Sensitive Assay for Detection of Hepatocellular Carcinoma Associated Gene Transcription (α-Fetoprotein mRNA) in Blood

Matsumura, Masaru; Niwa, Yuki; Hikiba, Yohko; Okano, Kenichi; Kato, Natsumi; Shiina, S.; Shiratori, Yoshimune; Omata, Masao

doi:10.1006/bbrc.1995.1259

Cited by 41 publications

(31 citation statements)

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“…Tissue-specific antigens (such as albumin, AFP, tyrosinase, prostate-specific antigen and tyrosine hydroxylase), the neuroendocrine protein, keratin 19, and the metastaticassociated antigen CD44 have been used as marker genes to detect tumour micrometastasis in the blood, bone marrow or lymph nodes (Naito et al, 1991;Smith et al, 1991;Matsumura and Tarin, 1992;Mattano et al, 1992;Moreno et al 1992;Deguchi et al, 1993;Hillaire et al, 1994;Israeli et al, 1994;Matsumura et al, 1994Matsumura et al, , 1995Schoenfeld et al, 1994;Kar and Carr, 1995;Komeda et al, 1995). The detection sensitivities ranged from one tumour cell per 105 to 107 normal cells (Johnsum et al, 1995).…”

Section: Resultsmentioning

confidence: 99%

“…Patients may have 105 or more tumour cells in their circulation when AFP mRNA was detected by the nested PCR. Comparison of the sensitivities of RT-PCR and nested PCR revealed that nested PCR provided 100-fold better sensitivity (Matsumura et al, 1995). Furthermore, nested PCR has increased specificity owing to the use of two pairs of specific primers.…”

Section: Resultsmentioning

confidence: 99%

“…To understand stage tumour progression better, several laboratories have reported using the polymerase chain reaction (PCR) to detect metastatic cells in peripheral blood or lymph nodes (Johnsum et al, 1995). These studies made use of the detection of mRNA expression of tissuespecific antigens (Natio et al, 1991;Smith et al, 1991;Mattano et al, 1992; Moreno et al, 1992;Deguchi et al, 1993;Hillaire et al, 1994;Israeli et al, 1994;Matsumura et al, 1994Matsumura et al, , 1995Schoenfeld et al, 1994; Kar and Carr, 1995;Komeda et al, 1995) and the metastatic-associated antigen CD44 (Matsumura et al, 1992).…”

mentioning

confidence: 99%

“…For HCC, reverse transcription PCR (RT-PCR) has been used to detect albumin and AFP expression in the blood of HCC and hepatitis patients (Hillaire et al, 1994;Matsumura et al, 1994Matsumura et al, -1995Kar and Carr, 1995;Komeda et al, 1995). Positive albumin and AFP expression in the blood was found to be associated with early subsequent relapse (Hillaire et al, 1994;Komeda et al, 1995).…”

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confidence: 99%

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Detection of alphafetoprotein-expressing cells in the blood of patients with hepatoma and hepatitis

Jiang

Shyu²,

Huang³

et al. 1997

Br J Cancer

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Summary The presence of tumour cells in the blood circulation may predict disease recurrence and metastasis. We have evaluated the specificity and sensitivity of detecting hepatoma cells in blood using nested polymerase chain reaction with primers specific for the alphafetoprotein (AFP) gene. The nested polymerase chain reaction amplified a 270-base pair AFP DNA fragment from cDNA of Hep 3B hepatoma cells. In a reconstitution experiment, AFP mRNA was detected from peripheral mononuclear cells isolated from 10 ml of blood containing as few as ten Hep 3B cells. Peripheral mononuclear cells from the blood of 20 hepatoma patients were analysed, and 19 patients showed positive AFP mRNA expression. Seven of 13 samples from hepatitis patients also showed positive AFP mRNA expression. All five paired samples of peripheral blood or umbilical cord blood from pregnant mothers and their babies, respectively, showed positive AFP expression. None of 22 control samples was positive. The presence of AFP mRNA in the blood of hepatitis or hepatoma patients suggests the presence of circulating hepatoma cells or hepatocytes in the circulation. The high incidence of AFP mRNA in the blood of hepatoma patients supports the notion of early haematogenous spreading of the disease.Keywords: alphafetoprotein; hepatocellular carcinoma; hepatitis; polymerase chain reaction Hepatocellular carcinoma (HCC) is one of the most common malignancies in Taiwan, mainland China and southern Africa. The disease is highly associated with hepatitis B and C virus infections as well as with the carcinogen aflatoxin (Chen, 1987). Despite improved survival of some cancer patients in recent years, the therapeutic efficacy for HCC remains very limited. Survival after the onset of symptoms is only a few months (Lai et al, 1987). It is therefore important to establish techniques for the early diagnosis of HCC.Alphafetoprotein (AFP) is a glycoprotein that is normally expressed during embryogenesis. The concentration of AFP in serum decreases as the liver develops and matures. However, AFP levels can become elevated in some disease states, particularly in HCC (Bellet et al, 1985;Chen, 1987;Di Bisceglie and Hoofnagle, 1989). Elevated serum AFP is employed as a highly specific and sensitive marker for the diagnosis of HCC, as about 82% of HCC patients have elevated serum AFP levels (Bellet et al, 1985). However, AFP can also be elevated in non-malignant forms of liver disease, such as acute and chronic hepatitis and cirrhosis (Chen, 1987;Di Bisceglie and Hoofnagle, 1989). In addition, increasing AFP levels have also have been associated with liver regeneration (Silver et al, 1974).A major characteristic of cancer is the ability of tumour cells to metastasize to other sites. The process of tumour metastasis involves multiple host-tumour interactions, and it is thought that (Chen, 1987). To understand stage tumour progression better, several laboratories have reported using the polymerase chain reaction (PCR) to detect metastatic cells in peripheral blood or lymph nod...

