Attila Nagy's research while affiliated with Tulane University and other places

Publications (69)

Article
Based on our previous results, in conjunction with various structural considerations, 19 new analogs of the GHRH antagonist [PhAc-Tyr1,D-Arg2,Phe(pCl)6,Abu15,Nle27,Agm29]hGHRH(1-29) (MZ-5-156) were synthesized by the solid-phase method. These compounds were designed to develop further analogs of this class with increased receptor-binding affinity....
Article
Malignant melanomas are characterized by a high intrinsic resistance to chemotherapy. Multiple drug resistance (MDR) can be mediated by transport proteins such as MDR-1, multidrug resistance-associated protein (MRP) or lung resistance protein (LRP). The cytotoxic analogue of somatostatin AN-238 consisting of 2-pyrrolinodoxorubicin (AN-201) linked t...
Article
Receptors for luteinizing hormone-releasing hormone (LHRH) on human prostate cancers can be used for targeted chemotherapy with cytotoxic analogs of LHRH, such as AN-207, which consists of superactive doxorubicin derivative 2-pyrrolino doxorubicin (AN-201) linked to carrier [D-Lys6] LHRH. The effects of AN-207 and AN-201 were investigated in DU-145...
Article
The cytotoxic analog of bombesin (BN)/gastrin releasing peptide (GRP) AN-215 consisting of 2-pyrrolinodoxorubicin (AN-201), a superactive derivative of doxorubicin linked to a bombesin analog carrier, displays a high affinity to BN/GRP receptors and can be targeted to tumors that express these receptors. We evaluated the antitumor effect and the to...
Article
We developed a powerful cytotoxic analogue of bombesin AN-215, in which the bombesin (BN)-like carrier peptide is conjugated to 2-pyrrolino doxorubicin (AN-201). Human prostate cancers express high levels of receptors for BN/gastrin releasing peptide (GRP) that can be used for targeted chemotherapy. The effects of targeted chemotherapy with cytotox...
Article
Targeted chemotherapy is a modern approach aimed at increasing the efficacy of systemic chemotherapy and reducing its side effects. The peptide receptors expressed primarily on cancerous cells can serve as targets for a selective destruction of malignant tumors. Binding sites for LHRH (now known in genome and microarray databases as GNRH1), were fo...
Article
Multidrug resistance (MDR) mediated by membrane transporters, such as P-glycoprotein (MDR-1) and MDR-associated protein (MRP), remains a challenge in the therapy of renal cell carcinoma (RCC). Chemotherapy targeted to hormone receptors may provide a new approach to overcome chemoresistance. The cytotoxic analogue of bombesin/gastrin-releasing pepti...
Article
Targeting anticancer agents to receptors for peptide hormones such as bombesin/gastrin-releasing peptide (GRP) on tumor cells increases the efficacy and lowers the toxicity of cancer therapy. We studied the expression of bombesin/GRP receptors in 6 experimental pancreatic cancers and evaluated tumor inhibition in vivo produced by targeted chemother...
Article
Chemoresistance mediated by membrane transporters such as multidrug resistance (MDR-1) glycoprotein remains a challenge in the chemotherapy treatment of advanced or recurrent endometrial carcinoma. Targeted chemotherapy might overcome this resistance. The cytotoxic somatostatin (SST) analog, AN-238, consists of a superactive derivative of doxorubic...
Article
We determined by immunohistochemistry the presence of LHRH receptors in surgical specimens of human non-Hodgkin's lymphomas (NHL) and investigated the expression of LHRH receptors in two human NHL cell lines, RL and HT by RT-PCR, Western blot and radioligand binding studies. In in vivo experiments with nude mice bearing tumours of these NHL cell li...
Article
In this study we have investigated the efficacy and toxicity of targeted cytotoxic bombesin (BN) analog AN-215 and its effects on the expression of three multidrug resistance proteins in experimental human endometrial cancers. Nude mice bearing HEC-1A, RL-95-2 and AN3CA tumours were treated with AN-215 and its cytotoxic radical (AN-201). The BN rec...
Article
To determine the expression of luteinizing hormone releasing hormone (LHRH) receptors in specimens and cell lines of human renal cell carcinoma (RCC) and to evaluate the antitumor efficacy of targeted therapy with a cytotoxic analogue of LHRH, AN-207, in vivo. AN-207, consisting of [D-Lys(6)] LHRH linked to a cytotoxic radical, 2-pyrrolinodoxorubic...
