Clinical correlates of bombesin-like peptide receptor subtype expression in human lung cancer cells

Toi-Scott, Miho; Jones, Calvin E.; Kane, Madeleine A.

doi:10.1016/0169-5002(95)00597-8

Cited by 60 publications

(22 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…And in the only clinical study performed to date, provision of a GRP monoclonal antibody to 13 patients with small cell lung cancer did not significantly alter tumor cell growth or patient outcome; indeed, the best effect was noted in a patient whose tumor showed no evidence of secreting bioactive GRP [25]. In contrast, a small study found that patients whose lung cancer expressed GRPR had a mean survival of 367 ± 274 days while patients whose tumors did not survived 211 ± 114 days [26]. While this difference in survival was not statistically significant, it nonetheless remains important because it failed to demonstrate that aberrant expression of this peptide hormone receptor worsened patient outcome.…”

Section: Introductionmentioning

confidence: 79%

“…This difference was not statistically significant; a finding similar to what has been observed for patients with GRPR-positive and GRPR-negative cancers arising from the lung and stomach. For instance, patients whose small cell lung cancer expressed GRPR had a mean survival of 367 ± 274 days while patients whose tumors did not survived 211 ± 114 days [26]. Likewise, patients whose gastric cancer expressed functional GRPR survived 556 ± 294 days whereas patients whose tumors did not express this receptor survived 249 ± 54 days [39].…”

Section: Discussionmentioning

confidence: 97%

See 1 more Smart Citation

Expression of GRP and its receptor is associated with improved survival in patients with colon cancer

Rivera

Ahlberg

Taglia

et al. 2009

Clin Exp Metastasis

View full text Add to dashboard Cite

Epithelial cells lining the adult human colon do not normally express gastrin releasing peptide (GRP) or its receptor (GRPR), but both can be up regulated post malignant transformation. However, controversy exists as to the contribution these proteins make to tumor cell behavior once present. Since GRPR activation promotes proliferation, it has been assumed that their aberrant expression promotes colon cancer (CC) growth and progression. Yet we have contended that when expressed, GRP/GRPR benefits the host since in vitro studies demonstrate they enhance tumor cell attachment to the extracellular matrix and promote CC cytolysis by natural killer lymphocytes. Thus the aim of this study was to ascertain the effect of aberrant GRP/GRPR expression on patient survival. To do this we identified all CC diagnosed at a single institution from 1998 to 2002 that were classified as AJCC stage II or III (n = 88); of these 50 (57%) had sufficient tissues remaining for study. GRP/GRPR expression and natural killer cell density were determined immunohistochemically at the leading edge of each CC, and survival assessed by Kaplan Meier analysis. Expression of high levels of GRPR alone, or both GRP and GRPR, was associated with delayed CC recurrence (14.1-17.0 months, respectfully; P = 0.005) and increased survival (10.1-13.1 months, respectfully; P = 0.0124). CC expressing GRP/GRPR were associated with significantly fewer lymph node metastases than tumors not expressing these proteins, and contained significantly more CD16 + natural killer cells, than tumors not expressing these proteins. These findings demonstrate that patients whose CC express GRPR are associated with a survival advantage as compared to those whose CC do not express these proteins.

show abstract

Section: Introductionmentioning

confidence: 79%

Section: Discussionmentioning

confidence: 97%

Expression of GRP and its receptor is associated with improved survival in patients with colon cancer

Rivera

Ahlberg

Taglia

et al. 2009

Clin Exp Metastasis

View full text Add to dashboard Cite

show abstract

“…Only small amounts of activity remained in the kidneys, stomach and liver at 4 h postinjection (2.66 ( 0.70, 1.16 ( 0.05 and 0.83 ( 0.23% ID/g, respectively). The pancreas, which expresses BN receptors (39), has been used as a target by other investigators (25,45) for the biological evaluation of newly developed radiolabeled BN analogues. In this study, a significant uptake (21.83 ( 2.88% ID/g, 15 min postinjection) of the radioactivity was found in the pancreas.…”

