scholarly journals Isolation of Circulating Tumor Cells from Multiple Epithelial Cancers with ApoStream® for Detecting (or Monitoring) the Expression of Folate Receptor Alpha

2016 ◽  
Vol 11 ◽  
pp. BMI.S35075 ◽  
Author(s):  
Daniel J. O'Shannessy ◽  
Darren W. Davis ◽  
Kenna Anderes ◽  
Elizabeth B. Somers

This study describes our efforts to further the field of noninvasive diagnostics, specifically in the area of liquid biopsies in oncology. We employed laser scanning cytometry using highly selective antibodies to interrogate circulating tumor cells (CTCs) that were isolated using ApoStream® technology to identify folate receptor alpha (FRα)–positive cells. We demonstrate that FRα+ CTCs can be isolated from patients with metastatic cancers, including NSCLC adenocarcinoma, breast cancer, and ovarian cancer, whereas squamous cell lung cancer and normal healthy controls were devoid of FRα+ CTCs. We believe that the developed methodology will have applications in both the diagnosis and the monitoring of FRα-expressing cancers. Folate receptor alpha (FRα) expression may have utility as a potential diagnostic and therapeutic target in solid tumors. As tissue samples are not always available for patient screening, this study evaluated a noninvasive assay in CTCs from blood samples to detect FRα expression. The presence of FRα+ CTCs enriched using ApoStream® and detected using laser capture cytometry was evaluated in blood samples from cancer patients [NSCLC adenocarcinoma ( n = 14), breast cancer ( n = 20), ovarian cancer ( n = 6), and squamous lung cancer patients ( n = 6)] and healthy subjects ( n = 20). The data demonstrated that FRα+ CTCs were detected in blood from NSCLC adenocarcinoma, breast, and ovarian cancer patients, whereas squamous cell lung cancer patients and normal healthy controls lacked FRα+ CTCs as previously known. We demonstrate that CTCs captured using ApoStream® can be used to detect FRα+ CTCs and may have clinical utility as a real-time liquid biopsy for assessing FRα levels in cancer patients.

2006 ◽  
Vol 24 (26) ◽  
pp. 4254-4261 ◽  
Author(s):  
Keith L. Knutson ◽  
Christopher J. Krco ◽  
Courtney L. Erskine ◽  
Karin Goodman ◽  
Linda E. Kelemen ◽  
...  

Purpose Studies have demonstrated that the generation of immunity to tumor antigens is associated with improved prognosis for many cancers. A candidate antigen is the folate receptor alpha (FRα), which is overexpressed in breast and ovarian cancers. Our goal in this study was to attain a better understanding of the extent of endogenous FRα immunity. Methods Using a CD4+ T cell epitope prediction algorithm, we predicted promiscuous epitopes of FRα, and tested for immunity in 30 breast (n = 17) or ovarian (n = 13) cancer patients and 18 healthy donors using enzyme-linked immunospot analysis. Results Fourteen peptides were predicted, seven each from the carboxy- and amino-terminus halves of the protein. More than 70% of patients demonstrated immunity to at least one FRα peptide. Patients responded to an average of 3 ± 0.5 peptides, whereas healthy donors responded to 1 ± 0.4 peptides (P = .004). Five peptides were recognized by more than 25% of patients. Responses to three peptides were higher (P < .05) in patients than in healthy donors, suggesting augmented immunity. Compared with healthy individuals, patients developed higher immunity to the amino-terminus half of the receptor (P = .03). There was no difference between each group in the responses to nonspecific (P = .2) and viral stimuli (P = .5). Lastly, patients demonstrated elevated levels of FRα antibodies consistent with a coordinated immune response. Conclusion These findings demonstrate that the FRα is a target of the immune system in breast and ovarian cancer patients. Understanding which antigens are targeted by the immune system may be important for prognosis or immune-based therapies.