Article
Human gliomas express receptors for bombesin and somatostatin that can be used for targeted chemotherapy. In the present study, the efficacy and the mechanism of action of cytotoxic bombesin analog AN-215, and cytotoxic somatostatin analog AN-238 were investigated in U-118MG human glioblastomas xenografted into nude mice. The expression of vascular...
Article
Full-text available
Cytotoxic analogue of luteinizing hormone releasing hormone (LHRH), AN-207, binds with high affinity to LHRH receptors and can be targeted to tumors expressing these receptors. We investigated the expression of LHRH receptors in surgical specimens of human malignant melanoma and evaluated the effects of AN-207 in models of human melanoma. Human mel...
Article
To treat experimental human endometrial cancers based on targeted chemotherapy with the cytotoxic luteinizing hormone-releasing hormone (LHRH) analogues AN-152 and AN-207. Experimental study using athymic nude mice bearing xenografts of HEC-1A and RL-95-2 human endometrial cancers to assess the efficacy and toxicity of AN-152 and AN-207. The expres...
Article
The cytotoxic analogue of somatostatin, AN-238, consisting of 2-pyrrolinodoxorubicin (AN-201), a superactive derivative of doxorubicin (DOX), linked to somatostatin analogue carrier RC-121 binds with high affinity to receptors for somatostatin and can be targeted to tumors that express these receptors. Because somatostatin receptors are found in a...
Article
The efficacy of a targeted cytotoxic hybrid somatostatin analogue AN-238 and of its superactive radical 2-pyrrolinodoxorubicin (AN-201) to induce apoptosis of HepG2 and Hep3B human hepatoma cell lines were studied. AN-238 was designed to selectively target tumor cells expressing somatostatin receptor subtypes (sst(s)). Its effects on HepG2 or Hep3B...
Article
To determine whether the cytotoxic analogue of bombesin/gastrin-releasing peptide (GRP) AN-215 can inhibit the in vivo growth of four human ovarian cancer cell lines. AN-215 consists of 2-pyrrolinodoxorubicin (AN-201), a superactive derivative of doxorubicin linked to a bombesin antagonist carrier des-D-Tpi-RC-3095. This conjugate binds strongly to...
Article
More than 50% of human breast cancers express receptors for luteinizing hormone-releasing hormone (LHRH-R). These receptors can be used for targeted chemotherapy with agents like AN-152, in which doxorubicin is linked to analog [D-Lys6]LHRH. We compared the effects of AN-152 and doxorubicin in human breast cancer cells. MCF-7, T47D, HCC-70 and ZR-7...
Article
Objective: Eighty percent of human ovarian and endometrial cancers express receptors for luteinizing hormone-releasing hormone (LHRH-R). These receptors can be used for targeted chemotherapy with agents such as AN-152, in which doxorubicin is linked to analog [D-Lys(6)]-LHRH. Direct receptor-mediated antiproliferative effects of AN-152 have been s...
Article
Work on cytotoxic analogs of luteinizing hormone-releasing hormone (LH-RH), somatostatin and bombesin, designed for targeting chemotherapy to peptide receptors on various cancers, is reviewed here as the project is at advanced stages of development and clinical trials are pending. Cytotoxic analogs of LH-RH, AN-152 and AN-207, containing doxorubici...
Article
To improve conventional chemotherapy, we developed cytotoxic analogues of luteinizing hormone-releasing hormone (LH-RH), which can be targeted to prostate cancers expressing LH-RH receptors. In view of pending clinical trials on cytotoxic LH-RH analogue AN-152, containing doxorubicin (DOX) linked to [D-Lys(6])-LH-RH, we investigated the effects of...
Article
New modalities are necessary for the treatment of patients with unresectable gastric carcinoma. The authors investigated whether receptors for somatostatin and bombesin were present in human gastric carcinoma lines and tested the antitumor effects of cytotoxic somatostatin analog AN-238 and cytotoxic bombesin conjugate AN-215. Nude mice bearing AGS...
Article
The receptors for luteinizing hormone-releasing hormone receptor (LHRH-R) are found in >50% of human breast cancers. Doxorubicin (DOX) was linked to [D-Lys(6)]LHRH to form a cytotoxic conjugate, AN-152, which can be targeted to tumor cells expressing LHRH-R. We evaluated the effects of AN-152 on the estrogen-independent, DOX-resistant human mammary...
