Detection of cancer cells in the peripheral blood of gastric cancer patients

Ikeguchi, Masahide; Ohro, Shotaro; Maeda, Yuichi; Fukuda, Kenji; Yamaguchi, Kensei; Shirai, Hajime; Kondo, Akira; Tsujitani, Shunichi; Kaibara, Nobuaki

doi:10.3892/ijmm.11.2.217

Cited by 19 publications

(32 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Among the 4 mRNA markers analyzed, CEA and MUC1 mRNA are suggested to play a more important role in GC staging, monitoring and prognosis than do hTERT and CK-19 mRNA. CEA mRNA has been proposed to be a more reliable marker than transcripts of cytokeratins for the detection of CTCs in peripheral blood of GC patients, 33 which is also in agreement with our findings.…”

Section: Discussionsupporting

confidence: 82%

“…To date, several tumor-associated mRNA markers have been demonstrated to be absent in normal cells but overexpressed in GC cells, for example, human telomerase reverse transcriptase (hTERT), cytrokeratin-19 (CK-19), carcinoembryonic antigen (CEA) and mucin 1 (MUC1). [12][13][14][15][16] These mRNA markers have been extensively tested for their application to the detection of circulating tumor cells (CTCs) in GC patients.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Development of a high‐throughput membrane‐array method for molecular diagnosis of circulating tumor cells in patients with gastric cancers

Lin

et al. 2006

Intl Journal of Cancer

View full text Add to dashboard Cite

Recently several noninvasive methods have been employed to detect circulating tumor cells (CTCs) in cancer patients. In this study, we have developed a highly sensitive, high-throughput colorimetric membrane-array method that was designed to detect a panel of mRNA markers including human telomerase reverse transcriptase (hTERT), , carcinoembryonic antigen (CEA) and mucin 1 (MUC1) mRNA for the presence of CTCs in the peripheral blood of patients with gastric cancer (GC). Digoxigenin-labeled cDNA targets synthesized following total RNA isolation from peripheral blood samples of 64 GC patients and 80 healthy individuals were subjected to membrane-array hybridization. The results showed that membrane array could positively detect 5 cancer cells/ml of peripheral blood in GC cell-dilution experiments. The sensitivity, specificity and diagnostic accuracy for hTERT, CK-19, CEA and MUC1 mRNA ranged from 78.1% to 82.8%, 76.3% to 85% and 81.3% to 83.3%, respectively. Both CEA and MUC1 mRNA expression was correlated significantly with all malignant biological properties of GC, such as macroscopic type, depth of tumor invasion, lymph-node metastasis, TNM stage and coexisting distant metastasis (all p < 0.05). Using these 4 markers in combination, the sensitivity, specificity and diagnostic accuracy of membrane array were raised to 89.1%, 91.3% and 90.3%, respectively. The expression of all 4 mRNA markers was an independent predictor for postoperative recurrence/metastasis. GC patients with the expression of all the 4 mRNA markers showed a poorer survival rate than those without the expression of any 1 mRNA marker (p 5 0.0223). These findings demonstrated that our membrane-array method could detect CTCs in the circulation of GC patients with considerably high sensitivity and specificity. The identification of CTCs in the peripheral blood may be useful in the auxiliary cancer diagnostics or postoperative surveillance of GC patients for recurrence/metastasis. ' 2006 Wiley-Liss, Inc.Key words: circulating tumor cell; membrane array; gastric cancer; molecular diagnosisThe degrees of tumor penetration in the stomach wall and lymph node metastasis have been used for many decades as the 2 major prognostic determinants for gastric cancer (GC) patients. Unfortunately, despite informative staging of patients with GC, some patients with apparently localized disease at diagnosis will subsequently develop recurrent or metastatic diseases. 1-4 One of the major causes is attributed to the presence of disseminated tumor cells shed from the primary carcinoma into circulation, prior to or during surgery. Even in patients with early GC, blood-born metastasis occurs. 2,5,6 Recent attempts to improve staging include sensitive detection of disseminated tumor cells in the blood or lymph nodes by molecular approaches. Evidence increasingly clarifies that primary cancers begin shedding neoplastic cells into the circulation at an early stage. [7][8][9] It is the dissemination of cancer cells into circulation that is widely accepted as the main cause l...

show abstract

Section: Discussionsupporting

confidence: 82%

mentioning

confidence: 99%

Development of a high‐throughput membrane‐array method for molecular diagnosis of circulating tumor cells in patients with gastric cancers