PLoS ONE ◽  
2009 ◽  
Vol 4 (7) ◽  
pp. e6292 ◽  
Author(s):  
Eati Basal ◽  
Guiti Z. Eghbali-Fatourechi ◽  
Kimberly R. Kalli ◽  
Lynn C. Hartmann ◽  
Karin M. Goodman ◽  
...  

Oncotarget ◽  
2016 ◽  
Vol 7 (14) ◽  
pp. 17442-17454 ◽  
Author(s):  
Leonora S.F. Boogerd ◽  
Martin C. Boonstra ◽  
Ann-Jean Beck ◽  
Ayoub Charehbili ◽  
Charlotte E.S. Hoogstins ◽  
...  

2018 ◽  
Vol 24 (13) ◽  
pp. 3014-3025 ◽  
Author(s):  
Kimberly R. Kalli ◽  
Matthew S. Block ◽  
Pashtoon M. Kasi ◽  
Courtney L. Erskine ◽  
Timothy J. Hobday ◽  
...  

Author(s):  
Muhannad Shweash ◽  
Saddam Jumaa Naseer ◽  
Maisam Khider Al-anii ◽  
Thulfiqar Fawwaz Mutar

Objective: Cancer ovary is one of the fatal gynecologic malignancies worldwide. Since breast cancer (BRCA) genes are considered tumor suppressor genes and play important roles in cancer by repairing of chromosomal damage with the error repair of DNA breaks. Therefore, breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2) gene mutations strongly enhance the development of ovarian cancer risk among women. Here, we report that both genes are an essential mediator of progress ovarian cancer, to determine the influence of BRCA1 and BRCA2 mutations in the improvement of ovarian cancer.Methods: A total of 25 subjects were chosen for the genetic studies, and three groups were recruited: fifteen ovarian cancer patients group, five healthy controls, and five first-degree relatives to a known case of ovarian cancer patients.Results: A genetic analysis revealed that a strong correlation exists between both gene mutations’ status in ovarian cancer, and BRCA gene mutations (185delAG, 5382insC, and 4153delA in BRCA1 and 6174delT in BRCA2) remained to establish to have a relatively high frequency among people in this study among ovarian cancer patients. Furthermore, seven patients with ovarian cancer carried all of the four investigated mutations, and five had three mutations.Conclusion: Otherwise, BRCA gene frequency showed low prevalence among first-degree relatives, and to a lesser extent among healthy controls, with only a few had all of the mutations combined. These data demonstrate for the first time a molecular link between BRCA1 and BRCA2 mutations in ovarian cancer progression in Iraq.


2019 ◽  
Vol 10 (3) ◽  
pp. 1640-1645
Author(s):  
Saleen Salam Abdulhadi ◽  
Abbas Abdullah Mohammed‎

In the present study, sequencing approach has been adopted for exploring the ‎genetic alteration of sequences for the ubiquitin gene (UBC) in patients of breast and ‎lung cancer and comparing the results with a normal sequence that obtained from NCBI. ‎The aim of this study was to detect for genetic alterations of UBC gene in the breast and ‎lung cancer patients then compare with healthy control subjects, to investigate the ‎association between the mutations at the intron region of the UBC gene and cancer disease, ‎‎40 blood samples were examined from patients with breast and lung cancer aged ranged from (17-65) years, were collected at Al-Amal Hospital of cancer in Baghdad ‎province/Iraq, the period of collecting samples were from October/2018 to January/2019. ‎While twenty-two blood samples from healthy control subjects were collected at ages ‎ranged from(19-59). After DNA extraction, the PCR primer was designed to amplify the ‎region in the UBC gene (part of exon 1 and the whole intron). Here we report the polymorphism of the intron sequence of the UBC gene in Iraqi population as the results of sequencing the PCR amplified products showed three different transition mutation G→A, ‎C→T, T→C in patients with breast cancer were also appeared in healthy control subjects. While nine transition mutations appeared in lung cancer patients, at different locations ‎of the sequence were detected by BLAST tool. ‎


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