Article
The accumulation of radioactive somatostatin analog [111In]pentetreotide in non-small cell lung cancer (non-SCLC) during scintigraphy of patients provides a rationale for investigating the efficacy of somatostatin receptor-based chemotherapy in non-SCLC. Consequently, in this study, we evaluated the antitumor effects of cytotoxic somatostatin analo...
Article
Various peripheral human tissues express receptors for growth hormone secretagogue (GHS), the highest density being in the myocardium. It was also reported that some octapeptide analogs of somatostatin (SRIH) can displace radiolabeled Tyr-Ala-hexarelin from GHS receptors on the human pituitary and heart. Thus, it is possible that radionuclide analo...
Article
The development of targeted cytotoxic analogs of hypothalamic peptides for the therapy of various cancers is reviewed and various oncological studies on experimental tumors are summarized. Novel therapeutic modalities for breast, prostate and ovarian cancer consist of the use of targeted cytotoxic analogs of LH-RH containing doxorubicin (DOX) or 2-...
Article
A doxorubicin and [D-Lys(6)]Luteinizing Hormone-Releasing Hormone (LH-RH) conjugate, AN-152, was designed to target LH-RH receptor positive cells. AN-152 is more potent against a specific group of cancers than doxorubicin and has less peripheral toxicity. This therapy is potentially efficacious against many other types of malignancies. Here, AN-152...
Article
The receptors for luteinizing hormone-releasing hormone (LHRH) are found in 80% of human ovarian carcinomas. These receptors can be used for targeted chemotherapy with cytotoxic analogs of LHRH, such as AN-207, consisting of 2-pyrrolinodoxorubicin (AN-201) linked to [D-Lys ]LHRH. We investigated the effects of AN-207 and AN-201 on the growth of LHR...
Article
Most human endometrial and ovarian cancers express receptors for luteinizing hormone- releasing hormone. These receptors can be used for targeted chemotherapy with cytotoxic luteinizing hormone-releasing hormone analogs such as AN-152, in which doxorubicin is linked to [D-Lys(6)]luteinizing hormone-releasing hormone. The antitumor effects of doxoru...
Article
The resistance of advanced colorectal cancers to therapy is often related to mutations in the p53 tumor suppressor gene. Because somatostatin (SRIF) receptors (ssts) are present in colorectal carcinomas, the treatment with targeted cytotoxic SRIF analogue AN-238, consisting of 2-pyrrolinodoxorubicin (AN-201) linked to octapeptide SRIF carrier RC-12...
Article
We evaluated the effectiveness of targeted cytotoxic analog of somatostatin (SST) AN-238, consisting of 2-pyrrolinodoxorubicin (AN-201) linked covalently to SST octapeptide carrier RC-121 in DU-145 human androgen-independent prostate cancers xenografted into nude mice. We also investigated the expression of mRNAs for SST receptor subtypes 2A and 5...
Article
The efficacy of therapy with targeted cytotoxic luteinizing hormone-releasing hormone (LHRH) analog AN-207 consisting of superactive doxorubicin derivative AN-201 linked to carrier [D-Lys(6)]LH-RH was evaluated in vivo in nude mice bearing xenografts of MDA-PCa-2b prostate cancer line. AN-207 was administered intravenously (i.v.) at 200 nmol/kg on...
Article
The use of peptide analogs for the therapy of various cancers is reviewed. Inhibition of the pituitary–gonadal axis forms the basis for oncological applications of luteinizing hormone-releasing hormone (LH-RH) agonists and antagonists, but direct effects on tumors may also play a role. Analogs of somatostatin are likewise used for treatment of vari...
Article
BACKGROUND Cytotoxic analogs of somatostatin (SST), such as AN-238, which consists of 2-pyrrolinodoxorubicin (AN-201) linked to the SST carrier RC-121, can be targeted to tumors that express SST receptors. Because SST receptors are present in ovarian carcinoma cells, the authors evaluated the effect of AN-238 on the UCI-107 ovarian carcinoma cell l...
Article
Receptors for luteinizing hormone-releasing hormone (LHRH), expressed by ovarian cancers, can be used for targeting chemotherapeutic compounds more selectively to these tumors. We investigated the effects of cytotoxic LHRH analog AN-152, consisting of doxorubicin (DOX)-14-O-hemiglutarate linked to the epsilon-amino group of [D-Lys6]LHRH, on the gro...
