A novel method for monitoring response to chemotherapy based on the detection of circulating cancer cells: a case report.
We describe a novel method for detecting micrometastasis in the blood stream of cancer patients based on RT-PCR amplification of tumor-associated carcinoembryonic antigen (CEA) mRNA. To increase sensitivity and specificity of RT-PCR, CEA transcript was selectively up-regulated in cancer cells by exposure of peripheral blood to non-toxic concentrations of staurosporine (ST). Thereafter, polyA(+) RNA was extracted from tumor cells captured by means of magnetic beads coated with a monoclonal antibody against a common human epithelial antigen. Finally, RNA was subjected to RT-PCR analysis of CEA transcript. Using this approach, we demonstrated an ST-mediated increase in CEA transcript in blood specimens collected from a patient with metastatic colon cancer before receiving treatment with 5-fluorouracil/leucovorin. After a few cycles of chemotherapy, CEA-positive tumor cells were no longer detected. Clinical follow-up of this patient indicated that treatment with chemotherapy induced a dramatic reduction in liver metastasis. Therefore, it can be hypothesized that lack of CEA transcript detection might be consistent with disappearance or at least marked reduction of circulating tumor cells.
Aquino
A
A
Department of Neuroscience, University of Rome Tor Vergata, Italy. angelo.aquino@uniroma2.it
Prete
S P
SP
Balduzzi
A
A
Fossile
E
E
Formica
V
V
Torino
F
F
Bonmassar
L
L
Di Giacomo
A
A
Cappelletti
D
D
Cardillo
A
A
Graziani
G
G
D000230:Adenocarcinoma / Q000097:blood / Q000188:drug therapy* / Q000556:secondary; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002272:Carcinoembryonic Antigen / Q000235:genetics* / Q000378:metabolism; D003110:Colonic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D018189:Immunomagnetic Separation; D002955:Leucovorin / Q000008:administration & dosage; D008113:Liver Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000556:secondary; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis*; D012334:RNA, Neoplasm / Q000097:blood; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012680:Sensitivity and Specificity
D002272:Carcinoembryonic Antigen; D017931:DNA Primers; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D002955:Leucovorin; D005472:Fluorouracil