• BMB Reports
• /
• v.48 no.3
• /
• pp.127-128
• /
• 2015

Tumor metastasis involves circulating and tumor-initiating capacities of metastatic cancer cells. Hepatic TM4SF5 promotes EMT for malignant growth and migration. Hepatocellular carcinoma (HCC) biomarkers remain unexplored for metastatic potential throughout metastasis. Here, novel TM4SF5/CD44 interaction-mediated self-renewal and circulating tumor cell (CTC) capacities were mechanistically explored. TM4SF5-dependent sphere growth was correlated with $CD133^+$, $CD24^-$, ALDH activity, and a physical association between CD44 and TM4SF5. The TM4SF5/CD44 interaction activated c-Src/STAT3/ Twist1/ B mi1 signaling for spheroid formation, while disturbing the interaction, expression, or activity of any component in this signaling pathway inhibited spheroid formation. In serial xenografts of less than 5,000 cells/injection, TM4SF5-positive tumors exhibited locally-increased CD44 expression, suggesting tumor cell differentiation. TM4SF5-positive cells were identified circulating in blood 4 to 6 weeks after orthotopic liver-injection. Anti-TM4SF reagents blocked their metastasis to distal intestinal organs. Altogether, our results provide evidence that TM4SF5 promotes self-renewal and CTC properties supported by $CD133^+/TM4SF5^+/CD44^+^{(TM4SF5-bound)}/ALDH^+/CD24^-$ markers during HCC metastasis.

• The Korean journal of helicobacter and upper gastrointestinal research
• /
• v.18 no.3
• /
• pp.162-167
• /
• 2018

Cancer specimens obtained via surgical resection or biopsy are generally used to understand tumor-associated alterations; however, those approaches cannot always be performed because of their invasive nature, and they may fail to reflect current tumor dynamics and drug sensitivity, which may change during the therapeutic process. Therefore, many research groups have focused on developing a non-invasive biomarker with the ability to monitor tumor dynamics. Circulating tumor cells (CTCs) are metastatic cells released from the primary tumor into the bloodstream. Hematogenous spreading of CTCs is a crucial step in the metastatic cascade, which leads to the formation of overt metastases. CTCs have attracted considerable attention because of their easy accessibility and their superiority over conventional tumor markers. Detecting CTCs is considered a valuable modality to determine prognosis and monitor response to systemic therapies in patients with gastric cancer. Moreover, molecular analyses of CTCs may provide important biological information for individual patients with cancer, which may lead to the development of personalized cancer treatment. In this article, we review potential roles and clinical applications of CTCs in patients with gastric cancer.

• Journal of Digestive Cancer Reports
• /
• v.8 no.1
• /
• pp.56-60
• /
• 2020

In recent years, liquid biopsy has received immense attention. Liquid biopsy is a minimally invasive method used for obtaining biological fluids including urine, pleural fluid and, mostly, peripheral blood. Liquid biopsy involves various targets including circulating tumors cells (CTCs), circulating cell-free tumor DNA (ctDNA), and microRNA (miRNA). Colorectal cancer (CRC), like other solid tumors, shed tumor cells into the bloodstream. Analysis of these CTCs, as well as ctDNA is the primary objective of the liquid biopsy. Evaluation of CTC or ctDNA offers information about early tumor release, development of tumor metastasis and also about mechanisms involved in tumor resistance to treatment.

• The Korean journal of helicobacter and upper gastrointestinal research
• /
• v.18 no.3
• /
• pp.157-161
• /
• 2018

Liquid biopsy, the analysis of circulating biomarkers from peripheral blood, such as circulating tumor cells (CTCs) and circulating tumor DNA, and exosomes, offers a less invasive, new source of cancer-derived materials that may reflect the status of the disease better and thereby contribute to personalized treatment. Recent advances in microfluidics and molecular analysis technologies have resulted in greatly improved CTC enumeration and detection. In this article, we review commercially available technologies used to isolate CTCs from peripheral blood, including immunoaffinity and label-free, physical property-based isolation methods. Although enormous technological progress has been made, especially within the last decade, only a few CTC detection methods have been approved for routine clinical use. Here, we provide an overview of the current CTC isolation methods and examples of their potential application for early diagnosis, prognosis, treatment monitoring, and prediction of resistance to cancer therapy. Furthermore, the challenges that remain to be addressed before such tools are implemented for routine use in clinical settings are discussed.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.11
• /
• pp.4745-4749
• /
• 2015

Background: The aim of this study was to assess detection of circulating tumor cells (CTC) using anti-CEA pre and post surgery in Chilean patients with colo-rectal cancer. Materials and Methods: The presence of CTCs was evaluated in 80 colorectal cancer patients pre and post surgery using standard immunocytochemistry and the results were compared with findings for standard clinico-pathological parameters. Results: In patients presurgery CEA (+) CTCs were frequently found, with no relation to tumor size or nodal status. After surgery, the presence of CTCs was associated with such clinico-pathological parameters. The frequency of CTC detection in node positive patients did not change after surgery. In patients with metastasis there was also no change in the frequency of CTC detection, and clusters of 3 or more CTCs were evident. Conclusions: Secondary CTCs are associated with clinico-pathological parameters only after surgical removal of the primary tumor, and might be important in identifying patients at high risk of relapse. Primary CTCs detected before surgical removal are frequently found, are not associated with the clinico-pathological parameters and might have a role in cancer screening. These findings suggest the need for studies with a larger population of patients.