Article
In this study, we present a spectroscopic study of the entry pattern of a chemotherapeutic drug (AN-152) and its carrier hormone ([D-Lys(6)]LH-RH) into living cancer cells, with the help of our two-photon probes and a home-built localized microspectrofluorometer coupled with two photon laser scanning microscope (TPLSM). Due to the inherent localiza...
Article
Targeting of cytotoxic agents represents a modern approach to the treatment of various cancers, that improves the efficacy and reduces peripheral toxicity. Recently we developed a powerful cytotoxic analog of luteinizing hormone-releasing hormone (LHRH), AN-207, designed to be targeted to tumors that express LHRH receptors. This analog consists of...
Article
The effectiveness of chemotherapy targeted to bombesin (BN) receptors was evaluated in nude mice bearing PC-3 human androgen-independent prostate cancers. Cytotoxic BN analogue AN-215, consisting of 2-pyrrolinodoxorubicin (AN-201) linked to BN-like carrier peptide RC-3094, was injected i.v. at 150 nmol/kg on days 1, 11 and 21. After treatment with...
Article
The effectiveness of chemotherapy targeted to bombesin (BN) receptors was evaluated in nude mice bearing PC-3 human androgen-independent prostate cancers. Cytotoxic BN analogue AN-215, consisting of 2-pyrrolinodoxorubicin (AN-201) linked to BN-like carrier peptide RC-3094, was injected i.v. at 150 nmol/kg on days 1, 11 and 21. After treatment with...
Article
The effectiveness of chemotherapy targeted to bombesin (BN) receptors was evaluated in nude mice bearing PC‐3 human androgen‐independent prostate cancers. Cytotoxic BN analogue AN‐215, consisting of 2‐pyrrolinodoxorubicin (AN‐201) linked to BN‐like carrier peptide RC‐3094, was injected i.v. at 150 nmol/kg on days 1, 11 and 21. After treatment with...
Article
The use of peptide analogs in the therapy of prostate cancer is reviewed. The preferred primary treatment of advanced androgen-dependent prostate cancer is presently based on the use of depot preparations of LH-RH agonists. This treatment is likewise recommended in patients with rising PSA levels after surgery or radiotherapy. LH-RH agonists with o...
Article
A highly potent derivative of doxorubicin, 2-pyrrolinodoxorubicin (AN-201), was linked to [D-Lys6]luteinizing hormone-releasing hormone (LH-RH) to form a cytotoxic analogue, AN-207, that can be targeted to LH-RH receptors. The effects of AN-207 were investigated in MDA-MB-435 human estrogen-independent breast carcinomas, which express LH-RH recepto...
Article
Characteristics of receptors for somatostatin (SST) analog RC-160 on 17 surgical specimens of human epithelial ovarian cancer and two human ovarian cancer lins were determined by ligand competition assays. The expression of mRNA for four SST receptor subrypes (sst1, sst3, sst2A, sst5) was investigated by RT-PCR. Thirteen of 17 specimens (76%) exhib...
Article
The use of peptide analogs in the therapy of prostate cancer is reviewed. The preferred primary treatment of advanced androgen‐dependent prostate cancer is presently based on the use of depot preparations of LH‐RH agonists. This treatment is likewise recommended in patients with rising PSA levels after surgery or radiotherapy. LH‐RH agonists with o...
Article
Full-text available
Targeting chemotherapy selectively to cancers can reduce the toxic side effects. AN-152, a conjugate of doxorubicin and [D-Lys6]-luteinizing hormone-releasing hormone (LH-RH), is more potent against LH-RH receptor-bearing cancers and produces less peripheral toxicity than doxorubicin. Many cancers, e.g., 50% of breast cancers, but few normal tissue...
Article
Full-text available
The sst2 somatostatin receptor mediates the antiproliferative effects of somatostatin analogs. The present study demonstrates that stable expression of sst2 in the hamster pancreatic cancer cells PC-1 and PC-1.0 activates an autocrine negative loop leading to an in vitro inhibition of cell proliferation. In vivo studies conducted in Syrian golden h...
