Early Detection and Dynamic Changes of Circulating Tumor Cells in Transgenic NeuN Transgenic (NTTg) Mice with Spontaneous Breast Tumor Development

Background: This study used NeuN transgenic (NTTg) mice with spontaneous breast tumor development to evaluate the dynamic changes of circulating tumor cells (CTCs) prior to and during tumor development. Methods: In this longitudinal, clinically uninterrupted study, we collected 75 μL of peripheral blood at the age of 8, 12, 16, and 20 weeks in the first group of five mice, and at the age of 32 weeks, the time of tumor palpability, and one week after tumor palpability in the second group of four mice. Diluted blood samples were run through a modified mouse-CMx chip to isolate the CTCs. Results: The CTC counts of the first group of mice were low (1 ± 1.6) initially. The average CTC counts were 16 ± 9.5, 29.0 ± 18.2, and 70.0 ± 30.3 cells per 75 μL blood at the age of 32 weeks, the time of tumor palpability, and one week after tumor palpability, respectively. There was a significant positive correlation between an increase in CTC levels and tumor vascular density (p-value < 0.01). This correlation was stronger than that between CTC levels and tumor size (p-value = 0.076). The captured CTCs were implanted into a non-tumor-bearing NTTg mouse for xenografting, confirming their viability and tumorigenesis. Conclusion: Serial CTCs during an early stage of tumor progression were quantified and found to be positively correlated with the later tumor vascular density and size. Furthermore, the successful generation of CTC-derived xenografts indicates the tumorigenicity of this early onset CTC population.

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FlowCell-enriched circulating tumor cells as a predictor of lung cancer metastasis

Human Cell ◽

10.1007/s13577-021-00500-8 ◽

2021 ◽

Author(s):

Yan Lu ◽

Yushuang Zheng ◽

Yuhong Wang ◽

Dongmei Gu ◽

Jun Zhang ◽

...

Keyword(s):

Lung Cancer ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Cancer Metastasis ◽

Lung Tumor ◽

Early Stage ◽

High Rate ◽

Early Stage Lung Cancer ◽

Lung Cancer Metastasis ◽

Number Of Patients

AbstractLung cancer is the most fetal malignancy due to the high rate of metastasis and recurrence after treatment. A considerable number of patients with early-stage lung cancer relapse due to overlooked distant metastasis. Circulating tumor cells (CTCs) are tumor cells in blood circulation that originated from primary or metastatic sites, and it has been shown that CTCs are critical for metastasis and prognosis in various type of cancers. Here, we employed novel method to capture, isolate and classify CTC with FlowCell system and analyzed the CTCs from a cohort of 302 individuals. Our results illustrated that FlowCell-enriched CTCs effectively differentiated benign and malignant lung tumor and the total CTC counts increased as the tumor developed. More importantly, we showed that CTCs displayed superior sensitivity and specificity to predict lung cancer metastasis in comparison to conventional circulating biomarkers. Taken together, our data suggested CTCs can be used to assist the diagnosis of lung cancer as well as predict lung cancer metastasis. These findings provide an alternative means to screen early-stage metastasis.

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Clinical significance of circulating tumor cells and metabolic signatures in lung cancer after surgical removal

10.21203/rs.3.rs-17157/v1 ◽

2020 ◽

Author(s):

Dawei Yang ◽

Xiaofang Yang ◽

Yang Li ◽

Peige Zhao ◽

Rao Fu ◽

...

Keyword(s):

Lung Cancer ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Early Stage ◽

Effective Means ◽

Disease Recurrence ◽

Metabolic Changes ◽

Surgical Removal ◽

Targeted Metabolomics ◽

Post Surgery

Abstract Background Lung cancer (LC) remains the deadliest form of cancer globally. While surgery remains the optimal treatment strategy for individuals with early-stage LC, what the metabolic consequences are of such surgical intervention remains uncertain. Methods Negative enrichment-fluorescence in situ hybridization (NE-FISH) was used in an effort to detect circulating tumor cells (CTCs) in pre- and post-surgery peripheral blood samples from 51 LC patients. In addition, targeted metabolomics analyses, multivariate statistical analyses, and pathway analyses were used to explore surgery-associated metabolic changes. Results LC patients had significantly higher CTC counts relative to healthy controls with 66.67% of LC patients having at least 1 detected CTC. CTC counts were associated with clinical outcomes following surgery. In a targeted metabolomics analysis, we detected 34 amino acids, 164 lipids, and 24 fatty acids. When comparing LC patients before and after surgery to control patients, metabolic shifts were detected via PLS-DA and pathway analysis. Further surgery-associated metabolic changes were identified when comparing LA and LB groups. We identified SM 42:4, Ser, Sar, Gln, and LPC 18:0 for inclusion in a biomarker panel for early-stage LC detection based upon an AUC of 0.965 (95% CI = 0.900–1.000). This analysis revealed that SM 42:2, SM 35:1, PC (16:0/14:0), PC (14:0/16:1), Cer (d18:1/24:1), and SM 38:3 may offer diagnostic and prognostic benefits in LC. Conclusions These findings suggest that CTC detection and plasma metabolite profiling may be an effective means of diagnosing early-stage LC and identifying patients at risk for disease recurrence.