Lin

et al. 2006

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…TBP was chosen because there are no known retropseudogenes [6], and the gene expression level of TBP is lower than that of the target genes. The cDNAs were prepared from 1.5 ml of peripheral blood (PB) samples obtained from 8 healthy volunteers [7]. The ∆Ct values for IL-2 and -12 in the PB samples were determined by subtracting the IL-2 and -12 Ct values from the TBP Ct value.…”

Section: Quantitative Real-time Rt-pcr Assaymentioning

confidence: 99%

Interleukin-2 Gene Expression Is a New Biological Prognostic Marker in Hepatocellular Carcinomas

Ikeguchi¹,

Hirooka²

2005

Oncol Res Treat

Self Cite

View full text Add to dashboard Cite

Background: Cytokines produced by tumor cells and tumor-infiltrating lymphocytes (TIL) appear to regulate tumor cell growth. The present study analyzed the correlation between local immune responses and cytokine gene expression levels in patients with primary hepatocellular carcinoma (HCC). Material and Methods: The gene expression levels of interleukin-2 (IL-2) and -12 (IL-12) were evaluated quantitatively by real-time reverse transcriptase polymerase chain reaction (RT-PCR) and compared with the density of CD8+ TIL detected by immunohistochemistry in 59 surgically resected HCCs. Results: IL-2 gene expression was detected in 33 (56%) and IL-12 gene expression in 39 (66%) of 59 HCCs. Tissueinfiltrating CD8+ T lymphocytes in tumors were significantly suppressed compared with noncancerous liver tissues. The CD8+ T cell density of tumors with IL-2 gene expression was higher than that of tumors without IL-2 gene expression (p = 0.002). However, such a correlation was not detected in tumors with or without expression of IL-12 genes. Patients with IL-2 positive tumors had a favorable prognosis. IL-2 gene expression was detected as an important prognostic factor independent of tumor stage. Conclusions: These findings indicate that in HCCs, tumor-infiltrating CD8+ T cells might be activated by IL-2 produced by TIL and IL-2 gene expression in tumors may be an important prognostic biomarker in HCC.

show abstract

“…TBP was chosen because there are no known retropseudogenes [8] , and the level of TBP gene expression is lower than that of c -myc . The cDNAs were prepared from 1.5 ml of peripheral blood (PB) samples from 8 healthy volunteers [9,10] . The ¢ Ct value for c -myc in the PB samples was determined as follows: ¢ Ct c -myc = TBP Ct value -c -myc Ct value.…”

Section: Quantitative Real-time Reverse Transcriptase Polymerase Chaimentioning

confidence: 99%

Expression of c<i>-myc</i> mRNA in Hepatocellular Carcinomas, Noncancerous Livers, and Normal Livers

Ikeguchi

Hirooka²

2004

Pathobiology

Self Cite

View full text Add to dashboard Cite

Objectives: c-myc is a transcription factor that regulates cell proliferation, differentiation, and apoptosis. However, little is known about the clinical importance of c-myc mRNA expression in a primary hepatocellular carcinoma (HCC). In this study, we investigated whether a correlation existed between the level of c-myc mRNA expression and the occurrence of apoptosis or proliferative activity in an HCC. Methods: The levels of c-myc mRNA expression were quantified by real-time reverse transcriptase polymerase chain reaction (RT-PCR) and compared with immunohistochemical detection of the occurrence of spontaneous apoptosis and proliferative activity of cancer cells in 59 surgically resected HCCs. Results: The mean level of c-myc mRNA expression in 59 HCCs (1.19) was significantly suppressed compared with that in 59 noncancerous liver tissues (1.44, p < 0.0001). The level of c-myc mRNA expression was not correlated with tumor differentiation, tumor progression, proliferative activity of cancer cells, or patient survival. However, there was a significant positive correlation between the levels of c-myc mRNA expression and the occurrence of apoptosis in 59 HCCs (p < 0.001). Conclusions: Inhibition of c-myc mRNA expression may obstruct the induction of apoptosis of HCC cells and lead to uncontrolled cell growth.

show abstract

Detection of cancer cells in the peripheral blood of gastric cancer patients

Cited by 19 publications

References 0 publications

Development of a high‐throughput membrane‐array method for molecular diagnosis of circulating tumor cells in patients with gastric cancers

Development of a high‐throughput membrane‐array method for molecular diagnosis of circulating tumor cells in patients with gastric cancers

Interleukin-2 Gene Expression Is a New Biological Prognostic Marker in Hepatocellular Carcinomas

Expression of c<i>-myc</i> mRNA in Hepatocellular Carcinomas, Noncancerous Livers, and Normal Livers

Contact Info

Product

Resources

About