Article
Receptor targeted chemotherapy is less toxic and more effective than conventional chemotherapy. Receptors for luteinizing hormone-releasing hormone (LH-RH) are found in about 50% of human breast cancers. Highly potent cytotoxic radical 2-pyrrolinodoxorubicin (AN-201) was linked to the agonistic analog [D-Lys6]LH-RH to form cytotoxic LH-RH analog AN...
Article
Recently, we developed a series of cytotoxic peptide conjugates containing 14-O-glutaryl esters of doxorubicin (DOX) or 2-pyrrolino-DOX (AN-201). Serum carboxylesterase enzymes (CE) can partially hydrolyze these conjugates in the circulation, releasing the cytotoxic radical, before the targeting is complete. CE activity in serum of nude mice is abo...
Article
Full-text available
Chemotherapy is commonly used in the treatment of cancers. However, the mechanism of action of many of these agents is not well understood. We present the synthesis of a two-photon fluorophore (C625) and its biological application when chemically linked to a chemotherapeutic agent (AN-152). By using two-photon laser-scanning microscopy, the drug:fl...
Article
Full-text available
Since somatostatin (sst) receptors are expressed in a high percentage of human breast cancers, we studied the effects of a targeted cytotoxic somatostatin analog (AN-238) formed by linking the highly active doxorubicin (DOX) derivative 2-pyrrolino-DOX (AN-201) to octapeptide RC-121 (D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH(2)) in 3 human breast cance...
Article
Cytotoxic agents linked to hormonal carriers provide new approaches to tumor therapy, and LH-RH receptors expressed by breast cancers can be used for targeting chemotherapeutic compounds. In the present study, large, advanced estrogen-independent MXT mouse mammary cancers were treated with cytotoxic LH-RH analog AN-152 containing doxorubicin (DOX)...
Article
Receptors for luteinizing hormone-releasing hormone (LH-RH) are found in about 50% of human breast carcinomas. A highly potent cytotoxic agent, 2-pyrrolinodoxorubicin (AN-201), was linked to the agonist [D-Lys6]LH-RH to form a cytotoxic LH-RH analog, AN-207, that can be targeted to LH-RH receptors on breast carcinomas. Nude mice bearing MX-1 hormon...
Article
The aim of the study was to investigate the effects of the cytotoxic analog of luteinizing hormone-releasing hormone AN-207 on the growth of the OV-1063 human epithelial ovarian cancers, which express luteinizing hormone-releasing hormone receptor. AN-207 consists of doxorubicin derivative 2-pyrrolinodoxorubicin (AN-201) linked with the carrier [D-...
Article
Recently, we developed two new cytotoxic analogs of luteinizing hormone-releasing hormone (LH-RH), AN-152 in which doxorubicin (DOX) is linked to [D-Lys6]LH-RH, and AN-207 which consists of 2-pyrrolino-DOX coupled to [D-Lys6]LH-RH. In this study, we examined binding of AN-152 and AN-207 to membranes of human breast cancer specimens and MCF-7 and MD...
Article
Receptors for luteinizing hormone-releasing hormone (LH-RH) found in prostate cancers might be used for targeting of chemotherapeutic agents. Doxorubicin derivative 2-pyrrolinodoxorubicin (AN-201) can be linked to carrier analog [D-Lys6]LH-RH to form the targeted cytotoxic analog of LH-RH, AN-207. We evaluated the effects of AN-207 and its componen...
Article
The selectivity of ligands specific for certain cells can be used to preferentially target chemotherapeutic compounds to neoplastic cells. Human breast, ovarian, endometrial, and prostatic cancers express receptors that can mediate the delivery of targeted cytotoxic compounds to neoplastic cells. Recently, a potent derivative of 2-pyrrolinodoxorubi...
Article
Full-text available
New approaches to target cytotoxic therapy specifically to metastatic prostate cancer sites are urgently needed. As such an approach, an inactive prodrug was synthesized by coupling the primary amine of doxorubicin to the COOH-terminal carboxyl of a seven-amino acid pep- tide carrier (i.e., Mu-His-Ser-Ser-Lys-Leu-Gln-Leu). The seven-amino acid pept...
Article
Full-text available
To create cytotoxic hybrid analogs of somatostatin (SST), octapeptides RC-160 (d-Phe-Cs-Trp-NH2) and RC-121 (d-Phe-Cs-Thr-NH2) were linked to doxorubicin (DOX) or its superactive derivative, 2-pyrrolino-DOX (AN-201). The conjugation was performed by coupling N-9-fluorenylmethoxycarbonyl (N-Fmoc)-DOX-14-O-hemiglutarate or 2-pyrrolino-DOX-14-O-hemigl...