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Dynamic Changes in Numbers and Properties of Circulating Tumor Cells and Their Potential Applications

Cancers ◽

10.3390/cancers6042369 ◽

2014 ◽

Vol 6 (4) ◽

pp. 2369-2386 ◽

Cited By ~ 17

Author(s):

Ju-Yu Tseng ◽

Chih-Yung Yang ◽

Shu-Ching Liang ◽

Ren-Shyan Liu ◽

Jeng-Kai Jiang ◽

...

Keyword(s):

Tumor Cells ◽

Circulating Tumor Cells ◽

Dynamic Changes ◽

Potential Applications

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Clinical Impact of Circulating Tumor Cells in Patients with Localized Prostate Cancer

Cells ◽

10.3390/cells8070676 ◽

2019 ◽

Vol 8 (7) ◽

pp. 676 ◽

Cited By ~ 11

Author(s):

Broncy ◽

Paterlini-Bréchot

Keyword(s):

Prostate Cancer ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Early Stage ◽

Clinical Impact ◽

Localized Prostate Cancer ◽

Aggressive Cancer ◽

Highly Sensitive ◽

Prostate Cancers ◽

Suitable Marker

The main issue concerning localized prostate cancers is the lack of a suitable marker which could help patients’ stratification at diagnosis and distinguish those with a benign disease from patients with a more aggressive cancer. Circulating Tumor Cells (CTC) are spread in the blood by invasive tumors and could be the ideal marker in this setting. Therefore, we have compiled data from the literature in order to obtain clues about the clinical impact of CTC in patients with localized prostate cancer. Forty-three publications have been found reporting analyses of CTC in patients with non-metastatic prostate cancer. Of these, we have made a further selection of 11 studies targeting patients with clinical or pathological stages T1 and T2 and reporting the clinical impact of CTC. The results of this search show encouraging data toward the use of CTC in patients with early-stage cancer. However, they also highlight the lack of standardized methods providing a highly sensitive and specific approach for the detection of prostate-derived CTC.

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Abstract P2-01-14: circulating tumor cells in breast cancer exhibit dynamic changes in epithelial and mesenchymal cell composition

10.1158/0008-5472.sabcs12-p2-01-14 ◽

2012 ◽

Author(s):

M Yu ◽

A Bardia ◽

BS Wittner ◽

SL Stott ◽

ME Smas ◽

...

Keyword(s):

Breast Cancer ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Mesenchymal Cell ◽

Dynamic Changes ◽

Cell Composition

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Abstract LB-286: Use of circulating tumor cells to monitor pharmacodynamic responses of patients in early-stage clinical trials

10.1158/1538-7445.am10-lb-286 ◽

2010 ◽

Cited By ~ 1

Author(s):

Robert J. Kinders ◽

Lihua Wang ◽

Shivaani Kummar ◽

Thomas Pfister ◽

Ralph Parchment ◽

...

Keyword(s):

Clinical Trials ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Early Stage

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Abstract 2039: Dynamic changes and regulation of circulating tumor cells that govern the metastasis of colorectal cancer

10.1158/1538-7445.am2014-2039 ◽

2014 ◽

Author(s):

Ju-Yu Tseng ◽

Chih-Yung Yang ◽

Jeng-Kai Jiang ◽

Chi-Hung Lin

Keyword(s):

Colorectal Cancer ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Dynamic Changes

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Immunoprotective Effect of Cu/Zn Superoxide Dismutase on Myeloid Graffi Tumor-Bearing Hamsters

Zeitschrift für Naturforschung C ◽

10.1515/znc-2000-7-826 ◽

2000 ◽

Vol 55 (7-8) ◽

pp. 649-656 ◽

Cited By ~ 2

Author(s):

Reneta A. Toshkova ◽

Petia A. Dimitrova ◽

Emilia H. Ivanova ◽

Pavlina A. Dolashka ◽

Maria B. Angelova ◽

...

Keyword(s):

Superoxide Dismutase ◽

Tumor Growth ◽

Protective Effect ◽

Phagocytic Activity ◽

Tumor Antigens ◽

Early Stage ◽

Tumor Development ◽

Peritoneal Macrophages ◽

Tumor Bearing

Abstract Investigation on the immunoprotective activity of Cu/Zn superoxide dismutase from Humicola lutea 103 AL (HLSOD) in hamsters with transplanted myeloid tumor was performed. Survivability, tumor growth and tumor transplantability were followed. The immune status of tumor-bearing animals, injected with the optimal protective HLSOD dose, was examined during 27 days after tumor transplantation by the following parameters: (i) the number, migration and phagocytic activity of peritoneal macrophages, (ii) the phagocytic activity of blood polymorphonuclear leukocytes (PMNs), (iii) the responsibility in vitro of spleen lymphocytes to T and B cell mitogens. It was established that intraperitoneal inoculation of HLSOD produced a protective effect on the development of tumors. Elongation of the latent time for tumor appearance and inhibition of the tumor growth were observed. The decreased percentage of mortality in early stage of tumor progression was established. Immunological studies on tumor-bearing hamsters (TBH) induced a tem porary immunorestoring effect on the suppressed phagocytic activities of peritoneal macrophages and blood PMNs during the first 14 days of tumor development. Moreover, HLSOD showed an expressed stimulating effect on proliferative activity in vitro of spleen B lymphocytes from healthy and TBH as well. The immunorestoring and protective effect of the enzyme was probably due to improve of the oxidant-antioxidant balance in peritoneal phagocytes. The tem porary character of the effect can be explained with the interference of immunosuppressing factors produced by tumor tissue as well as by the presence of tumor antigens, tumor cells and antigen-antibody complexes in the circulation.

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