Disease relevance of MOPIDAMOL

• RA-233 treatment was associated with a statistically significant prolongation of survival in patients with non-small cell lung cancer (N-SCLC) limited to one hemithorax and with reduction in mean plasma fibrogen concentration [1].
• RA-233 plus chemotherapy was compared with chemotherapy alone in a 5-year double-blind trial involving 719 patients with advanced carcinomas of the lung and of the colon [1].
• We investigated the in vitro effects of RA 233 on clones MTLn3 and MTC of differing metastatic potentials, isolated from the 13762NF rat mammary adenocarcinoma [2].
• RA 233, a pyrimido-pyrimidine analogue developed originally as an antiplatelet agent, has reduced the incidence of tumor metastases in clinical trials [3].
• Pretreatment with a platelet inhibitor, RA-233, abolished the formation of platelet thrombi and remarkably enhanced the leakage of edema fluid [4].

High impact information on MOPIDAMOL

• In contrast, clonal heterogeneity in drug-induced morphological changes, such as vacuole formation and altered organization of cytoskeletal structures, as well as increased tumor cell growth at 50 microM RA 233 was observed between clones MTLn3 and MTC [2].
• The growth of MTC cells (low spontaneous metastatic potential) was not affected by low concentrations of RA 233 (50 microM) or epidermal growth factor (EGF) (up to 10 ng/ml) for 3 days in 0.5-10% fetal bovine serum [3].
• In addition, incubation of MTLn3 cells with 50 microM RA 233 resulted in an increase of p21ras protein expression, whereas there was no effect on the level of p21ras in identically treated MTC cells or when either clone was treated with 10 ng/ml EGF [3].
• All the PST measured after 3 months of treatment were within normal ranges and not different between placebo, dipyridamole or RA 233 treated subjects: averages in days were, respectively, 7.49, 7.11 and 6.88 [5].
• However, in platelet-rich plasma (PRP), RA 233 potentiated strongly Ado-mediated inhibition, whereas dipyridamole, dilazep and NBMPR were without activity [6].

Chemical compound and disease context of MOPIDAMOL

• This study suggests that the combination of dipyridamole and RA-233 provides an effective intervention for the antithrombotic approach to the treatment of cancer metastases [7].
• Previous studies suggested that RA 233 and RX-RA 85 increase cAMP levels in 2 other cell clones of rat 13762NF mammary adenocarcinoma by inhibiting phosphodiesterases [8].

Biological context of MOPIDAMOL

• In contrast, MTLn3 (high spontaneous metastatic potential) cell cultures maintained for 3 days in low (0.5-1%) serum in the presence of 1.25-10 ng/ml EGF doubled in cell numbers compared with control cultures, and addition of 50 microM RA 233 abrogated the growth-stimulatory effect of EGF [3].
• Relationship between glycolysis and proliferation of L 1210 cells in vitro: effect of a new pharmacological effector: RA-233 [9].
• The inhibitory effect of dipyridamole (RA 8) and its two derivatives (RA 233 andSH 869) on platelet aggregation in platelet-rich plasma (PRP) AND IN SUSPENSIONSOF WASHED PLATELETS WAS EVALUATED USING 3 AGGRESSING STIMULI: ADP, thrombin, and collagen [10].
• RA-233 had no effect on osmotic fragility of SS-genotype red blood cells [11].
• The intravenous administration of the inhibitor of platelet adhesiveness RA 233 to blood donors before and during cell separation did not increase the yield of platelets in the final concentrate [12].

Anatomical context of MOPIDAMOL

• We have explored the interaction of human fibroblastic beta interferon (HFIF) with a cAMP decomposition inhibitory pyrimido-pyrimidine derivative, Mopidamole (RA-233) in cultures of neoplastic and normal cell lines [13].
• The pyrimido-pyrimidine analogue RA 233 has pleiotropic and differential effects on cultured tumor cell clones isolated from the 13762NF rat mammary adenocarcinoma [14].
• In contrast, a drug-responsive clone of high metastatic potential (MTLn3) was rendered less invasive and its cell fragility was decreased with RA 233 treatment, although its adhesiveness to lung microvascular endothelial cells and subendothelial matrix was unaffected by RA 233 [14].
• Effect of RA-233 on erythrocytes from patients with eczema [15].
• The use of RA 233 in the preparation of platelets, with the blood cell separator [12].

Associations of MOPIDAMOL with other chemical compounds

• Treatment of MTF7 cells with RA 233 or RX-RA 85 enhanced microtubular organization concomitant with a decrease in microfilament organization [8].
• Two pyrimido-pyrimidine derivatives (RA 233 and VK 744) were found effective aggregation inhibitors in vitro of human and monkey platelets and in vivo in stumptailed monkeys and chimpanzees [16].

Gene context of MOPIDAMOL

• Unlike with human fibroblast interferon, we could not show a synergistic inhibitory effect between RA 233 and any of the six different interferons on these two human epithelial tumor cell lines [17].

Analytical, diagnostic and therapeutic context of MOPIDAMOL

• In tumor metastasis experiments, reductions of approximately 70% in hepatic nodules and 90% in surface area occupied by the tumor were seen with the combination treatment (dipyridamole plus RA-233) as compared with the control group of mice [7].
• Although RA 233 effectively inhibited the formation of spontaneous metastases, oral administration of RA233 prior to and after the intravenous inoculation of 1 X 10(5) B16F10 murine melanoma cells failed to inhibit subsequent lung colony formation [18].

References