Article
Receptors for luteinizing hormone-releasing hormone (LH-RH) are found in nearly 80% of human ovarian cancers. The chemotherapeutic agent doxorubicin can be linked to [D-lysine6]LH-RH to form a cytotoxic analogue (AN-152) that may have greater specificity for tumor cells. This study was conducted to investigate the effects of AN-152 on the growth of...
Article
Tumor inhibitory action and the optimal dosage regimens of highly potent targeted cytotoxic luteinizing hormone releasing hormone (LH-RH) analogs containing doxorubicin (DOX) or 2-pyrrolino-DOX (AN-201) were tested in female BDF mice bearing estrogen independent MXT mouse mammary cancers. The effects were compared to those obtained with the cytotox...
Article
Recently, we developed a targeted cytotoxic analog AN-207 of luteinizing hormone-releasing hormone (LH-RH), consisting of an intensely potent derivative of doxorubicin, 2-pyrrolinodoxorubicin (AN-201) conjugated to carrier agonist [D-Lys6]LH-RH. In this study, we investigated the effects of cytotoxic analog AN-207, designed for targeted chemotherap...
Article
Zarandi, M., M. Kovacs, J. E. Horvath, K. Toth, G. Halmos, K. Groot, A. Nagy, Z. Kele, and A. V. Schally, Synthesis and in vitro evaluation of new potent antagonists of growth hormone-releasing hormone (GH-RH). Peptides 18(3) 423–430, 1997.—In the search for more potent antagonists of hGH-RH, 20 new analogs were synthesized, purified and tested in...
Article
Female BDF mice bearing estrogen-dependent MXT mouse mammary cancers were treated for 4 weeks with a cytotoxic analog of luteinizing hormone-releasing hormone (LH-RH), T-98 (agonist [D-Lys6]LH-RH linked to glutaryl-2(hydroxymethyl)anthraquinone). The effects of T-98 were compared to those of equimolar amounts of the cytotoxic moiety 2-(hydroxymethy...
Article
The binding and internalization of a cytotoxic analogue of luteinizing hormone-releasing hormone (LH-RH), T-98 (agonist [d-Lys6]LH-RH linked to glutaryl-2-(hydroxymethyl)anthraquinone), by rat anterior pituitary cells was investigated. Analogue T-98 was bound to pituitary membrane binding sites for LH-RH with a high affinity () and was 17 times mor...
Article
A series of new highly potent LH-RH antagonists (T-series) has been synthesized in our laboratory. Among these analogs, antagonists [Ac-d-Nal(2), d-Phe(4Cl)2. d-Pal(3)3, d-Lys(A2pr(Car)2)6, d-Ala10LH-RH (T-140); [Ac-d-Nal(2)1, d-Phe(4Cl)2, d-Pal(3)3, d-Lys(A2pr(Ac)2)6, d-Ala10]LH-RH (T-148); [Ac-d-Nal(2)1, d-Phe(4Cl)2, d-Pal(3)3, d-Lys(A2pr(For)2)6...
Article
The effects of hybrid cytotoxic LH-RH analogs, produced by linking anthraquinone or methotrexate to carrier LH-RH agonist [D-Lys6]LH-RH, were evaluated in Copenhagen-Fisher F1 rats bearing Dunning R-3327H prostate adenocarcinoma. The two cytotoxic LH-RH analogs T-98 [(D-Lys6)LH-RH coupled to glutaryl-2-(hydroxymethyl)anthraquinone (G-HMAQ)], and AJ...
Article
Cytotoxic luteinizing hormone-releasing hormone (LH-RH) analogs, AJ-004 (agonist [D-Lys6]LH-RH linked to methotrexate (MTX)), T-98 ([D-Lys6]LH-RH coupled to glutaryl-2-(hydroxymethyl)anthraquinone) (G-HMAQ) and T-121/B (antagonist containing two residues of G-HMAQ) were tested in female BDF1 mice bearing MXT ((3.2)/Ovex) estrogen-independent mammar...
