• Title, Summary, Keyword: Circulating tumor cells

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Detection of Circulating Tumor Cells in Breast Cancer Patients Using Cytokeratin-19 Real-Time RT-PCR

  • Park, Hyung Seok;Han, Hyun Ju;Lee, Soohyeon;Kim, Gun Min;Park, Seho;Choi, Yeon A;Lee, Jeong Dong;Kim, Gi Moon;Sohn, Joohyuk;Kim, Seung Il
    • Yonsei Medical Journal
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    • v.58 no.1
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    • pp.19-26
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    • 2017
  • Purpose: The roles of circulating tumor cells (CTCs) as predictive and prognostic factors, as well as key mediators in the metastatic cascade, have been investigated. This study aimed to validate a method to quantify CTCs in peripheral blood using a real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay for cytokeratin (CK)-19 and to evaluate the utility of this assay in detecting CTCs in breast cancer patients. Materials and Methods: Real-time monitoring PCR of fluorescently labeled specific hybridization probes for CK-19 mRNA was established. Peripheral blood samples from 30 healthy donors, 69 patients with early breast cancer, 47 patients with locally advanced breast cancer, and 126 patients with metastatic breast cancer were prospectively obtained and analyzed for CTC detection. Results: CK-19 mRNA was not detectable in healthy subjects using the real-time RT-PCR method. The detection rates of CK-19 mRNA in breast cancer patients were 47.8% for early breast cancer (33/69), 46.8% for locally advanced breast cancer (22/47), and 61.1% for metastatic breast cancer (77/129). The detection rate of CK-19-positive CTCs in metastatic disease was slightly higher than early or locally advanced breast cancer; however, the detection rate according to disease burden was not statistically different (p=0.097). The detection rate was higher in patients with pleural metastasis (p=0.045). CTC detection was associated with poor survival (p=0.014). Conclusion: A highly specific and sensitive CK-19 mRNA-based method to detect CTCs in peripheral blood in breast cancer patients can be used in further prospective studies to evaluate the predictive and prognostic importance of CTCs.

Meta-analysis of Circulating Tumor Cells as a Prognostic Marker in Lung Cancer

  • Ma, Xue-Lei;Xiao, Zhi-Lan;Liu, Lei;Liu, Xiao-Xiao;Nie, Wen;Li, Ping;Chen, Nian-Yong;Wei, Yu-Quan
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.4
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    • pp.1137-1144
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    • 2012
  • Introduction: Recent studies have shown that circulating tumor cells (CTCs) play potential roles as diagnostic and prognostic biomarkers with various cancer types. The aim of this study was to comprehensively and quantitatively summarize the evidence for the use of CTCs to predict the survival outcome of lung cancer patients. Materials and Methods: Relevant literature was identified using Medline and EMBASE. Patients' clinical characteristics, overall survival (OS) and progression-free survival (PFS) together with CTC positive rates at different time points (before, during and after treatment) were extracted. A meta-analysis was performed to clarify the prognostic role of CTCs and the correlation between the CTC appearance and clinical characteristics. Results: A total of 12 articles containing survival outcomes and clinical characteristics and 15 articles containing only clinical characteristics were included for the global meta-analysis. The hazard ratio (HR) for OS predicted by pro-treatment CTCs was 2.61 [1.82, 3.74], while the HR for PFS was 2.37 [1.41, 3.99]. The HR for OS predicted by post-treatment CTCs was 4.19 [2.92, 6.00], while the HR for PFS was 4.97 [3.05, 8.11]. Subgroup analyses were conducted according to histological classification and detection method. Odds ratio (OR) showed the appearance of pro-treatment CTCs correlated with the lymph node status, distant metastasis, and TNM staging, while post-treatment CTCs correlated with TNM staging only. Conclusion: Detection of CTCs in the peripheral blood indicates a poor prognosis in patients with lung cancer.

