bropirimine and Adenocarcinoma

The role of bropirimine in prostate cancer remains unexplored. To address the efficacy of this immune modulator as neoadjuvant therapy we utilized the orthotopic placement of the Dunning AT-3 tumor. 2.4-2.6 x 10(6) Dunning AT-3 cells were injected into the ventral prostates of 50 Copenhagen X Fischer rats. Animals were then divided into 5 groups consisting of: 1) untreated controls; 2) those treated with ventral prostatectomy alone (performed 10-12 days following tumor cell inoculation); 3) those treated with ventral prostatectomy plus bropirimine (10 mg/kg) on postimplantation days 1, 3, 5, 10 and 11; 4) those treated with ventral prostatectomy plus bropirimine (100 mg/kg), at the same schedule; and 5) those treated with ventral prostatectomy plus bropirimine (500 mg/kg), at the same schedule. Animals were sacrificed 10 days after prostatectomy, autopsied, and residual disease was weighed. Prostate weights upon removal following neoadjuvant treatment and residual disease remaining after 20-22 days were expressed in grams (g). Following prostatectomy, mean prostate weights were: Group 2, 0.67 +/- 0.11; Group 3, 0.53 +/- 0.11; Group 4, 0.54 +/- 0.12; Group 5, 0.44 +/- 0.09. The effect of bropirimine was significant (p = 0.0001) by multiple regression analysis. In addition, mean residual tumor weights (expressed in grams) after 20-22 days were: Group 1, 12.7 +/- 1.9; Group 2, 6.7 +/- 4.8; Group 3, 5.2 +/- 5.9; Group 4, 3.8 +/- 3.5; and Group 5, 2.8 +/- 3.5. The effect of bropirimine was not significant (p = 0.07) by multiple regression analysis. However, prostatectomy alone, by Student's test, significantly (p = 0.04) reduced residual mean tumor weights by 47% and the additional effect of bropirimine upon residual disease was significant (p = 0.038) if a Chi-square analysis is applied. Finally, a multivariate analysis of the overall effect of bropirimine in rats treated with prostatectomy was significant (p = 0.002). The effect of bropirimine on expression of proliferating cell nuclear antigen (PCNA) and transforming growth factor beta 1 (TGF-beta 1) was also evaluated immunohistochemically and expression of both tumor markers was significantly reduced (p < 0.05). We conclude that bropirimine may have a role as a neoadjuvant therapy when combined with prostatectomy.

Topics: Adenocarcinoma; Animals; Antineoplastic Agents; Biomarkers, Tumor; Cytosine; Down-Regulation; Gene Expression Regulation, Neoplastic; Injections, Intraperitoneal; Male; Neoplasm, Residual; Proliferating Cell Nuclear Antigen; Prostatic Neoplasms; Rats; Rats, Inbred F344; Transforming Growth Factor beta; Tumor Cells, Cultured

To evaluate bropirimine for in vivo activity in rodent prostate cancer.. Subcutaneously injected PAIII and Dunning MAT-LyLu rodent prostate cancer cells caused solid tumors and death in controls. Bropirimine was given on varying schedules at 250 mg./kg. by gavage, and tumor volume and survival were recorded.. Bropirimine prevented growth when given on the day of tumor injection and caused 95% of advanced tumors to regress completely in the PAIII model. Bropirimine caused significant growth inhibition and prolongation of survival in the MAT-LyLu model.. Bropirimine has statistically significant in vivo activity against both of these rodent prostate cancer cell lines.

Topics: Adenocarcinoma; Animals; Antineoplastic Agents; Cytosine; Male; Neoplasm Transplantation; Prostatic Neoplasms; Rats; Rats, Inbred Strains; Time Factors; Tumor Cells, Cultured

This investigation aimed to develop a biologically relevant murine model of colorectal liver metastases and determine if Kupffer cells (KC) and hepatic natural killer cells (hNKC) regulate tumor growth. The model involves the injection of murine colon adenocarcinoma 26 (MCA 26) tumor cells into the portal vein of female-specific pathogen-free BALB/c mice. Metastases developed in all animals, and the growth was limited entirely to the liver. To determine if KC and hNKC control the development of liver metastases, the in vivo function of these hepatic effector cells was modulated. Tumor growth was quantitated by the uptake of 125I into tumor DNA. Stimulation of the KC and hNKC produced a significant (P less than 0.01) dose-dependent decrease in 125I uptake in the liver in both treatment groups, which was associated with a significant improvement in survival (P less than 0.05). The in vivo cytotoxic function of the liver was inhibited with an intravenous injection of gadolinium chloride (for KC) or asialo GM1 antiserum (for hNKC). Inhibition of KC and hNKC cytotoxic function led to a significant (P less than 0.01) increase in 125I uptake in the liver and a significant decrease in survival (P less than 0.05).

Topics: Adenocarcinoma; Animals; Antineoplastic Agents; Cell Division; Cell Line; Cell Survival; Colonic Neoplasms; Cytosine; Cytotoxicity, Immunologic; Female; G(M1) Ganglioside; Gadolinium; Immune Sera; Killer Cells, Natural; Kupffer Cells; Liver Neoplasms; Mice; Mice, Inbred BALB C; Propionibacterium acnes; Rectal Neoplasms

It is well documented that the antitumor capacity of tumor necrosis factor (TNF) can be enhanced by interferons (IFNs), notably IFN-gamma. The aim of this study was to investigate the efficacy of a combined treatment with TNF and the IFN-inducer 2-amino-5-bromo-6-phenyl-4-pyrimidinone (ABPP) on a transplantable colon carcinoma (CC531) in rats. The tumor was implanted under the kidney capsule of syngeneic rats; the tumors were removed a week after implantation and growth was assessed by weighing. The animals were treated with 1 microgram of TNF, given i.v. on days 0, 2, and 4; and with 250 mg/kg of ABPP, administered i.p. on days 0 and 1. The results of two separate experiments indicated that both TNF and ABPP had a significant inhibitory effect on tumor growth. Combined, the two agents were found to act additively. In the dosage used, TNF toxicity was mild, transient, and not influenced by ABPP.

Topics: Adenocarcinoma; Animals; Antineoplastic Agents; Colonic Neoplasms; Cytosine; Drug Therapy, Combination; Interferon Inducers; Male; Rats; Rats, Inbred Strains; Tumor Necrosis Factor-alpha