methylcellulose and Neoplasm-Metastasis

The inhibitory effect of poly(A)poly(U) on the pulmonary metastasis of B16-F10 melanoma was examined in comparison with that of poly(I,C)-L,C and poly(I)poly(C). The correlation between interferon (IFN) level and antimetastatic effect was also investigated. Intraperitoneal injection of poly(A)poly(U) (50 mg/kg) into C57BL/6 mice 24 h before intravenous inoculation of B16-F10 melanoma (1 X 10(5] caused a significant decrease (p less than 0.01) in the number of pulmonary nodules 14 days after tumor challenge. But poly(I,C)-L,C (1 or 0.2 mg/kg) and poly(I)poly(C) (5 mg/kg or 1 mg/kg) did not. From the kinetic study of IFN levels induced by polyribonucleotides, poly(I,C)-L,C showed the most potent IFN-inducing activity, followed by poly(I)poly(C) and poly(A)poly(U), in this order. Plasma IFN reached a peak at 6 h and still continued to be detected at 24 h after intraperitoneal injection of the polyribonucleotides. Against B16-F10 melanoma, the cytotoxicity of spleen cells stimulated by poly(A)poly(U) (50 mg/kg) was significantly (p less than 0.05) higher than that of spleen cells stimulated by poly(I)poly(C) (5 mg/kg) both at 12 and 24 h after intraperitoneal injection of those agents. The above results that there is no correlation between the IFN levels induced by polyribonucleotides and their antimetastatic effect. More extensive study of poly(A)poly(U) might give more fruitful results, which will give valuable information for future clinical trials of this lowly toxic promising agent.

Topics: Animals; Antineoplastic Agents; Carboxymethylcellulose Sodium; Carrageenan; Cytotoxicity, Immunologic; Interferon Inducers; Interferons; Male; Melanoma, Experimental; Methylcellulose; Mice; Mice, Inbred C57BL; Neoplasm Metastasis; Poly A-U; Poly I-C; Polylysine

Topics: Adult; Aged; Breast Neoplasms; Carboxymethylcellulose Sodium; Drug Evaluation; Female; Humans; Interferon Inducers; Methylcellulose; Middle Aged; Neoplasm Metastasis; Poly I-C; Polylysine

The systemic administration of multiple, nontoxic doses of polyinosinic-polycytidylic acid and poly-L-lysine solubilized by carboxymethylcellulose [poly(I,C)-LC] eradicated established experimental and spontaneous pulmonary metastases. Optimal immunotherapy was schedule dependent, requiring three to five injections of poly(I,C)-LC per week for a minimum of 4 weeks; in addition, therapeutic efficiency was partially dosage independent. Immunotherapy by poly(I,C)-LC was found to be limited by tumor burden, although when combined with chemotherapy as a debulking regimen it resulted in increased survival with protocols in which poly(I,C)-LC alone was insufficient. These data suggest that the systemic administration of poly(I,C)-LC may provide a successful adjuvant therapeutic modality against cancer metastasis.

Topics: Adjuvants, Immunologic; Animals; Carboxymethylcellulose Sodium; Cyclophosphamide; Drug Administration Schedule; Immunotherapy; Interferon Inducers; Male; Methylcellulose; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Neoplasm Metastasis; Neoplasms, Experimental; Peptides; Poly I-C; Polylysine

The development of successful immunotherapeutic protocols requires new therapeutic strategies as well as the development of clinically predictive tumor models and protocols. A bell-shaped response curve is observed with many biological response modifiers (BRMs), not only for immunomodulation, but also for therapeutic activity. Although most BRMs, including poly(I,C)-LC, are toxic at high doses, the administration of nontoxic doses by an optimal protocol and route of injection results in significant therapeutic benefit and increased immunomodulation in tumor-bearing animals compared to the administration of a maximum tolerated dose (MTD). We suggest that Phase II clinical trials using an optimal immunomodulatory protocol may result in increased therapeutic activity compared to protocols based on the MTD.

Topics: Animals; Carboxymethylcellulose Sodium; Cell Line; Drug Administration Schedule; Immunotherapy; Interferon Inducers; Methylcellulose; Mice; Neoplasm Metastasis; Neoplasms, Experimental; Poly I-C; Polylysine

Topics: Animals; Carcinoma, Ehrlich Tumor; Female; Injections, Intraperitoneal; Injections, Intravenous; Kidney Neoplasms; Liver Neoplasms; Lung Neoplasms; Methylcellulose; Mice; Neoplasm Metastasis; Polysaccharides; Resins, Plant; Sarcoma 180; Time Factors