• ETRI Journal
• /
• v.37 no.2
• /
• pp.233-240
• /
• 2015

The novelty of this study resides in a 6"-wafer-level microfabrication protocol for a microdevice with a fluidic control system for the separation of circulating tumor cells (CTCs) from human whole blood cells. The microdevice utilizes a lateral magnetophoresis method based on immunomagnetic nanobeads with anti-epithelial cell adhesive molecule antibodies that selectively bind to epithelial cancer cells. The device consists of a top polydimethylsiloxane substrate for microfluidic control and a bottom substrate for lateral magnetophoretic force generation with embedded v-shaped soft magnetic microwires. The microdevice can isolate about 93% of the spiked cancer cells (MCF-7, a breast cancer cell line) at a flow rate of 40/100 mL/min with respect to a whole human blood/buffer solution. For all isolation, it takes only 10 min to process 400 mL of whole human blood. The fabrication method is sufficiently simple and easy, allowing the microdevice to be a mass-producible clinical tool for cancer diagnosis, prognosis, and personalized medicine.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.3
• /
• pp.1725-1729
• /
• 2013

Background: Breast cancer is the second leading cancer causing death in women. Circulating tumor cells are among the prognostic factors while tumor markers are of diagnostic value and can be used for follow-up. The aim of this study was to investigate the correlation between the prognostic significance of the serum CA15-3 levels, number of circulating tumor cells and histopathological tumor factors. Materials and Methods: Thirty patients recently diagnosed with breast cancer were included in the study. Number of circulating tumor cells and serum CA15-3 level were assessed when metastasis was detected and diagnostic value was assessed. Presence of associations with estrogen and progesterone receptors, c-erbB2, Ki-67 proliferation index and histological grade were also evaluated. Results: Median overall survival of the patients with serum CA15-3 levels of >108 ng/dl was 19 months whereas for those with a low serum level it was 62 months. Median overall survival for CTC ${\geq}5$ vs CTC<5 patients was 19 months and 40 months respectively. The difference between the two groups was statistically significant. Conclusions: Prognostic significance of the CTC count and CA15-3 levels in metastatic breast cancer patients was demonstrated.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.19
• /
• pp.8429-8433
• /
• 2014

Circulating tumor cells (CTCs) are believed to be particularly important and a reliable marker of malignancy. However, the prognostic significance of CTCs detected in patients with small cell lung cancer (SCLC) is still unclear. We therefore aimed to assess the prognostic relevance of CTCs using a meta-analysis. We searched PubMed for relevant studies and statistical analyses were conducted to calculate the hazard ratio (HR) and 95% confidence intervals (CIs) using fixed or random-effect models according to the heterogeneity of included studies. A total of 7 papers covering 440 SCLC patients were combined in the final analysis. The meta-analysis revealed that CTCs were significantly associated with shorter overall survival (HR=1.9; 95%CI: 1.19-3.04; Z=2.67; P<0.0001) and progression-free survival (HR=2.6; 95%CI: 1.9-3.54; Z=6.04; P<0.0001). The results thus suggest that the presence of CTCs indicates a poor prognosis in patients with SCLC. Further well-designed prospective studies are required to explore the clinical applications of CTCs in SCLC.

• Journal of Digestive Cancer Research
• /
• v.11 no.1
• /
• pp.21-29
• /
• 2023

Despite recent advancements in the diagnosis and treatment of pancreatic cancer, clinical results remain dismal. Furthermore, there are no reliable biomarkers or alternatives beyond carbohydrate antigen 19-9. Circulating tumor cells (CTCs) may be a potential biomarker, but their therapeutic application is constrained by their rarity in peripheral venous blood. Theoretically, the portal vein can be a more appropriate location for the detection of CTCs, because the first venous drainage of pancreatic cancer is portal circulation. According to several studies, the number and detection rate of CTCs may be higher in the portal blood than in the peripheral blood. CTC counts in the portal blood are strongly correlated with several prognostic parameters such as hepatic metastasis, recurrence after surgery, and survival. The phenotypic and genotypic properties analyzed in the captured portal CTCs can assist us to comprehend tumor heterogeneity and predicting the prognosis of pancreatic cancer. The investigations to date are limited by small sample sizes and varied CTC detection techniques. Therefore, a large number of prospective studies are required to confirm portal CTCs as a valid biomarker in pancreatic cancer.

• Journal of the Korean Society for Precision Engineering
• /
• v.31 no.6
• /
• pp.521-525
• /
• 2014

Circulating tumor cells (CTCs) in the bloodstream of cancer patients provide an accessible source for detection, characterization, and monitoring of nonhematological cancers. The effectiveness of the CTC-Chip for the isolation of ovarian cancer cells was demonstrated by adapting the herringbone-chip (HB-Chip). The motions of the particles on the HB chip were simulated by a unique combination of buoyant, gravitational forces, and helical flows with a computational modeling. The motions of cells are demonstrated by applying polystylene bead and ovarian cancer cells into the microfabricated HB-Chip. The experimental results from beads and cells are well accordance with the simulated ones, as previously reported by Toner group. Thus, I expect that these modeling and experimental skills will play key roles in the clinical applications on CTC isolation as well as the basic research on characterization of CTCs under flow.