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Detection of alphafetoprotein-expressing cells in the blood of patients with hepatoma and hepatitis

Jiang

Shyu²,

Huang³

et al. 1997

Br J Cancer

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“…For detection of circulating tumor cells, RT-PCR has been utilized [22][23][24], and we found CK-8 expression have been demonstrated to be positive in blood. Through the travel in the circulation, only a small percentage of tumor cells (<0.01%) released from a primary tumor survive and arrest in the capillary beds of distant organs producing a successful metastasis [25].…”

Section: Establishment Of An In Vivo Highly Metastatic Rat Hcc Modelmentioning

confidence: 92%

Animal Model of Lung Metastasis of Hepatocellular Carcinoma: A Tool for the Development of Anti-Metastatic Therapeutics

Futakuchi¹

2013

JCT

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We observed that N-nitrosomorpholine (NMOR) given after a multi-carcinogenic treatment induced liver carcinomas with 56% lung metastasis. An additional treatment with diethylnitrosamine (DEN) with NMOR further enhanced the incidence of hepatocellular carcinoma (HCC) with lung metastasis. We have further revised the duration of NMOR treatment to establish an animal model with a simple experimental protocol and an appropriate experimental duration to facilitate investigation exploring the mechanisms of HCC metastasis and development of anti-metastatic therapeutics. We observed that DEN exposure followed by a 16-week treatment with NMOR to be a most efficient protocol for the induction of HCC metastasizing to the lung. In this review, we will discuss about the usefulness of animal models for induction of highly metastatic HCC and the assessment of the efficacy of anti-metastatic therapeutics. Additionally, we will also discuss use of these models in analysis of individual steps in the metastatic process by using non-steroidal anti-inflammatory drugs, aspirin and indomethacin, two nuclear factor kappa B (NF-κB) inhibitors, pentoxifylline and N-acetyl-L-cysteine.

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Circulating Messenger RNA of α-Fetoprotein

Jeng

Sheen²,

Tsai³

2004

Arch Surg

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Hypothesis: Isolated tumor cells may be associated with micrometastasis. Circulating ␣-fetoprotein messenger RNA (AFP mRNA) in patients with hepatocellular carcinoma (HCC) has been considered to represent isolated tumor cells. We propose that circulating AFP mRNA may have prognostic value after curative resection of HCC. Design: A prospective cohort study. Setting: Referral center. Patients: Eighty-one consecutive patients who underwent curative resection of HCC. Measurements: A nested reverse-transcriptase polymerase chain reaction (RT-PCR) assay for circulating AFP mRNA before and again 12 weeks after surgery in 81 patients and in a control group. Clinicopathological variables and postoperative course (recurrence and recurrence-free survival) were examined for correlation with the levels of circulating AFP mRNA. Results: Of the 81 patients, 22 (27.2%) and 19 (23.4%) had AFP mRNA detected preoperatively and postoperatively, respectively. The recurrence-free survival at 1, 2, and 3 years after resection was significantly shorter in the latter patients (52.6%, 15.6%, and 0%, respectively; P Ͻ.001) but not in the former (81.8%, 54.5%, and 29.2%; P =.28). In univariate analysis, a significantly higher recurrence rate was found in patients with liver cirrhosis (P=.03), Edmondson-Steiner differentiation grade III or IV (P Ͻ.001), incomplete or absent capsule (P=.001), vascular invasion (P Ͻ.001), daughter nodules (P=.003), or a positivity for postoperative circulating AFP mRNA (P Ͻ.001). Postoperative positivity for circulating AFP mRNA remained a significant risk factor (P=.002; hazard ratio 3.13; 95% confidence interval, 1.52-6.47) in the multivariate analysis. Conclusion: The detection of circulating AFP mRNA 12 weeks postoperatively is associated with an increased and earlier risk of HCC recurrence.

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Sensitive Assay for Detection of Hepatocellular Carcinoma Associated Gene Transcription (α-Fetoprotein mRNA) in Blood

Cited by 41 publications

References 0 publications

Detection of alphafetoprotein-expressing cells in the blood of patients with hepatoma and hepatitis

Detection of alphafetoprotein-expressing cells in the blood of patients with hepatoma and hepatitis

Animal Model of Lung Metastasis of Hepatocellular Carcinoma: A Tool for the Development of Anti-Metastatic Therapeutics

Circulating Messenger RNA of α-Fetoprotein

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