Improving antitumor efficacy of PEGylated liposomal doxorubicin by dual targeting of tumor cells and tumor endothelial cells using anti-p32 CGKRK peptide

5551 Background: Circulating tumor cells (CTC) have demonstrated predictive and prognostic value among patients with metastatic breast, colorectal, and prostate cancer. In a phase III study of pegylated liposomal doxorubicin (PLD) with trabectedin (T) vs PLD for relapsed ovarian cancer, we assessed the affect of CTCs on progression free survival, (PFS) and overall survival (OS). Methods: CTCs were isolated from peripheral blood (10 mLs) using the CellSearch system and reagents (Veridex). A CTC is defined as EpCAM+, cytokeratin+, CD45-, and is positive for the nuclear stain DAPI. The normal reference range for CellSearch is < 2 CTC/7.5 mLs of blood. Hazard ratios adjusted for known prognostic factors were estimated by Cox regression. Results: 216 subjects had baseline CTC measurements of which 111 (51.4%) were randomized to the PLD+T arm; 143/216 patients (66.2%) were platinum sensitive. Thirty-one/216 patients (14.4%) had 2 or more CTCs detected prior to the start of therapy (range 2–566). Univariate Cox regression analyses indicated that patient's > 2 CTCs prior to therapy have 1.89 (p = 0.003) and 2.06 (p = 0.003) fold higher risk for progression and death respectively. Multivariate analyses that include baseline CTC, baseline CA125, platinum sensitivity status, largest diameter lesion, number of tumor lesions, ECOG PS, age, tumor histology, tumor grade and prior taxane show that patients with elevated baseline CTC have 1.58 (p = 0.058) and 1.54 (p = 0.096) fold higher risk for progression and death respectively. Conclusions: Results from this study indicate that although CTC detection in blood from relapsed recurrent ovarian cancer patients is relatively low, elevated numbers of CTCs imparts an unfavorable prognosis for patients. Multivariate analysis indicates that CTCs have prognostic value that is independent of established factors and thus provides a clinically useful tool for assessing prognosis in this difficult to treat patient population. [Table: see text]

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Optimizing Antitumor Efficacy and Adverse Effects of Pegylated Liposomal Doxorubicin by Scheduled Plasmapheresis: Impact of Timing and Dosing

Current Drug Delivery ◽

10.2174/1567201815666180518125839 ◽

2018 ◽

Vol 15 (9) ◽

pp. 1261-1270 ◽

Cited By ~ 4

Author(s):

Romeo Ngoune ◽

Christine Contini ◽

Michael M. Hoffmann ◽

Dominik von Elverfeldt ◽

Karl Winkler ◽

...

Keyword(s):

Adverse Effects ◽

Liposomal Doxorubicin ◽

Pegylated Liposomal Doxorubicin ◽

Antitumor Efficacy

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Dual targeting of Raf and VEGF receptor 2 reduces growth and metastasis of pancreatic cancer through direct effects on tumor cells, endothelial cells, and pericytes

Molecular Cancer Therapeutics ◽

10.1158/1535-7163.mct-08-0373 ◽

2008 ◽

Vol 7 (11) ◽

pp. 3509-3518 ◽

Cited By ~ 32

Author(s):

Sven A. Lang ◽

Philipp Schachtschneider ◽

Christian Moser ◽

Akira Mori ◽

Christina Hackl ◽

...

Keyword(s):

Pancreatic Cancer ◽

Endothelial Cells ◽

Tumor Cells ◽

Vegf Receptor ◽

Direct Effects ◽

Dual Targeting

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Aneuploid circulating tumor endothelial cells (CTECs) affect the detection of CTC, but they are fundamentally different

10.21203/rs.3.rs-25021/v1 ◽

2020 ◽

Author(s):

Yuanyuan Lei ◽

Guochao Zhang ◽

Chengming Liu ◽

Zhiliang Lu ◽

Jianbing Huang ◽

...

