Change in number and size of circulating tumor cells with high telomerase activity during treatment of patients with gastric cancer

Abstract

Abstract. Detection of circulating tumor cells (CTCs) in peripheral blood is useful for estimating the prognosis of patients with cancer. We previously reported the detection of CTCs by OBP-401, a telomerase-specific, replication-selective, oncolytic adenoviral agent carrying the green fluorescent protein (GFP) gene. We demonstrated that the number of large (L)-GFP+ cells (≥7.735 µm in diameter) in peripheral blood samples correlated significantly with the prognosis of treatment-naïve gastric cancer patients, whereas the number of small (S)-GFP+ cells (<7.735 µm in diameter) did not. In the present study, we studied the change in the number of GFP+ cells during treatment, and analyzed the association between the number of GFP+ cells in blood samples and the outcome of patients. Peripheral blood samples were obtained from 37 gastric patients prior and subsequent to surgery (three samples per time point). Upon infection of blood cells with OBP-401, GFP+ cells of different sizes were counted and measured. The association between the number of GFP+ cells and surgical outcome was determined by statistical analysis. The median follow-up period after surgery was 39 months. Although the difference was not significant, patients with ≥6 L-GFP+ cells in preoperative blood samples had a lower relapse-free survival rate than patients with 0-5 L-GFP+ cells. There was no significant correlation between the number of L-GFP+ cells in postoperative blood samples and the prognosis of patients receiving adjuvant therapy. Although the difference was not significant, the number of S-GFP+ cells in samples from patients who had received postoperative chemotherapy was higher than in those who had not. The number of L-GFP+ cells was not significantly correlated with the relapse-free survival rate in gastric cancer patients who underwent surgery. The number of S-GFP+ cells was relatively high in samples from patients who had received postoperative chemotherapy. IntroductionThe presence of circulating tumor cells (CTCs) in peripheral blood indicates a systemic disease stage (1), and detection of CTCs in peripheral blood is useful for estimating prognosis and monitoring disease progression in breast (2), prostate (3), skin (4) and colon (5) malignancies. The commonly used techniques for enrichment and detection of CTCs are density gradient separation (6,7), direct enrichment by filtration (8), immunomagnetic separation (9), flow cytometry (10), reverse transcription-polymerase chain reaction (RT-PCR) (11,12) and microchip technology (13). The CELLSEARCH ® System (Veridex LLC, Raritan, NJ, USA) (14) is a widely used automated method of immunomagnetic cell enrichment (15-17) that detects CTCs by detection of epithelial markers such as epithelial cell adhesion molecule (EpCAM) and cytokeratin. The expression of these markers, however, decreases during the epithelial-mesenchymal transition (EMT) (18,19); thus, CTCs undergoing EMT may escape detection.Increased telomerase activity is a common characteristic of malignant tumors, and telomerase ac...

Vimentin expression in circulating tumor cells (CTCs) associated with liver metastases predicts poor progression-free survival in patients with advanced lung cancer

“…Moreover, pretreatment small cell CTCs (≥ 2/6 ml) were highly related to poor prognosis in advanced lung cancer patients. Though previous studies have documented the mesenchymal CTCs or CTCs in patients following therapeutic treatment were in small cell size (Hiroaki et al 2014; Ito et al 2016), few studies have been conducted to further investigate how diverse CTCs based on cell size correlate to clinical outcome due to the inherent drawbacks of the conventional CTCs technology. As far as we know, it is the first time in our study to report the dynamic change of small cell CTCs number correlated to treatment response and pretreatment small cell CTCs (≥ 2/6 ml) were significantly related to unfavorable clinical outcome in advanced lung cancer patients.…”

Separation of cancer cells using vortical microfluidic flows

“…We also point out that the size distribution of the cultured cells might be different than actual tumor cells circulating in the blood, which can vary specially during treatment of patients. 28 We present our results in the following order: In Sec. IV, we discuss the breakdown of the separatrix.…”

Heterogeneous circulating tumor cells correlate with responses to neoadjuvant chemotherapy and prognosis in patients with locally advanced breast cancer

“…Complementary techniques such as ISET (isolation by size of epithelial tumor cells), based on a direct size selection method for epithelial cell enrichment to further lter small CTCs may be applied to generate additional information. Research has shown the number of small CTCs is increased following chemotherapy and is accompanied by the increased ratio of drug-resistant to drug-sensitive CTCs [44]. CTMs, derived from oligoclonal groups of cells from the primary tumor, have a 23-to 50-fold increased metastatic potential compared to single CTCs [45].…”