Isolation of Circulating Tumor Cells of Ovarian Cancer by Transferrin Immunolipid Magnetic Spheres and Its Preliminary Clinical Application

Nano LIFE ◽  
2019 ◽  
Vol 09 (01n02) ◽  
pp. 1940001 ◽  
Author(s):  
Li Zuo ◽  
Wei Niu ◽  
Anqi Li

Circulating tumor cells (CTCs) play an important role in cancer prognosis, treatment monitoring and metastasis diagnosis. However, due to the extremely low concentration of CTC in the peripheral blood, its isolation and enrichment are critical steps for early diagnosis. Herein, we used the transferrin modified lipid magnetic spheres for the isolation of ovarian cancer CTCs, and studied the relationship between the CTCs count and the clinical case parameters, prognosis of ovarian cancer. The result showed that no CTC was found in the peripheral blood of 30 patients with benign cysts, and 34 out of 46 patients with ovarian cancer were positive for CTC, with a positive rate of 73.9%. Analysis of the parameters of the clinical cases showed that the positive rate of CTC was related to the clinical stages, and that it was not significantly related to the age, histopathological types and pathological grades of patients. Of the 34 CTC-positive patients, 18 had progression-free survival, with a survival rate of 52.9%, and of the 11 CTC-negative patients, 9 had progression-free survival, with a survival rate of 81.8%. The results showed that the transferrin lipid magnetic spheres prepared in this study, could effectively isolate the CTCs in the peripheral blood of patients with ovarian cancer, that the level of CTC in ovarian cancer patients was related to its clinical stage, and that the progression-free survival of the patients with a high level of CTCs was relatively short. Therefore, this study shows that the transferrin lipid magnetic sphere can achieve effective isolation of ovarian cancer CTC, which can be used as an auxiliary diagnostic method in comprehensive diagnosis of ovarian cancer.

Life ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 815
Author(s):  
Snezhanna O. Gening ◽  
Tatyana V. Abakumova ◽  
Dina U. Gafurbaeva ◽  
Albert A. Rizvanov ◽  
Inna I. Antoneeva ◽  
...  

Stem properties allow circulating tumor cells (CTCs) to survive in the bloodstream and initiate cancer progression. We aimed to assess the numbers of stem-like CTCs in patients with ovarian cancer (OC) before treatment and during first-line chemotherapy (CT). Flow cytometry was performed (Cytoflex S (Beckman Coulter, CA, USA)) using antibodies against CD45; epithelial markers EpCAM and cytokeratin (CK) 8,18; mesenchymal vimentin (vim); and stem-like CD44, CD133 and ALDH. This study included 38 stage I–IV OC patients (median age 66 (Q1–Q3 53–70)). The CK+vim- counts were higher (p = 0.012) and the CD133+ALDHhigh counts were lower (p = 0.010) before treatment in the neoadjuvant CT group than in the adjuvant group. The patients with ascites had more CK+vim- cells before treatment (p = 0.009) and less EpCAM-vim+ cells during treatment (p = 0.018) than the patients without ascites. All the CTC counts did not differ significantly in paired samples. Correlations were found between the CK-vim+ and CD133+ALDHhigh (r = 0.505, p = 0.027) and EpCAM-vim+ and ALDHhigh (r = 0.597, p = 0.004) cells before but not during treatment. Multivariate Cox regression analysis showed that progression-free survival was longer with the presence of surgical treatment (HR 0.06 95% CI 0.01–0.48, p = 0.009) and fewer CD133+ALDHveryhigh cells (HR 1.06 95% CI 1.02–1.12, p = 0.010). Thus, CD133+ALDH+ CTCs have the greatest prognostic potential in OC among the phenotypes studied.


2011 ◽  
Vol 122 (3) ◽  
pp. 567-572 ◽  
Author(s):  
Andres Poveda ◽  
Stanley B. Kaye ◽  
Robert McCormack ◽  
Songbai Wang ◽  
Trilok Parekh ◽  
...  

Author(s):  
Dalvinder Mandair ◽  
Mohid S Khan ◽  
Andre Lopes ◽  
Luke Furtado O’Mahony ◽  
Leah Ensell ◽  
...  

