scholarly journals High expression of gastrin-releasing peptide receptors in the vascular bed of urinary tract cancers: promising candidates for vascular targeting applications

2009 ◽  
Vol 16 (2) ◽  
pp. 623-633 ◽  
Author(s):  
Achim Fleischmann ◽  
Beatrice Waser ◽  
Jean Claude Reubi

Tumoral gastrin-releasing peptide (GRP) receptors are potential targets for diagnosis and therapy using radiolabeled or cytotoxic GRP analogs. GRP-receptor overexpression has been detected in endocrine-related cancer cells and, more recently, also in the vascular bed of selected tumors. More information on vascular GRP-receptors in cancer is required to asses their potential for vascular targeting applications. Therefore, frequent human cancers (n=368) were analyzed using in vitro GRP-receptor autoradiography on tissue sections with the 125I-[Tyr4]-bombesin radioligand and/or the universal radioligand 125I-[d-Tyr6, β-Ala11, Phe13, Nle14]-bombesin(6–14). GRP-receptor expressing vessels were evaluated in each tumor group for prevalence, quantity (vascular score), and GRP-receptor density. Prevalence of vascular GRP-receptors was variable, ranging from 12% (prostate cancer) to 92% (urinary tract cancer). Different tumor types within a given site had divergent prevalence of vascular GRP-receptors (e.g. lung: small cell cancer: 0%; adenocarcinoma: 59%; squamous carcinoma: 83%). Also the vascular score varied widely, with the highest score in urinary tract cancer (1.69), moderate scores in lung (0.91), colon (0.88), kidney (0.84), and biliary tract (0.69) cancers and low scores in breast (0.39) and prostate (0.14) cancers. Vascular GRP-receptors were expressed in the muscular vessel wall in moderate to high densities. Normal non-neoplastic control tissues from these organs lacked vascular GRP-receptors. In conclusion, tumoral vessels in all evaluated sites express GRP-receptors, suggesting a major biological function of GRP-receptors in neovasculature. Vascular GRP-receptor expression varies between the tumor types indicating tumor-specific mechanisms in their regulation. Urinary tract cancers express vascular GRP-receptors so abundantly, that they are promising candidates for vascular targeting applications.

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e14575-e14575
Author(s):  
A. M. Fleischmann ◽  
B. Waser ◽  
J. C. Reubi

e14575 Background: Tumoral Gastrin-releasing peptide (GRP) receptors are potential targets for diagnosis and therapy using radiolabeled or cytotoxic GRP analogs. GRP-receptor overexpression has been detected in cancer cells and, more recently, also in the vascular bed of selected tumors. More information on vascular GRP-receptors in cancer is required to asses their potential for vascular targeting applications. Methods: Frequent human cancers from the breast (n=134), lung (n=57), prostate (n=50), kidney (n=32), colon (n=46), urinary tract (n=26) and biliary tract (n=23) were analyzed using in vitro GRP-receptor autoradiography on tissue sections with the 125I-[Tyr4]-bombesin radioligand and/or the universal radioligand 125I-[D-Tyr6, ß-Ala11, Phe13, Nle14]-bombesin(6–14). GRP-receptor expressing tumoral vessels were evaluated in each tumor group for prevalence, quantity (vascular score) and GRP-receptor density. Results: Prevalence of vascular GRP-receptors is variable, ranging from 13% (prostate cancer) to 92% (urinary tract cancer). Different tumor-types within a given site may have divergent prevalence of vascular GRP-receptors (e.g. lung: small cell cancer: 0%; adenocarcinoma: 59%; squamous carcinoma: 83%). Also the vascular score varies widely, with highest score in urinary tract cancer (1.69), moderate scores in lung (0.91), colon (0.88), kidney (0.84) and biliary tract (0.69) cancers and low scores in breast (0.39) and prostate (0.14) cancers. Vascular GRP-receptors are expressed in the muscular vessel wall in moderate to high densities. Normal non- neoplastic control tissues from these organs lack vascular GRP-receptors. Conclusions: Tumoral vessels in all evaluated sites overexpress GRP-receptors, suggesting a major biological function of GRP-receptors in the tumor vascular bed. Vascular GRP-receptor expression varies between the tumor-types indicating tumor-specific mechanisms in their regulation. Urinary tract cancers express vascular GRP-receptors so abundantly, that they are promising candidates for vascular targeting applications. No significant financial relationships to disclose.


