Inhibitory effect of bombesin/gastrin-releasing peptide (GRP) antagonists RC-3950-II and RC-3095 on MCF-7 MIII human breast cancer xenografts in nude mice

Gastrin-releasing peptide (GRP) induces angiogenesis and the specific GRP blocker 77427 inhibits tumor growth in vitro and in vivo

“…Secondly, this behavior has been previously described for other antiangiogenic drugs (Soffer et al, 2001), stressing the need to develop combination therapies including a cytotoxic agent and an antiangiogenic substance (Los and Voest, 2001;Wachsberger et al, 2003). Other small molecules that inhibit GRP activity have been shown to be efficient in reducing tumor growth in vivo (Shirahige et al, 1994;Moody et al, 1996b;Damge and Hajri, 1998). In view of our results, it would be interesting to investigate whether angiogenesis blockade is also part of their mechanism of action.…”

Design, synthesis, and in vitro evaluation of cytotoxic analogs of bombesin-like peptides containing doxorubicin or its intensely potent derivative, 2-pyrrolinodoxorubicin

“…Accordingly, receptors for BN-like peptides are present on normal, nonmalignant cells in the digestive tract, the central nervous system and other target organs such as the lung (1, 2, 10). Investigation of the role of BN-like peptides in the mitogenesis of various cancers revealed that high-affinity binding sites for these peptide hormones are also expressed on a wide variety of human and experimental animal tumors (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32). A recent study also indicates that on certain cancers, such as azaserine-induced pancreatic carcinoma in the rat, highaffinity GRP receptors are present in significantly higher numbers than on the normal pancreas (38).…”

“…Antitumoral effects of BN͞GRP antagonists in vivo have been demonstrated on CFPAC-1 and SW-1990 human pancreatic cancers (17,18), nitrosamine-induced pancreatic cancers in hamsters (19), H69 human SCLC (20), MKN45 and Hs746T human gastric cancers (21,22), HT-29 human colon cancers (23,24), PC-82, PC-3, and DU-145 human prostate cancers (25,26), androgen independent Dunning R-3327-AT-1 rat prostate cancers (27), estrogen dependent and independent MXT mouse mammary cancers (28), MCF-7 MIII human breast cancer (29), and U-87MG and U-373MG human glioblastomas (30). Receptor analyses of these tumors showed the presence of high-affinity binding sites for 125 I[Tyr 4 ]BN (1,2,(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33). Recently, we described the synthesis and evaluation of cytotoxic analogs of luteinizing hormone-releasing hormone containing doxorubicin (DOX) or 2-pyrrolino-DOX, a derivative 500-1000 times more potent (34,35).…”

“…These cytotoxic analogs were developed for therapy of cancers that contain receptors for luteinizing hormone-releasing hormone (35). The presence of receptors for BN-like peptides on a wide variety of tumors (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33), prompted us to use some of our powerful BN͞GRP antagonists as carrier molecules for targeting cytotoxic agents to tumor cells.…”

Correlation between the effects of bombesin antagonists on cell proliferation and intracellular calcium concentration in Swiss 3T3 and HT-29 cell lines.

“…These modern bombesin/GRP antagonists have also been tested for their ability to inhibit growth of MCF-7 MIII human breast cancers (16), nitrosamineinduced pancreatic cancer in hamsters (17,18), MXT mammary cancer in mice (19), HT-29 human colon cancer (20), PC-82 human prostate cancer (21), and Hs746T human gastric cancer (22).…”