Tumor response

Repeat CT scans of the chest after the first cycle of chemotherapy, surgical stenting, or radiotherapy to assess tumor response. 

Stoner GD, Shimkin MB, Troxell MC, et al. 1976. Test for carcinogenicity of metallic compounds by the pulmonary tumor response in strain A mice. Cancer Res 36 1744-1747. 

Dash wood RH, Arbogst DN, Fong AT, Pereira C, Hendricks JD and Baily GS. 1989. Quantitative interrelationships between aflatoxin B1 carcinogen dose, indole-3-carbinol anto-carcinogen dose, target organ DNA adduction and final tumor response. Carcinogenesis 10 175-181. 

Inhalation studies at the U.S. Air Force Aerospace Medical Research Laboratory showed an increased tumor response (hemangiosarcomas and Kupffer cell sarcomas) in mice exposed at 5 ppm, 6 h/d, 5 d/w for 6 mon (MacEwen and Vernot 1977, and Flaun 1977, reviewed in Trochimowicz 1994). Rats similarly exposed at 5 ppm exhibited increased incidences of squamous cell carcinomas of the lung and hepatocellular carcinomas. Hamsters subjected to a similar experimental protocol failed to show an increased incidence of tumors (MacEwen and Vernot 1975). It must be noted that the 1,1-dimethylhydrazine used in these studies contained 0.12% dimethylnitrosamine, which could be a significant confounder. 

Two oral studies in rodents demonstrated the carcinogenic potential of dimethylhydrazines. Results of an inhalation study in mice showing an increased tumor response following exposure to 1,1-dimethylhydrazine may be compromised by the contamination of the test article with dimethylnitrosamine. Both inhalation and oral slope factors for the dimethylhydrazines have been withdrawn from IRIS. 

Tumor response is measured by clinical chemistry (e.g., liver enzyme elevation in patients with hepatic metastases) or imaging techniques (e.g., bone scans or chest x-rays). 

The primary outcome to be identified is tumor response, which is based on physical examination, radiologic evidence, and other baseline findings. Complete response is desirable because it yields the only chance for cure. 

Fingar VH, Wieman TJ, Karavolos PS, Doak KW, Ouellet R, van Lier JE (1993) The effects of photodynamic therapy using differently substituted zinc phthalocyanines on vessel constriction, vessel leakage and tumor response. Photochem Photobiol 58 251-258. 

It is of more than a little interest to note that the sites of tumor formation do not always match across species. Benzidine, a substance once widely used in dye manufacture, was shown many years ago to be a carcinogenic risk for the bladder in workers exposed to excessive levels. The rat bladder is not responsive to this substance, but its liver is. It wasn t until Wilhelm Hueper turned to the dog that bladder cancer could be reproduced in a laboratory animal. It is now understood that benzidine metabolism is similar in dogs and people, and that metabolism in the rat takes a different course. It is also understood that certain benzidine metabolites, and not benzidine itself, are the proximate causes of tumors. Knowledge of metabolic differences helps explain the species similarities and differences in tumor response. If we had available the rat data and no human data, we would be in error to conclude that benzidine was a cause of human liver cancer. 

Many toxicologists are concerned about possible misinterpretation of bioassay results when the MTD (the highest bioassay dose) has turned out to produce serious toxicity as well as a tumor response. They contend that the excessive toxicity that somehow decreased... 

Where alternative approaches with signihcant biological support are available for the same tumor response and no scientihc consensus favors a single approach, an assessment may present results based on more than one approach. 

Squamous cell carcinomas of the skin were produced in three studies after skin application of benzotrichloride to mice. Lung carcinomas, pulmonary adenomas, and lymphomas were also observed, ftitraperitoneal injection of benzotrichloride produced a significant increase in the lung tumor response in strain A/f mice within 24 weeks. Administration by gastric intubation of doses ranging from 2.0 to... 

Mendel rats supports chronic renal tubule injury as the mode of action underlying the renal tumor response. Toxicol Set 53(2) 237-44, 2000... 

Poirier LA, Stoner GD, Shimkin MB Bioassay of alkyl halides and nucleotide base analogs by pulmonary tumor response in Strain A mice. Cancer Res 35(6) 1411-1415, 1975... 

Van Duuren BL, et al Carcinogenicity of epoxides, lactones, and peroxy compounds. IV. Tumor response in epithelial and connective tissue in mice and rats, f Natl Cancer Inst 37 825-834, 1966... 

In animal studies, significant increases in adenocarcinomas and squamous cell carcinomas of the lung have occurred in rats after inhalation or intratracheal instillation in rats, but not in hamsters. Increasing in vitro and in vivo evidence suggests that the rat lung tumor response to crystalline silica exposure is a result of marked and persistent inflammation and epithelial proliferation. However, other pathways such as a role for crystalline silica surfacegenerated oxidants or a direct genotoxic effect cannot be ruled out. 

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