Detection of Circulating Tumor Cells in Breast Cancer Patients: Prognostic Predictive Role

  • Turker, Ibrahim;Uyeturk, Ummugul;Sonmez, Ozlem Uysal;Oksuzoglu, Berna;Helvaci, Kaan;Arslan, Ulku Yalcintas;Budakoglu, Burcin;Alkis, Necati;Aksoy, Sercan;Zengin, Nurullah
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.3
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    • pp.1601-1607
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    • 2013
  • A determination of circulating tumor cell (CTC) effectiveness for prediction of progression-free survival (PFS) and overall survival (OS) was conducted as an adjunct to standard treatment of care in breast cancer management. Between November 2008 and March 2009, 22 metastatic and 12 early stage breast carcinoma patients, admitted to Ankara Oncology Training and Research Hospital, were included in this prospective trial. Patients' characteristics, treatment schedules and survival data were evaluated. CTC was detected twice by CellSearch method before and 9-12 weeks after the initiation of chemotherapy. A cut-off value equal or greater than 5 cells per 7.5 ml blood sample was considered positive. All patients were female. Median ages were 48.0 (range: 29-65) and 52.5 (range: 35-66) in early stage and metastatic subgroups, respectively. CTC was positive in 3 (13.6%) patients before chemotherapy and 6 (27.3%) patients during chemotherapy in the metastatic subgroup whereas positive in only one patient in the early stage subgroup before and during chemotherapy. The median follow-up was 22.0 (range: 21-23) and 19.0 (range: 5-23) months in the early stage and metastatic groups, respectively. In the metastatic group, both median PFS and OS were significantly shorter in any time CTC positive patients compared to CTC negative patients (PFS: 4.0 vs 14.0 months, Log-Rank p=0.013; and OS: 8.0 months vs. 20.5 months, Log-Rank p<0.001). OS was affected from multiple visceral metastatic sites (p=0.055) and higher grade (p=0.044) besides CTC positivity (log rank p<0.001). Radiological response of chemotherapy was also correlated with better survival (p<0.001). As a result, CTC positivity was confirmed as a prospective marker even in a small patient population, in this single center study. Measurement of CTC by CellSearch method in metastatic breast carcinoma cases may allow indications of early risk of relapse or death with even as few as two measurements during a chemotherapy program, but this finding should be confirmed with prospective trials in larger study populations.

Current Status of the Use of Salvaged Blood in Metastatic Spine Tumour Surgery

  • Kumar, Naresh;Ravikumar, Nivetha;Tan, Joel Yong Hao;Akbary, Kutbuddin;Patel, Ravish Shammi;Kannan, Rajesh
    • Neurospine
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    • v.15 no.3
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    • pp.206-215
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    • 2018
  • To review the current status of salvaged blood transfusion (SBT) in metastatic spine tumour surgery (MSTS), with regard to its safety and efficacy, contraindications, and adverse effects. We also aimed to establish that the safety and adverse event profile of SBT is comparable and at least equal to that of allogeneic blood transfusion. MEDLINE and Scopus were used to search for relevant articles, based on keywords such as "cancer surgery," "salvaged blood," and "circulating tumor cells." We found 159 articles, of which 55 were relevant; 20 of those were excluded because they used other blood conservation techniques in addition to cell salvage. Five articles were manually selected from reference lists. In total, 40 articles were reviewed. There is sufficient evidence of the clinical safety of using salvaged blood in oncological surgery. SBT decreases the risk of postoperative infections and tumour recurrence. However, there are some limitations regarding its clinical applications, as it cannot be employed in cases of sepsis. In this review, we established that earlier studies supported the use of salvaged blood from a cell saver in conjunction with a leukocyte depletion filter (LDF). Furthermore, we highlight the recent emergence of sufficient evidence supporting the use of intraoperative cell salvage without an LDF in MSTS.

Characterization of CCND1 and TWIST1 as Prognostic Markers with the Mortality Rate of Breast Cancer

  • Ahn, Sungwoo;Park, Sangjung;Wang, Hye-Young;Park, Sunyoung;Kim, Jungho;Lee, Hyeyoung
    • Biomedical Science Letters
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    • v.24 no.2
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    • pp.76-86
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    • 2018
  • Breast cancer is one of the most common cancers affecting women worldwide. Although the survival rate of breast cancer has increased, breast cancer still results in a high mortality rate. Breast cancer deaths are caused by metastasis that occurs in organ dysfunction. Recently, there have been many studies on circulating tumor cells (CTCs), which are related to breast cancer metastasis in the blood. Recent studies have demonstrated that some CTCs do not express epithelial markers. Therefore, in this study, total RNA was extracted from blood without separating out the CTCs, and the characteristics of the CTCs were analyzed by RT-qPCR. Cyclin D1 and twist-related protein 1 (TWIST1) are well-known markers for predicting the prognosis of patients with breast cancer. However, few studies have demonstrated the use of CCND1 and TWIST1 in blood as diagnostic and prognostic markers of breast cancer. In this study, patients with late-stage breast cancer had overexpressed CCND1 and TWIST1 than patients with different stages of breast cancer (P < 0.001 and P < 0.01, respectively). The relative expression level of CCND1 in survivors was higher than in patients who died (P = 0.06). The relative expression level of TWIST1 in survivors was lower than in patients who died (P = 0.08). Overall CCND1 and TWIST1 were not useful as markers for the diagnosis of breast cancer through blood. However, we showed the possibility of using CCND1 and TWIST1 as prognostic markers, and a large-scale study is needed to confirm the usefulness of these prognostic markers.