2007 ◽  
Vol 29 (5) ◽  
pp. 421-433 ◽  
Author(s):  
Achim Fleischmann ◽  
Beatrice Waser ◽  
Jean Claude Reubi

Background: Peptide receptors, overexpressed in specific cancers, represent new diagnostic and therapeutic targets. In this study, receptors for the gastrin-releasing peptide (GRP), and other members of the bombesin-family of peptides, were evaluated in ovarian neoplasms. Methods: 75 primary, secondary and metastatic ovarian tumors were investigated for their bombesin-receptor subtype expression, incidence, localization and density using in vitro autoradiography on tissue sections with the universal radioligand 125I-[D-Tyr6, ß-Ala11, Phe13, Nle14]-bombesin(6-14) and the GRP-receptor subtype-preferring 125I-[Tyr4]-bombesin. Results: GRP-receptors were detected in 42/61 primary ovarian tumors; other bombesin-receptor subtypes (BB1, bb3) were rarely present (3/61). Two different tissue compartments expressed GRP-receptors: the tumoral vasculature was the predominant site of GRP-receptor expression (38/61), whereas neoplastic cells more rarely expressed GRP-receptors (14/61). GRP-receptor positive vessels were present in the various classes of ovarian tumors; generally, malignant tumors had a higher incidence of GRP-receptor positive vessels compared to their benign counterparts. The prevalence of such vessels was particularly high in ovarian carcinomas (16/19) and their metastases (5/5). The GRP-receptors were expressed in high density in the muscular vessel wall. Normal ovary (n=10) lacked GRP-receptors. Conclusions: The large amounts of GRP-receptors in ovarian tumor vessels suggest a role in tumoral vasculature and possibly angiogenesis. Further, these vessels might be targeted in vivo with bombesin analogs for diagnosis or for therapy.


Choonpa Igaku ◽  
2010 ◽  
Vol 37 (2) ◽  
pp. 107-114
Author(s):  
Shuichi MIHARA ◽  
Kouji OTAKE ◽  
Hiroyuki KOBA ◽  
Shinji TANAKA ◽  
Shinichi HIRAO

Medicine ◽  
2016 ◽  
Vol 95 (49) ◽  
pp. e5594 ◽  
Author(s):  
Chien-Liang Lin ◽  
Wen-Tsung Huang ◽  
Wen-Chou Fan ◽  
Yin-Hsun Feng ◽  
Chia-Ho Lin ◽  
...  

2010 ◽  
Vol 183 (1) ◽  
pp. 56-61 ◽  
Author(s):  
Wen-Jeng Wu ◽  
Hung-Lung Ke ◽  
Yi-Hsin Yang ◽  
Ching-Chia Li ◽  
Yii-Her Chou ◽  
...  

2013 ◽  
Vol 12 (2) ◽  
pp. 279-284 ◽  
Author(s):  
Inge Thomsen Bernstein ◽  
Torben Myrhøj

1983 ◽  
Vol 69 (3) ◽  
pp. 221-222 ◽  
Author(s):  
Maura Ludovici ◽  
Piero Dolara ◽  
Alfiero Costantini ◽  
Guido Barbagli ◽  
Anna Calzolai ◽  
...  

The metabolism of antipyrine was studied in 13 patients with cancer and bladder papillomas and in 11 control subjects, matched for interfering factors like smoking, diet, age and sex. The mean antipyrine half-life was significantly longer in patients with urinary tract cancer (14.7 ± 1.32 h SE) than in control subjects (11 ± 0.55 h SE) (P < 0.025); other clinical parameters did not vary.


2014 ◽  
Vol 11 (1) ◽  
pp. 70-80
Author(s):  
Baghdad Science Journal

The activity of Alanine aminopeptidase( AAP ) was measured in the urine of healthy and urinary tract cancer patients , the results showed higher activity of (AAP) in patients compared to healthy . AAP was Purified from the urine of healthy and patients with urinary tract cancer by dialysis and gel filtration (Sephadex G – 50) and two isoenzymes of (AAP) were separated from urine by using ion-exchang resin (DEAE – Sephadex A – 50 ) in previous study. The kinetics studies showed that both isoenzymes I and II obeyed Michaelis – Menton equation . with optimal concentration of alanine-4-nitroanilide as substrate for isoenzymes I and II which was (2 x 10-3 mol/L ). The two isoenzymes obeyed Arrhenius equation up two 37° C and their Ea and Q10 constants were determined . The binding of alanine-4-nitroanilide by two isoenzymes I , II were studied and the kinetic constant ( k+1 , k-1 , Ka , Ks ) were indicated that the reaction was first order at 37° C .Thermodynamic parameters of the standard state ( ?G°, ?H° , ?S° ) and the transition state ( ?G*, ?H* , ?S* ) were determined by using Vant Hoff and Arrhenius equations.


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