Abstract Background Circulating tumor cells (CTCs) are detectable in patients with neuroendocrine tumors (NETs) and are accurate prognostic markers although the optimum threshold has not been defined. Objective This work aims to define optimal prognostic CTC thresholds in PanNET and midgut NETs. Patients and Methods CellSearch was used to enumerate CTCs in 199 patients with metastatic pancreatic (PanNET) (90) or midgut NETs (109). Patients were followed for progression-free survival (PFS) and overall survival (OS) for a minimum of 3 years or until death. Results The area under the receiver operating characteristic curve (AUROC) for progression at 12 months in PanNETs and midgut NETs identified the optimal CTC threshold as 1 or greater and 2 or greater, respectively. In multivariate logistic regression analysis, these thresholds were predictive for 12-month progression with an odds ratio (OR) of 6.69 (P < .01) for PanNETs and 5.88 (P < .003) for midgut NETs. The same thresholds were found to be optimal for predicting death at 36 months, with an OR of 2.87 (P < .03) and 5.09 (P < .005) for PanNETs and midgut NETs, respectively. In multivariate Cox hazard regression analysis for PFS in PanNETs, 1 or greater CTC had a hazard ratio (HR) of 2.6 (P < .01), whereas 2 or greater CTCs had an HR of 2.25 (P < .01) in midgut NETs. In multivariate analysis OS in PanNETs, 1 or greater CTCs had an HR of 3.16 (P < .01) and in midgut NETs, 2 or greater CTCs had an HR of 1.73 (P < .06). Conclusions The optimal CTC threshold to predict PFS and OS in metastatic PanNETs and midgut NETs is 1 and 2, respectively. These thresholds can be used to stratify patients in clinical practice and clinical trials.


2020 ◽  
Vol 28 (4) ◽  
pp. 365-379
Author(s):  
Ana-Maria Muşină ◽  
Ionuţ Huţanu ◽  
Mihaela Zlei ◽  
Mădălina Ştefan ◽  
Mihaela Mentel ◽  
...  

AbstractIntroduction: Colorectal cancer (CRC) is the third most common neoplasia in the world. Circulating tumor cells (CTC) have a prognostic value and can be useful in monitoring solid neoplasia. Only one method for CTC identification has received the approval and this is the CellSearch® system based on the immunomagnetic separation. Multiple markers are used in CTC identification, as epithelial markers and cytokeratines. CTC identification in peripheral blood is associated with a worse prognostic and reduced free survival in CRC.Material and methods: We performed a systematic search in PubMed database for articles that reports the circulating tumor cells in CRC until July 2019. We selected studies in English and French and the main words used for search were ‘circulating tumor cells’, ‘colorectal cancer’, ‘colon cancer’, ‘rectal cancer’, ‘flow cytometry’, ‘peripheral blood’. We included studies with more than 10 patients, where samples were collected from the blood in relation with surgery and flow cytometry was used as analyzing technique.Results: We included 7 studies in final analysis, that showed in flow cytometry analysis a cut-off value of CTC that can vary from 2-4 CTC/ 7.5 ml peripheral blood with a sensitivity of 50.8% and specificity of 95%. Patients with positive CTC were associated with higher T stage and positive lymph nodes, with a worse overall survival (OS) and disease free survival (DFS) comparing with negative patients.Conclusion: CTC are considered to be a prognostic factor who needs more validation studies in order to be included in the clinical practice.


Cancers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 540 ◽  
Author(s):  
Pei-Hung Chang ◽  
Min-Hsien Wu ◽  
Sen-Yu Liu ◽  
Hung-Ming Wang ◽  
Wen-Kuan Huang ◽  
...  

Circulating tumor cells (CTCs) and immune status are strongly related to cancer prognosis, although few studies have examined both factors. This prospective observational study (ClinicalTrials.gov: NCT02420600) evaluated whether CTCs, circulating cancer stem-like cells (cCSCs), and peripheral lymphocytes with/without Programmed cell death protein 1 (PD-1) expression were associated with prognosis among patients receiving palliative chemotherapy for initially unresectable, recurrent/metastatic head and neck squamous cell carcinoma (rmHNSCC). Thirty-four patients were enrolled between January 2015 and June 2016. Overall survival (OS) was associated with a higher CTC number (hazard ratio [HR]: 1.01, p = 0.0004) and cCSC ratio (HR: 29.903, p < 0.0001). Progression-free survival (PFS) was also associated with CTC number (HR: 1.013, p = 0.002) and cCSC ratio (HR: 10.92, p = 0.003). A CD8+ proportion of ≥ 17% was associated with improved OS (HR: 0.242, p = 0.004). A CD4: CD8 ratio of >1.2 was associated with poorer trend of PFS (HR: 2.12, p = 0.064). PD-1 expression was not associated with survival outcomes. Baseline CTCs, cCSC ratio, and CD8+ ratio may predict prognosis in rmHNSCC.


