Prognostic impact of detecting viable circulating tumour cells in gastric cancer patients using a telomerase-specific viral agent: a prospective study

Ito, Hiroaki; Inoue, Haruhiro; Sando, Norimasa; Kimura, Satoshi; Gohda, Keigo; Sato, Jun; Murakami, Katsuhiro; Ito, Shun; Odaka, Noriko; Satodate, Hitoshi; Kudo, Shin‐ei

doi:10.1186/1471-2407-12-346

Cited by 38 publications

(46 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Details of sample preparation and assay are described in our previous report (23). A 7.5-ml peripheral vein blood sample was obtained from each patient before surgery and at 4 and 24 weeks after surgery.…”

Section: Methodsmentioning

confidence: 99%

“…The threshold for GFP fluorescence intensity was determined as previously reported (23). Briefly, blood samples (7.5 ml) from healthy volunteers were mixed with ~30,000 A549 (lung carcinoma), HepG2 (hepatocellular carcinoma), HEC-1 (endometrial carcinoma), KATO-III (gastric carcinoma), SBC-3 (small cell lung carcinoma), LNCaP (prostate adenocarcinoma), MDA-MB-468 (breast carcinoma) or OVCAR-3 (ovarian carcinoma) cells.…”

Section: Methodsmentioning

confidence: 99%

“…Gastric cancer is the fifth most common cancer worldwide and the third most frequent cause of cancer-associated mortality, affecting ~723,000 people in 2012 (24). In that study, blood samples from 65 treatment-naïve gastric cancer patients were collected prior to surgery (23). CTCs are larger than normal blood cells (25,26), and it was observed that the GFP+ cells in these samples with a diameter ≥7.735 µm (termed L-GTP+ cells) expressed EpCAM and other CTC markers (23).…”

Section: Introductionmentioning

confidence: 99%

“…In that study, blood samples from 65 treatment-naïve gastric cancer patients were collected prior to surgery (23). CTCs are larger than normal blood cells (25,26), and it was observed that the GFP+ cells in these samples with a diameter ≥7.735 µm (termed L-GTP+ cells) expressed EpCAM and other CTC markers (23). Additional results indicated that the number of L-GFP+ cells was significantly correlated with venous invasion (23) and overall survival after a median follow-up period of 3 years (27).…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

et al. 2016

Self Cite

View full text Add to dashboard Cite

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...

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…[63] 2011 98 RT-PCR, ELISA Survivin The detection of CTCs expressing survivin mRNA was an independent prognostic factors of DFS Ito et al . [64] 2012 65 ICC GFP, EpCAM There was a significant relationship between the number of GFP-positive CTCs and overall survival Arigami et al . [65] 2013 93 RT-PCR STC2 The 5-year OS rate was significantly lower in patients with STC2 expressioncompared to patients without STC2 expression Uenosono et al .…”

Section: Heterogeneity Of Ctcsmentioning

confidence: 99%

Circulating tumor cells in gastric cancer

Nakamura¹,

Iwatsuki²,

Kurashige³

et al. 2018

JCMT

View full text Add to dashboard Cite

Circulating tumor cells (CTCs) have received a lot of attention as a novel biomarker for cancer research in past decades. CTCs infiltrate the bloodstream derived from the primary tumor, and are significantly involved in cancer metastasis and recurrence. Although clinical applications have been challenging owing to the difficulties of CTC identification, recent development of technology for specific enrichment and detection of CTCs contributes to diagnosis and treatment. Furthermore, CTC analyses will shed new light on the biological mechanisms of cancer progression and metastasis. A number of clinical studies have already been carried out on the basis of CTC technology. Nevertheless, the clinical utility of CTCs is still unknown in gastric cancer. In this review, we elaborate on the latest advances of CTC research in gastric cancer.

show abstract

Clinical significance of circulating tumor cells in blood from patients with gastric cancer

Arigami

Uenosono

Yanagita

et al. 2017

Annals of Gastroent Surgery

View full text Add to dashboard Cite

Circulating tumor cells (CTC) have been focused on as a target for detecting occult tumors, predicting therapeutic responses and prognoses, and monitoring postoperative recurrence in the clinical management of patients with various malignancies, including gastric cancer. Recent advances in molecular diagnostic tools have contributed to high sensitivity and specificity for the detection of CTC. A conspicuous disparity exists in the incidence of CTC among studies. However, a close relationship has been reported between positivity for CTC and well‐known prognostic clinicopathological factors including depth of tumor invasion, lymph node metastasis, stage, and lymphatic and venous invasion in patients with gastric cancer. According to most studies published on the clinical impact of CTC, the presence of CTC negatively affects the prognosis of patients with gastric cancer. Moreover, the study of CTC based on a meta‐analysis demonstrated their importance as a poor prognostic indicator. In clinical management, pre‐ and post‐therapeutic monitoring of CTC using liquid biopsy may be useful for early detection of subclinical patients or disease recurrence, prediction of tumor progression, and administrative control of adjuvant chemotherapy. Although their functional properties remain unclear, molecular profiling of CTC may contribute to the development of personalized treatment that effectively inhibits tumor progression in patients with advanced gastric cancer. We herein review the clinical significance of CTC as a promising blood marker and therapeutic target in patients with gastric cancer.

show abstract

Prognostic impact of detecting viable circulating tumour cells in gastric cancer patients using a telomerase-specific viral agent: a prospective study

Cited by 38 publications

References 34 publications

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

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

Circulating tumor cells in gastric cancer

Clinical significance of circulating tumor cells in blood from patients with gastric cancer

Contact Info

Product

Resources

About