69.0 +/- 6.03 ng.ml-1), cancer patients in both groups had significantly decreased levels of histamine in blood. Also, the concentration of histamine in patients with present tumor (group II; 40.1 +/- 3.48 ng.ml-1) vas significantly lower than in patients with resected primary tumor (49.9 +/- 3.14 ng.ml-1). Furthermore, hospitalized non-cancer patients had lower, but not statistically significant, concentration of histamine (59.7 +/- 6.13 ng.ml-1) than healthy subjects. These findings, together with similar data of other authors, suggest that decreased level of histamine in blood might be a good nonspecific marker for onset and progression of solid malignant tumors.
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