Survival Time Of Tumor-bearing Animals Research Articles

Selective Induction of Melanomas in Gerbils (<italic>Meriones unguiculatus</italic>) Following Postnatal Administration of <italic>N</italic>-Ethyl-<italic>N</italic>-nitrosourea<xref ref-type="fn" rid="FN2">2</xref>

Following a single ip injection (50 mg/kg) of N-ethyl-N-nitrosourea (ENU) on postnatal day 7 or 20, 9 of 21 gerbils (43%) developed a total of 15 cutaneous melanomas. The mean survival time of tumor-bearing animals was 909 +/- 212 (SD) days. Neoplasms were preferentially located at sites with little hair and with high content of pigment cells (feet, ears, tail, or snout). Histologic studies on newborn gerbils indicated that ENU-induced malignant transformation occurred in differentiated melanocytes rather than in precursor cells of the neural crest.

Chemotherapy of experimental transitional-cell carcinoma

Transitional-cell carcinoma of the bladder has been induced by chronic oral administration of N-[4-(5-nitro-2-uryl)-2-thiazolyl] formamide (FANFT) in C3H/He mice, and successfully transplanted in syngeneic animals. Evaluation of the effectiveness of several chemotherapeutic agents on this tumor indicated that cyclophosphamide and cis-diammine diehloroplatinum (CACP) significantly inhibited tumor growth and prolonged the median survival time of tumor-bearing animals. When administered before formation of palpable tumors, cyclophosphamide completely prevented growth of the implants in 100 per cent of animals; when administered after the growth of larger, palpable tumors, cyclophosphamide inhibited tumor growth in all animals and produced a “cure” in 45 per cent. Combination chemotherapy with cyclophosphamide and CACP was more effective than either drug used as a single agent. Adriamycin, daetinomycin, and mitomycin C administered individually exhibited limited activity while 5 fluorouracil, CCNU (1–2 choloroethyl-3-cyclohexyl-l-nitrosourea), BCNU (1,3-bus [2-chloroethyl]-1-nitrosourea), methrotrexate, and hydroxyurea were ineffective against this tumor. The consistent growth pattern, the histologic similarity to bladder cancer in human beings, and the successful propagation in syngeneic animals, make the FANFT-induced tumor a suitable model for chemotherapy of bladder carcinoma in human beings.

Antineoplastic activity of highly purified bacterial glutaminases.

SEVERAL lines of evidence motivated the treatment of neoplasms by glutaminase to cause glutamine deprivation. Certain tumour cells grown in tissue culture require glutamine at a level which is tenfold or greater than that of any other amino-acid1,2. Glutamine participates in a wide variety of metabolic reactions in mammalian cells3. It has been suggested that one of the important functions of glutamine in the metabolism of certain tumours may be as a direct precursor of glutamic acid, which can then furnish the carbon for the partial operation of the tricarboxylic acid cycle from α-ketoglutarate to oxaloacetate4. Compared with other tissues, certain tumour cells seem to operate at a marginal level of glutamine availability because of slow synthesis5 and rapid utilization4. The glutamine antagonists, azaserine and 6-diazo-5-oxonorleucine (DON) have been shown to possess moderate antineoplastic activity, which may be enhanced by L-asparaginase6–8. Greenberg et al.9 reported that a glutaminase-asparaginase preparation with a relatively high glutamine Km (7 × 10−3M) decreased the initial rate of growth of a number of tumours, including an Ehrlich ascites carcinoma, but caused no significant increase in the survival time of tumour-bearing animals. In this study, more intensive therapy with three extensively purified glutaminase preparations with considerably lower Km values resulted in marked inhibition of an Ehrlich ascites carcinoma and significant increases in the survival time of tumour-bearing animals.