Keyword(s):

Endothelial Cells ◽

Tumor Cells ◽

Clinical Significance ◽

Traditional Method ◽

Detection Method ◽

Detection Methods ◽

Lung Cancer Patients ◽

Tumor Endothelial Cells ◽

Benign Nodules ◽

Combined Detection

Abstract Background Aneuploidy is an important criterion for tumor cell identification. Like CTCs (circulating tumor cells), many CTECs (circulating tumor endothelial cells) have chromosomal aneuploidy. Affected by tumor microenvironment and detection method, the only identification index CD31 may not be comprehensive enough, which greatly affects the accuracy of CTCs detection. Methods Here, we explored the number distribution, expression of surface tumor markers and chromosome ploidy differences of aneuploid CTECs and CTCs in a total of 98 peripheral blood from normal volunteers, benign nodules and lung cancer patients, trying to find the differences between the two and the clinical significance of CTEC. Results We found that CTCs were mainly dominated by triploid and hyperploid (pentaploid or above), The former was mainly small CTCs, and the latter was mainly large CTCs. While the aneuploid CTECs were mostly large tetraploid cells. Combined detection of total CTC and CTEC numbers helped identify benign and malignant nodules. Furthermore, tetraploid CTC and CTEC had more obvious advantages than other ploids in identifying benign and malignant nodules. Conclusions Our findings indicated that the traditional method of distinguishing tumor and non-tumor cells by aneuploidy was not accurate. The presence of aneuploidy CTECs greatly interfered with the detection of CTCs, but they were different form CTC in cell size, chromosome ploidy distribution and had certain clinical significance. Combining CTC and CTEC had better diagnostic advantages

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Optimal Strategy for Colorectal Cancer Patients’ Diagnosis Based on Circulating Tumor Cells and Circulating Tumor Endothelial Cells by Subtraction Enrichment and Immunostaining-Fluorescence In Situ Hybridization Combining with CEA and CA19-9

Journal of Oncology ◽

10.1155/2021/1517488 ◽

2021 ◽

Vol 2021 ◽

pp. 1-9

Author(s):

Shimu Luo ◽

Yanghang Ou ◽

Tingjin Zheng ◽

Huihui Jiang ◽

Yibo Wu ◽

...

Keyword(s):

Colorectal Cancer ◽

Endothelial Cells ◽

Logistic Regression ◽

In Situ Hybridization ◽

Fluorescence In Situ Hybridization ◽

Tumor Cells ◽

Roc Curve ◽

Healthy Controls ◽

Tumor Endothelial Cells

Background. Cancerous embryo antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) are commonly used in clinical practice to assist in diagnosing CRC. However, their sensitivity is very low. This study aims to investigate the clinical significance of circulating tumor cells (CTCs) and circulating tumor endothelial cells (CTECs) compared with CEA and CA19-9 in the auxiliary diagnosis of colorectal cancer (CRC) patients. Methods. 115 pathologically confirmed CRC patients and 20 healthy controls were enrolled in this study. CTCs and CTECs were enriched and identified by subtraction enrichment and immunostaining-fluorescence in situ hybridization (SE-iFISH). A logistic regression was used to establish a model for the receiver-operating characteristic (ROC) curve analysis, and the diagnostic efficacy of CTCs, CTECs, CEA, CA19-9, and their combinations was analyzed. Results. The CTC ( P < 0.0001 ) and CTEC ( P = 0.0009 ) level was significantly higher in CRC patients than that in healthy controls. For CRC patients, CTC and CTEC level was significantly correlated with tumor stage and lymph node metastasis status, but not with sex, age, tumor location, and degree of differentiation. The positive rate of CTCs, CTECs, CEA, and CA19-9 in CRC patients was 87.8%, 39.1%, 28.7%, and 26.1%, respectively. To distinguish CRC patients from controls, the area under the curve (AUC) of CTC was 0.889, which was much higher than 0.695 of CTEC, 0.696 of CEA, and 0.695 of CA19-9. Establishing ROC curve by logistic regression algorithm, the highest AUC was 0.935, which combined CTCs with CTEC, CEA, and CA19-9. Conclusions. CTCs combined with CTEC, CEA, and CA19-9 are useful to improve the diagnostic efficiency, which has high clinical significance in the diagnosis of colorectal cancer.

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