Article
Seven new antagonists of bombesin (Bn)/gastrin-releasing peptide (GRP) containing C-terminal Trp or Tpi (2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-3-carboxylic acid) in a reduced peptide bond were synthesized by solid phase methods and evaluated biologically. The reduced bond in four [Leu13 psi(CH2NH)Trp14]Bn(6-14) analogs was formed by reductive al...

Citations

... Sun et al. reported that approximately 60% of primary prostate cancer cells express GRPR (Sun et al., 2000a). In vitro and in vivo ablation of the GRP/GRPR autocrine pathway using a GRP neutralizing antibody or bombesin analogs resulted in the inhibition of tumor growth in preclinical models of SCLC, NSCLC and prostate cancer in addition to HNSCC (Kelley et al., 1997; Siegfried et al., 1999; Plonowski et al., 2000). The therapeutic efficacy of the GRP neutralizing antibody (2A11) in SCLC is under clinical investigation (Kelley et al., 1997; Chaudhry et al., 1999). ...
... Over expression of luteinizing hormone releasing hormone (LHRH) receptors in hormone-associated cancers makes it another attractive target for a selective delivery of chemotherapeutics. In the mid-1980s, analogs of LHRH peptide were introduced to target LHRH receptor in prostate [114] and breast [115] cancers. Since then this class of peptides has been extensively tested as carriers of chemotherapeutic agents to cancer cells. ...
... RT-PCR reaction was performed in 25 µL reaction volume with gene-specific primers. The primers for PCR amplification were designed using the published sequences for the respective genes as shown in Table 4. Primer sequences with as small as possible homology among SST receptor subtypes were selected as described before [6,8]. PCR reaction was performed in a C1000 TM Thermal Cycler RT-PCR system (Bio-Rad Laboratories, Inc.). ...
... For example, prostate cancer imaging probes are able to target receptors such as the gastrin-releasing peptide receptor (GRP-R), a G protein-coupled receptor, as well as prostate-specific membrane antigen, a transmembrane protein, which are overexpressed on prostate cancer cells Patel et al., 2006;Maurer et al., 2016;Rauscher et al., 2016). Targeting overexpressed receptors can also be used for therapeutic purposes, as was shown by Plonowski et al., where a cytotoxic bombesin analog was developed that targeted GRP-R and inhibited the growth of prostate cancer (Plonowski et al., 2000). ...
... As an in vitro proof of principle for such a PSA-activated prodrug approach, we collaborated with Andrew V. Schally, Department of Medicine, Tulane University School of Medicine and Veterans Affairs Medical Center, New Orleans, Louisiana to couple the primary amine of doxorubicin via a peptide bond to the carboxylic acid group of the 7AA lead peptide [51]. These studies documented that such a doxorubicin-peptide prodrug selectively kills cells that express enzymatically active PSA [52]. ...
... Among all SST receptors, SSTR2 is the most abundant (19). Additionally, SSTR2 is expressed in human pancreatic tissue, but could be loss in pancreatic cancers and derived cell lines (37)(38)(39). Previous studies have demonstrated that the combination of SST and SSTR2 could inhibit cytokine release from immune cells (26). ...
... During the past years, multiple antagonists of human growth hormone-releasing hormone (hGHRH) have been synthesized and tested by other investigators [11,63,[65][66][67], as well as by us [38][39][40][81][82][83][88][89][90]. Studies performed in our laboratory showed, that GHRH antagonists inhibit the growth of human osteosarcomas (SK-ES-1 and MNNG/HOS) [52] and small cell-and non-small cell lung carcinomas [53] xenografted into nude mice. ...
... In addition, the concentration needed to kill tumour cells is close to drug levels which produce severe toxicity to normal cells in the body. To circumvent some of these problems anthracycline antibiotics have been conjugated to carriers such as peptide or steroidal hormones, which are recognized by homologous either membranal or nuclear associated steroid receptors present in tumour cells123456 . Although some of the receptor mediated cytotoxic drug conjugates appeared promising in vitro, their use in vivo was generally ineffective. ...
... BBN (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) and its derivatives have been extensively used for the development of molecular probes for imaging of GRPR on tumors (42,43). However, natural BBN (1-14), a receptor agonist, binds to GRPR to promote the proliferation of tumor cells and causes side effects such as gastrointestinal discomfort (44,45). In recent years, receptor antagonists have been developed and studied by modifications on the C terminal amino acids of BBN for the diagnosis and treatment of tumors (46,47). ...