Section: Resultsmentioning

confidence: 99%

A New High Affinity Technetium Analogue of Bombesin Containing DTPA as a Pharmacokinetic Modifier

et al. 2004

View full text Add to dashboard Cite

The bombesin (BN)/gastrin-releasing peptide (GRP) receptor is expressed in high density on the cell surface of a variety of tumors. This makes the receptors accessible as a molecular target for the detection of lesions in which they are expressed. In this study, we describe a high affinity hydrophilic (99m)Tc-labeled BN analogue, [DTPA(1), Lys(3)((99m)Tc-Hx-DADT), Tyr(4)]BN, having diethylenetriaminepentaacetic acid (DTPA), as a build-in pharmacokinetic modifier, to direct its excretion through the urinary system in order to lower abdominal background activity. In vitro binding studies using [(125)I-Tyr(4)]BN (K(d), 0.1 nM) and human prostate cancer PC-3 cell membranes showed that the inhibition constant (K(i)) of [DTPA(1), Lys(3)((99)Tc-Hx-DADT), Tyr(4)]BN was 19.9 +/- 8.0 nM. Biodistribution studies in normal mice showed fast blood clearance (0.15 +/- 0.01% ID/g, 4 h postinjection), low intestinal accumulation (9.16 +/- 2.35% ID/g, 4 h postinjection), and significant uptake in BN/GRP receptor rich tissues such as the pancreas (21.83 +/- 2.88% ID/g, 15 min postinjection). The pancreas/blood, pancreas/muscle, and pancreas/liver ratios were highest at 2 h postinjection at 23, 74, and 8.4, respectively. The uptake in the pancreas could be blocked by BN (11.96 +/- 1.17 vs 0.65 +/- 0.16% ID/g), partially blocked by neuromedin B (11.96 +/- 1.17 vs 6.66 +/- 0.51% ID/g), but not affected by somatostatin (11.96 +/- 1.17 vs 12.91 +/- 2.53% ID/g), indicating that the binding of [DTPA(1), Lys(3)((99m)Tc-Hx-DADT), Tyr(4)]BN to the receptors was specific. Scintigraphic imaging of human PC-3 prostate cancer xenografts in SCID mice gave a high target to nontarget ratio on the image. Thus, [DTPA(1), Lys(3)((99m)Tc-Hx-DADT), Tyr(4)]BN has the potential for imaging BN/GRP receptor-positive lesions.

show abstract

“…Bombesin receptors, a subtype of the regulatory gastrin-releasing peptide (GRP), 98 are expressed in tumors such as breast, 99 prostate, 100 and lung, 101 and have been speculated to function with mitogenic activity. 102 In an effort to target GRPr-positive tumors in mouse models of prostate cancer, Mansi et al 103 compared a bombesin PET tracer antagonist ( 68 Ga-RM2) with the analogous SPECT tracer ( 111 In-RM2).…”

Section: Radiogallium Labeled Compoundsmentioning

confidence: 99%

The Next Generation of Positron Emission Tomography Radiopharmaceuticals in Oncology

Rice

Roney

Daumar

et al. 2011

Seminars in Nuclear Medicine

View full text Add to dashboard Cite

Although 18F-fluorodeoxyglucose (18F-FDG) is still the most widely used positron emission tomography (PET) radiotracer, there are a few well-known limitations to its use. The last decade has seen the development of new PET probes for in vivo visualization of specific molecular targets, along with important technical advances in the production of positron-emitting radionuclides and their related labeling methods. As such, a broad range of new PET tracers are in preclinical development or have recently entered clinical trials. The topics covered in this review include labeling methods, biological targets, and the most recent preclinical or clinical data of some of the next generation of PET radiopharmaceuticals. This review, which is by no means exhaustive, has been separated into sections related to the PET radionuclide used for radiolabeling: fluorine-18, for the labeling of agents such as FACBC, FDHT, choline, and Galacto-RGD; carbon-11, for the labeling of choline; gallium-68, for the labeling of peptides such as DOTATOC and bombesin analogs; and the long-lived radionuclides iodine-124 and zirconium-89 for the labeling of monoclonal antibodies cG250, and J591 and trastuzumab, respectively.

show abstract

Clinical correlates of bombesin-like peptide receptor subtype expression in human lung cancer cells

Cited by 60 publications

References 29 publications

Expression of GRP and its receptor is associated with improved survival in patients with colon cancer

Expression of GRP and its receptor is associated with improved survival in patients with colon cancer

A New High Affinity Technetium Analogue of Bombesin Containing DTPA as a Pharmacokinetic Modifier

The Next Generation of Positron Emission Tomography Radiopharmaceuticals in Oncology

Contact Info

Product

Resources

About