Author(s):  
José Luiz GASPARINI-JUNIOR ◽  
Marcello Ferretti FANELLI ◽  
Emne Ali ABDALLAH ◽  
Ludmilla Thomé Domingos CHINEN

ABSTRACT Background: Metastasis is common in the diagnosis of pancreatic cancer, and the presence of epithelial-mesenchymal transition markers in circulating tumor cells may suggest worse prognosis. Aim: To correlate the number of circulating tumor cells (CTCs) in the peripheral blood of patients with a locally advanced or metastatic pancreatic tumor and the protein expression involved in epithelial-mesenchymal transition (EMT) in CTCs with clinical characteristics, progression-free survival (PFS) and overall survival (OS). Method: This was a prospective study conducted using peripheral blood samples collected at three different times. CTCs were quantified by the ISET test and analyzed by immunocytochemistry. Proteins involved in EMT (vimentin, TGFß-RI and MMP2) were analyzed in all CTCs. Results: Twenty-one patients were included. Median CTCs detected were 22, 20 and 8 CTCs/8 ml blood at baseline, first and second follow-up, respectively. No statistically significant correlation was found in correlating the number of CTCs and the evaluated clinical characteristics, PFS, or OS. There was no difference in PFS and OS among the EMT markers in the groups with and without markers. Conclusion: CTC analysis was not relevant in this sample for comparing clinical findings, PFS and OS in patients with pancreatic cancer. However, marker analysis in CTCs could be useful for the MMP-2 and/or TGFß-RI expression, as observed by the separate PFS curve.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 16068-16068
Author(s):  
S. Takeuchi ◽  
H. Tsubamoto ◽  
S. Adachi ◽  
K. Ito ◽  
Y. Itani ◽  
...  

16068 Background: For optimal debulked mullerian cancer (MC), the Intraperitoneal (IP) therapy has become the effective modality of chemotherapy to obtain better prognosis. We have reported KCOG9811study: IP CDDP + Paclitaxel (PTX) intravenous (IV) 2 cycles followed by 3 cycles of usual PTX-Carboplatin (abstr.1970, ASCO2002). And we have also reported the feasibility study and satisfactory response rate of the weekly IP-PTX with IV Carboplatin therapy (IP-PIVC, abstr. 5120, ASCO2005). Objectives: We have conducted two types of IP therapy for optimal debulked MC to improve the progression free survival (PFS) and overall survival (OS). Here are the prognosis and recurrent fashion after these IP therapies. Methods: Twenty patients (pts) with optimal debulked ovarian cancer were enrolled for KCOG9811, and eleven pts with optimal debulked MC newly/recurrent diagnosed disease were enrolled for IP-PIVC. The regimen of each therapy consisted of as follows: KCOG9811:50mg/ m2 of CDDP was administered via IP port at operation, after 2 weeks (wks) of operation, PTX was administered at a dose of 175mg/ m2IV for 3hrs on day 1, CDDP was administered at 75mg/ m2IP on day 2, every 3wks for 2 cycles, followed by PTX 175mg/ m2 IV and Carboplatin AUC5 IV on day1 every 3wks for 3 cycles. The IP-PIVC therapy consisted of IP-PTX, on days 1, 8, 15 at a dose of 45 mg/m2 (3pts) and 60 mg/m2(8pts). Carboplatin was administered monthly at a dose of AUC 5 on day 1 only. 2–6 cycles were performed. Results: The mean observation time was 72.6 months (m) and 32.6m for KCOG9811 and IP-PIVC, respectively. As for the median PFS was 1308+ days and 678+ days, and the median OS was 2180+ days and 978+ days, respectively. The five years survival rate showed 59.3% on KCOG9811, and the three years survival rate showed 75.8% on IP-PIVC. As for recurrent fashion, liver metastases and proximal lymphnodes metastases, and retroperitoneal metastases were detected. Few cases recurred Intraperitoneal lesion with small ascites Conclusions: There are some differences in the recurrent fashion of IP treatment from that of IV treatment. IP treatment prevented ascitic recurrence. Further improvement of chemotherapy is necessary for liver metastasis and proximal lymphnodes. [Table: see text]


Sign in / Sign up

Export Citation Format

Share Document