Serial Biopsies/Fine-Needle Aspirates and Their Assessment

Boeddinghaus, Irene; Johnson, Stephen R. D.

doi:10.1385/1-59259-969-9:29

Cited by 6 publications

(8 citation statements)

References 17 publications

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“…5 Serial biopsy of lesions has been introduced as a means to overcome the problems associated with simple biopsy assessment, particularly for monitoring treatment response. 6 However, serial biopsy sampling may still suffer from the drawback that the results can be confounded by tumor heterogeneity.…”

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confidence: 99%

PET Imaging of Steroid Hormone Receptor Expression

et al. 2015

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Steroid hormone receptor (SHR) expression and changes in SHR expression compared to basal levels, whether upregulated, downregulated, or mutated, form a distinguishing feature of some breast, ovarian, and prostate cancers. These receptors act to induce tumor proliferation. In the imaging context, total expression together with modulation of expression can yield predictive and prognostic information. Currently, biopsy for histologic assessment of SHR expression is routine for breast and prostate cancer; however, the technique is not well suited to the heterogeneous tumor environment and can lead to incorrect receptor expression assignment, which precludes effective treatment. The development of positron emission tomography (PET) radioligands to image receptor expression may overcome the difficulties associated with tumor heterogeneity and facilitate the assessment of metastatic disease.

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confidence: 99%

PET Imaging of Steroid Hormone Receptor Expression

et al. 2015

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“…Fine needle aspiration (FNA) is an inexpensive biopsy technique that is established as a reliable method for diagnosis based on isolated or grouped cells (21, 22). Early studies demonstrated that FNA samples are representative of the overall tumor phenotype (23, 24).…”

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confidence: 99%

Measurement of conatumumab‐induced apoptotic activity in tumors by fine needle aspirate sampling

et al. 2010

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Conatumumab is a monoclonal antibody specific for death receptor 5 (DR5) that activates caspases leading to DNA fragmentation and tumor-cell death. Like other Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) receptor therapies, conatumumab is currently being evaluated in clinical trials across a variety of tumor types. However, molecular evidence of on-target drug activity in tumors is often an elusive goal for clinical investigation. Here we evaluated a translational approach using a relevant biopsy method, fine needle aspirates (FNAs), to study the on-target pharmacodynamics of conatumumab pre-clinically. As detected by laser scanning cytometry, druginduced caspase-3 activation in FNA biopsies of Colo205 xenografts correlated well with activated caspase-3 in conventional section-based samples. Furthermore, in tumor-bearing mice, surrogate assays of serum caspase-3/7 activity and serum drug exposure correlated with in situ caspase-3 activation. We found that one advantage of FNA sampling over other sampling techniques was the ability to measure caspase activity on a per cell basis using DNA content information. To adapt the utility of FNAs for measuring pharmacodynamic markers in humans, detection of activated caspase-3 was multiplexed with EpCAM to characterize mock and clinical FNAs from colorectal and nonsmall cell lung cancer patients. These data suggest that FNA sampling is a practical method to cytometrically evaluate tumors for pharmacological impact in a clinical setting. '

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“…Fine-needle aspiration is an inexpensive biopsy technique used routinely for diagnosis [20,21] and has recently been adapted for immunocytochemical analysis of signal transduction pathways [12,13]. The LSC cytometric platform is well-suited for FNA sample analysis: 1) it is capable of assessing small numbers of cells from complex tissues such as tumor; 2) it retains the overall tumor phenotype [12-14,22-25] Additional file 3: Figure S3A.…”

Section: Resultsmentioning

confidence: 99%

AMG 900, a potent inhibitor of aurora kinases causes pharmacodynamic changes in p-Histone H3 immunoreactivity in human tumor xenografts and proliferating mouse tissues

Juan¹,

Bush

Ma³

et al. 2014

J Transl Med

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BackgroundThe Aurora family of serine-threonine kinases are essential regulators of cell division in mammalian cells. Aurora-A and –B expression and kinase activity is elevated in a variety of human cancers and is associated with high proliferation rates and poor prognosis. AMG 900 is a highly potent and selective pan-aurora kinase inhibitor that has entered clinical evaluation in adult patients with advanced cancers. In mice, oral administration of AMG 900 blocks the phosphorylation of histone H3 on serine-10 (p-Histone H3), a proximal substrate of aurora-B and inhibits the growth of multiple human tumor xenografts, including multidrug-resistant models.MethodsIn order to establish a preclinical pharmacokinetic-pharmacodynamic (PK-PD) relationship for AMG 900 that could be translated to the clinic, we used flow cytometry and laser scanning cytometry detection platforms to assess the effects on p-Histone H3 inhibition in terms of sensitivity, precision, and specificity, in human tumor xenografts in conjunction with mouse skin and bone marrow tissues. Mice with established COLO 205 tumors were administered AMG 900 at 3.75, 7.5, and 15 mg/kg and assessed after 3 hours.ResultsSignificant suppression of p-Histone H3 in mouse skin was only observed at 15 mg/kg (p <0.0001), whereas in mouse bone marrow and in tumor a dose-dependent inhibition was achieved at all three doses (p ≤0.00015). These studies demonstrate that AMG 900 inhibits p-Histone H3 in tumors and surrogate tissues (although tissues such as skin may be less sensitive for assessing PD effects). To further extend our work, we evaluated the feasibility of measuring p-Histone H3 using fine-needle aspirate (FNA) tumor xenograft biopsies. Treatment with AMG 900 significantly inhibited p-Histone H3 (>99% inhibition, p <0.0001) in COLO 205 tumors. Lastly, we illustrate this LSC-based approach can detect p-Histone H3 positive cells using mock FNAs from primary human breast tumor tissues.ConclusionPhosphorylation of histone H3 is a useful biomarker to determine the pharmacodynamics (PD) activity of AMG 900. FNA biopsies may be a viable approach for assessing AMG 900 PD effects in the clinic.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-014-0307-x) contains supplementary material, which is available to authorized users.

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Serial Biopsies/Fine-Needle Aspirates and Their Assessment

Cited by 6 publications

References 17 publications

PET Imaging of Steroid Hormone Receptor Expression

PET Imaging of Steroid Hormone Receptor Expression

Measurement of conatumumab‐induced apoptotic activity in tumors by fine needle aspirate sampling

AMG 900, a potent inhibitor of aurora kinases causes pharmacodynamic changes in p-Histone H3 immunoreactivity in human tumor xenografts and proliferating mouse tissues

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