Differing effects of microtubule depolymerizing and stabilizing chemotherapeutic agents on t-SNARE–mediated apical targeting of prostate-specific membrane antigen

Christiansen, Jason; Weimbs, Thomas; Bander, Neil H.; Rajasekaran, Ayyappan K.

doi:10.1158/1535-7163.mct-06-0253

Cited by 3 publications

(2 citation statements)

References 32 publications

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“…with conjugation of membrane-destabilizing synthetic polymers such as poly(propylacrylic acid [32]) or antigen accessibility (e.g. with microtubule depolymerizing drugs in the case of PSMA-targeting [33]) can potentially be evaluated.…”

Section: Discussionmentioning

confidence: 99%

Pairwise comparison of 89Zr- and 124I-labeled cG250 based on positron emission tomography imaging and nonlinear immunokinetic modeling: in vivo carbonic anhydrase IX receptor binding and internalization in mouse xenografts of clear-cell renal cell carcinoma

Cheal

Punzalan

Doran

et al. 2014

Eur J Nucl Med Mol Imaging

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Purpose The positron-emitting tomography (PET) tracer, 124I-cG250, directed against carbonic anhydrase IX (CAIX) shows promise for pre-surgical diagnosis of clear renal cell carcinoma (cRCC) [1, 2]. The radiometal zirconium-89 (89Zr), however, may offer advantages as a surrogate PET nuclide over 124I in terms of greater tumor uptake and retention [3]. In the current report, we have developed a non-linear immunokinetic model to facilitate a quantitative comparison of absolute uptake and antibody turnover between 124I-cG250 and 89Zr- cG250 using a human cRCC xenograft tumor model in mice. We believe that his unique model better relates quantitative imaging data to the salient biologic features of tumor antibody-antigen binding and turnover. Methods We conducted experiments with 89Zr-cG250 and 124I-cG250 using a human ccRCC cell line (SK-RC-38) to characterize the binding affinity and internalization kinetics of the two tracers in vitro. Serial-PET imaging was performed in mice bearing sub-cutaneous cRCC tumors to simultaneously detect and quantify time-dependent tumor uptake in vivo. Using the known specific activities of the two tracers, the equilibrium rates of antibody internalization and turnover in the tumor were derived from the PET images using non-linear compartmental modeling. Results The two tracers demonstrate virtually identical tumor-cell binding and internalization but with markedly different retentions in vitro. Superior PET images were obtained using 89Zr-cG250, owing to the more prolonged trapping of the radiolabel in the tumor and simultaneous wash-out from normal tissues. Estimates of cG250-CAIX complex turnover were 1.35–5.51 × 1012 molecules per hour per gram of tumor (20% of receptors internalized per hour), and the ratio of 124I/89Zr atoms released per unit time by tumor was 17.5. Conclusions Pairwise evaluation of 89Zr-cG250 and 124I-cG250 provided the basis for a non-linear immunokinetic model which yielded quantitative information about the binding and internalization of radioantibody bound to CAIX on tumor cells in vivo. 89Zr-cG250 is likely to provide high-quality PET images and may be a useful tool to quantify CAIX/cG250 receptor turnover and cG250-accessible antigen density non-invasively in man.

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Section: Discussionmentioning

confidence: 99%

Pairwise comparison of 89Zr- and 124I-labeled cG250 based on positron emission tomography imaging and nonlinear immunokinetic modeling: in vivo carbonic anhydrase IX receptor binding and internalization in mouse xenografts of clear-cell renal cell carcinoma

Cheal

Punzalan

Doran

et al. 2014

Eur J Nucl Med Mol Imaging

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“… 35 – 37 These favorable outcomes which were achieved using microtubule targeted agents have rekindled interest in such therapies for the clinical management of prostate cancer. 38 Li et al 39 found 2,3′,4,4′,5′-pentamethoxy-trans-stilbene, which targeted microtules, to be a potent inducer of apoptosis in colon cancer cells. Chopra et al 40 reported that novel piperazine-based compounds inhibited microtubule dynamics and sensitized colon cancer cells to tumor necrosis factor-induced apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Colchicine Significantly Reduces Incident Cancer in Gout Male Patients

2015

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Patients with gout are more likely to develop most cancers than subjects without gout. Colchicine has been used for the treatment and prevention of gouty arthritis and has been reported to have an anticancer effect in vitro. However, to date no study has evaluated the relationship between colchicine use and incident cancers in patients with gout. This study enrolled male patients with gout identified in Taiwan's National Health Insurance Database for the years 1998 to 2011. Each gout patient was matched with 4 male controls by age and by month and year of first diagnosis, and was followed up until 2011. The study excluded those who were diagnosed with diabetes or any type of cancer within the year following enrollment. We calculated hazard ratio (HR), aged-adjusted standardized incidence ratio, and incidence of 1000 person-years analyses to evaluate cancer risk. A total of 24,050 male patients with gout and 76,129 male nongout controls were included. Patients with gout had a higher rate of incident all-cause cancers than controls (6.68% vs 6.43%, P = 0.006). A total of 13,679 patients with gout were defined as having been ever-users of colchicine and 10,371 patients with gout were defined as being never-users of colchicine. Ever-users of colchicine had a significantly lower HR of incident all-cause cancers than never-users of colchicine after adjustment for age (HR = 0.85, 95% CI = 0.77–0.94; P = 0.001). In conclusion, colchicine use was associated with a decreased risk of incident all-cause cancers in male Taiwanese patients with gout.

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Docetaxel down‐regulates the expression of androgen receptor and prostate‐specific antigen but not prostate‐specific membrane antigen in prostate cancer cell lines: Implications for PSA surrogacy

Kuroda¹,

Liu²,

Kim³

et al. 2009

The Prostate

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While DOC did not affect PSMA expression, it was unexpectedly found to down-regulate AR and PSA. DOC-induced down-regulation of AR might be one of the anti-tumor mechanisms active in PC. Down-regulation of PSA may account for the significantly higher PSA response rates (45-50%) relative to measurable response rates (8-17%) reported in DOC PC trials and have implications for PSA surrogacy observations derived from DOC trials.

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Differing effects of microtubule depolymerizing and stabilizing chemotherapeutic agents on t-SNARE–mediated apical targeting of prostate-specific membrane antigen

Cited by 3 publications

References 32 publications

Pairwise comparison of 89Zr- and 124I-labeled cG250 based on positron emission tomography imaging and nonlinear immunokinetic modeling: in vivo carbonic anhydrase IX receptor binding and internalization in mouse xenografts of clear-cell renal cell carcinoma

Pairwise comparison of 89Zr- and 124I-labeled cG250 based on positron emission tomography imaging and nonlinear immunokinetic modeling: in vivo carbonic anhydrase IX receptor binding and internalization in mouse xenografts of clear-cell renal cell carcinoma

Colchicine Significantly Reduces Incident Cancer in Gout Male Patients

Docetaxel down‐regulates the expression of androgen receptor and prostate‐specific antigen but not prostate‐specific membrane antigen in prostate cancer cell lines: Implications for PSA surrogacy

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