Prognostic Role of Circulating Tumor Cells in Patients with Pancreatic Cancer: a Meta-analysis

  • Ma, Xue-Lei;Li, Yan-Yan;Zhang, Jing;Huang, Jing-Wen;Jia, Hong-Yuan;Liu, Lei;Li, Ping
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.15
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    • pp.6015-6020
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    • 2014
  • Background: Isolation and characterization of circulating tumor cells (CTCs) in patients suffering from a variety of different cancers have become hot biomarker topics. In this study, we evaluated the prognostic value of CTCs in pancreatic cancer. Materials and Methods: Initial literature was identified using Medline and EMBASE. The primary data were hazard ratios (HRs) with 95% confidence intervals (CIs) of survival outcomes, including overall survival (OS) and progression free survival/recurrence free survival (PFS/RFS). Results: A total of 9 eligible studies were included in this meta-analysis, published between 2002 and 2013. The estimated pooled HR and 95%CI for OS for all studies was 1.64 (95%CI 1.39-1.94, p<0.00001) and the pooled HR and 95%CI for RFS/DFS was 2.36 (95%CI 1.41-3.96, p<0.00001). The HRs and 95%CIs for OS and RFS/DFS in patients before treatment were 1.93 (95%CI 1.26-2.96, p=0.003) and 1.82 (95%CI 1.22-2.72, p=0.003), respectively. In patients receiving treatment, the HRs and 95%CI for OS and RFS/DFS were 1.37 (95%CI 1.00-1.86, p=0.05) and 1.89 (95%CI 1.01-3.51, p=0.05), respectively. Moreover, the pooled HR and 95%CI for OS in the post-treatment group was 2.20 (95%CI 0.80-6.02, p=0.13) and the pooled HR for RFS/DFS was 8.36 (95%CI 3.22-21.67, p<0.0001). Conclusions: The meta-analysis provided strong evidence supporting the proposition that CTCs detected in peripheral blood have a fine predictive role in pancreatic patients especially on the time point of post-treatment.

Nodal tumor response according to the count of peripheral blood lymphocyte subpopulations during preoperative chemoradiotherapy in locally advanced rectal cancer

  • Heo, Jaesung;Oh, Young-Taek;Noh, O Kyu;Chun, Mison;Park, Jun-Eun;Cho, Sung-Ran
    • Radiation Oncology Journal
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    • v.34 no.4
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    • pp.305-312
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    • 2016
  • Purpose: The objective of this prospective study was to evaluate the relationship between the circulating lymphocyte subpopulation counts during preoperative chemoradiotherapy (CRT) and tumor response in locally advanced rectal cancer. Materials and Methods: From August 2015 to June 2016, 10 patients treated with preoperative CRT followed by surgery were enrolled. Patients received conventional fractionated radiotherapy (50.4 Gy) with fluorouracil-based chemotherapy. Surgical resection was performed at 4 to 8 weeks after the completion of preoperative CRT. The absolute blood lymphocyte subpopulation was obtained prior to and after 4 weeks of CRT. We analyzed the association between a tumor response and change in the lymphocyte subpopulation during CRT. Results: Among 10 patients, 2 (20%) had evidence of pathologic complete response. In 8 patients with clinically node positive, 4 (50%) had nodal tumor response. All lymphocyte subpopulation counts at 4 weeks after CRT were significantly lower than those observed during pretreatment (p < 0.01). A high decrease in natural killer (NK) cell, count during CRT (baseline cell count - cell count at 4 weeks) was associated with node down staging (p = 0.034). Conclusion: Our results suggest that the change of lymphocyte subset to preoperative CRT may be a predictive factor for tumor response in rectal cancer.

Immunopotentiating and Antitumor Activities of Purified pectins and Polysaccharides from Trichosnnthes Rhizoma and Taraxii Herba

  • Park, Soo-Wan;Chung, Yeoun-Bong;Kim, Hye-Kyung;Lee, Chung-Kyu
    • Biomolecules & Therapeutics
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    • v.2 no.2
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    • pp.126-130
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    • 1994
  • Water-soluble pectins isolated from Trichosanthes Rhizoma and Taraxii Herba and their deproteinized polysaccharides were purified through DEAE cellulose column and were applied to immunopotentiating and antitumor studies to clarify the nature of their activities of our previous reports. As the results of works, the lectins and deproteinized polysaccharides increased the number of circulating leukocytes and total peritoneal cells. And they markedly elevated the lowered production of antibody and reactivity of T Iymphocyte in tumor-bearing mice, which were rapidly recovered by discontinuance of sample treatments. They also decreased the growth of Sarcoma 180 solid tumor in mice.

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Inhibitory activities of polysaccharide purified from Phellodendron chinese SCHNEID on melanoma B-16-derived metastatic tumor and hypersensitivity

  • Kim, June-Ki;Kim, Sung-Soo;Jun, Kyun-Il;Lee, Dong-Young;Lee, Tae-Kyun;Song, Eun-Young;Kim, Cheorl-Ho
    • Oriental Pharmacy and Experimental Medicine
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    • v.1 no.2
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    • pp.36-44
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    • 2000
  • The polysaccharide fractions were isolated and purified from Phellodendron chinese SCHNEID, and antitumor activities using the melanoma B-16-derived metastatic tumors were examined at dosages of 2, 5 and 10 mg/100 g. F-7 and F-8 showed the highest tumor metastatic inhibitory activities (inhibition ratio 60 and 80% in 2 mg/100 g), and in dose of 5 mg/100 g, the inhibitory ratios were 85 and 70%, respectively. Furthermore, 10 mg/100 g of intraperitoneal (i.p.) injection gave 90 and 95% of inhibition. When the effects of polysaccharides on hypersensitivity were examined, the inhibitory activities were not markedly observed in oral administration, indicating that the polysaccharides are directly acting to immune system. Also, the polysaccharides increased the number of circulating blood leukocytes and total peritoneal exudate cells. Although implantation of tumor cells greatly decreased the productivity of antibody (antibody-mediated) and T lymphocyte reactivity (delayed-type) as 6.3 from 9.3 and 5.9 from 7.7, represented by the increase of footpad thickness, respectively. the polysaccharides elevated the reactivity of T lymphocyte in tumor-bearing mice, which were rapidly recovered by discontinuance of sample treatments. Especially, F-2, F-5, F-7 and F-8 remarkably recovered the decreased sensitivity. These results clearly indicated that the i.p. injection is much effective to suppress tumor growth than oral administration.

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Dietary Ziziphus jujuba Fruit Influence on Aberrant Crypt Formation and Blood Cells in Colitis-Associated Colorectal Cancer Mice

  • Periasamy, Srinivasan;Liu, Chung-Teng;Wu, Wang-Hung;Chien, Se-Ping;Liu, Ming-Yie
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.17
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    • pp.7561-7566
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    • 2015
  • Ziziphus jujuba (ZJ) fruit is rich in bioactive functional components such as polysaccharides, triterpenoid acid, flavonoids and oleamide. It has been commonly used in the treatment of various diseases including diabetes, digestive disorders, diarrhea, skin infections, liver and urinary diseases. However, its dietary effect on chemoprevention of colon cancer has never been studied. The present study was to evaluate the protective effects of dietary ZJ on colitis-associated colon carcinogenesis in azoxymethane (AOM)-dextran sodium sulphate (DSS)-treated mice. AOM was injected (10 mg/kg b.wt., i.p.) and three cycles of 2% DSS in drinking water for 7 days with 14 days of normal drinking water in-between was administered to induce colitis-associated colon cancer. ZJ fruit was supplemented in feed as 5 and 10%. Dietary ZJ significantly attenuated aberrant crypt foci (ACF) formation thereby decreasing the progression of hyperplasia to dysplasia. In addition, it significantly reduced circulating white blood cells, lymphocytes, neutrophils, monocytes, eosinophils, basophils and platelets compared to colon cancer mice. We conclude that ZJ supplementation delayed the progression of colon cancer from hyperplasia to dysplasia and ultimately adenocarcinoma and cancer. In addition, it decreased circulating tumor-related leucocytes, main regulators of cancer inflammation. Therefore, dietary consumption of ZJ fruit attenuated the formation of ACF and delayed the progression of colon cancer.