close

Вход

Забыли?

вход по аккаунту

?

Clonal karyotypic abnormalities of the hereditary multiple exostoses chromosomal loci 8q24.1 (EXT1) and 11p11-12 (EXT2) in patients with sporadic and hereditary osteochondromas

код для вставкиСкачать
1643
The Usefulness of Determining
Des-g-Carboxy Prothrombin by Sensitive
Enzyme Immunoassay in the Early Diagnosis
of Patients with Hepatocellular Carcinoma
Yuhsaku Mita, M.D.
Yutaka Aoyagi, M.D.
Masahiko Yanagi, M.D.
Takeshi Suda, M.D.
Yasufumi Suzuki, M.D.
Hitoshi Asakura, M.D.
BACKGROUND. Measurements of serum concentrations of des-g-carboxy pro-
Third Division, Department of Internal Medicine,
Niigata University School of Medicine, Niigata,
Japan.
Supported in part by a Grant-in-Aid (05670457)
for Scientific Research from the Ministry of Education, Science and Culture of Japan and a
Grant-in-Aid from the Niigata University Science
Foundation.
The authors thank Miss Yumiko Shimizu for her
technical assistance.
Address for reprints: Yutaka Aoyagi, M.D., Third
Division, Department of Internal Medicine, Niigata University School of Medicine, 757 Asahimachi Dori-1-Bancho, Niigata 951, Japan.
Received June 27, 1997; revision received November 25, 1997; accepted November 25, 1997.
thrombin (DCP) are widely used for diagnosing hepatocellular carcinoma (HCC).
However, the DCP is not always sensitive enough to detect small HCCs. In the
current study, the authors investigated the usefulness of DCP in the early diagnosis
of HCC, using a more sensitive enzyme immunoassay than is conventionally employed.
METHODS. The authors examined 148 serum samples with DCP concentrations
from a conventional assay of less than 100 mAU (arbitrary unit)/mL from 91 patients with HCC and 57 with cirrhosis. DCP concentrations were determined by a
more sensitive enzyme immunoassay (ED-036 kit, Eisai Laboratory, Tokyo, Japan)
with a minimal detection level of 10 mAU/mL. Ninety-one HCC patients had 43
solitary small HCCs (with a greatest dimension of less than 2 cm). Of these 43
HCCs, 12 were well differentiated.
RESULTS. The mean serum concentration of DCP in HCC (48.3 { 24.3, mean {
standard deviation [SD]) was higher than in cirrhosis (20.3 { 10.3); this difference
was statistically significant. When the tentative cutoff level of 40 mAU/mL (almost
corresponding to the mean value / 2SD in patients with cirrhosis) was used as
the level of discriminating HCC from cirrhosis, 62% of patients (56 of 91) with
HCC had DCP values above this level (sensitivity). However, only three patients
with cirrhosis had higher DCP levels. Thus, the specificity of this test was 95% (54
of 57 patients). The total accuracy was 74% (56 / 54/91 / 57). Twenty-three of 43
solitary small HCCs (53%) had DCP values above the cutoff level. Furthermore, 7
of 12 (58%) small, well-differentiated HCCs less than 2 cm in greatest dimension
had higher DCP values.
CONCLUSIONS. The results of this study indicate that DCP determination by sensitive enzyme immunoassay is useful in the early diagnosis of HCC because a high
specificity is maintained. Cancer 1998;82:1643–8. q 1998 American Cancer Society.
KEYWORDS: des-g-carboxy prothrombin, a-fetoprotein, hepatocellular carcinoma,
early diagnosis, enzyme immunoassay.
E
arly diagnosis of hepatocellular carcinoma (HCC) is very important
during the follow-up of patients with chronic liver diseases because of the high incidence of HCC in association with cirrhosis.1 For
this purpose, measurements of des-g-carboxy prothrombin (DCP)
and a-fetoprotein (AFP) concentrations,2 – 8 along with several imaging
modalities, have been used widely.9 – 13 However, DCP has not always
been sensitive enough to detect small HCCs with a greatest dimension
of less than 2 cm. AFP sometimes turned positive in nonneoplastic
q 1998 American Cancer Society
/ 7bc2$$1045
04-09-98 16:12:43
cana
W: Cancer
1644
CANCER May 1, 1998 / Volume 82 / Number 9
TABLE 1
Clinical Features of Patients with HCC and Cirrhosis in the Current
Study
Features
HCC
Cirrhosis
Median age, yrs (range)
Male-to-female ratio
Positive for HBsAg
Positive for anti-HCV
Negative for both HBsAg
and anti-HCV
Positive for both HBsAg
and anti-HCV
Complication of cirrhosis
61 (42–80)
1.5
17% (15 of 91)
70% (64 of 91)
59 (33–78)
0.78
32% (18 of 57)
40% (23 of 57)
13%a (12 of 91)
28%b (16 of 57)
0% (0 of 91)
69% (63 of 91)
0% (0 of 57)
HCC: hepatocellular carcinoma; HCV: hepatitis C virus; HBsAg: hepatitis B virus surface antigen.
a
This HCC group includes 2 patients with autoimmune hepatitis and 2 with cirrhosis who had a history
of habitual alcohol intake of more than 120 g/day for more than 10 years.
b
This cirrhosis group includes 1 patient with autoimmune hepatitis, 1 with primary biliary cirrhosis,
and 7 with cirrhosis who had a history of habitual alcohol intake of more than 120 g/day for more
than 10 years.
liver diseases, although the sensitivity was higher than
that of DCP.14 – 16 Measurement of a lens culinaris agglutinin reactive species of AFP raised the specificity
of AFP in discriminating between HCC and nonneoplastic liver diseases.17 – 20 Fucosylation of the carbohydrate chain is the molecular basis for this species.21,22
Therefore, a more reliable and sensitive assay system
for DCP is desired.
In the current study, we investigated the usefulness of DCP in the early diagnosis of HCC by using
a more sensitive enzyme-immunoassay than is conventionally employed.
METHODS
Patients
Serum samples from 148 patients, 91 with HCC and
57 with cirrhosis, were used in the current study. (The
DCP concentrations were determined by the conventional immunoassay and were less than the cutoff level
of 100 mAU [arbitrary unit]/mL.) The clinical features
of these patients are summarized in Table 1. Patients
with well-differentiated HCC were diagnosed by fineneedle biopsy under the guidance of ultrasonography.
The remaining patients were diagnosed by biopsy, autopsy, and operation specimens, and clinically by ultrasonography, computed tomography, magnetic resonance imaging, and selective celiac angiography
combined with measurements of DCP and AFP with
a fucosylation index.
DCP Determination by Sensitive Enzyme Immunoassay
The serum DCP concentrations were determined by
sensitive enzyme immunoassay (ED-036 kit, Eisai Lab-
/ 7bc2$$1045
04-09-98 16:12:43
cana
oratory, Tokyo, Japan) according to the manufacturer’s instructions. The monoclonal antibody to DCP
and the basic composition of the reagents in the sensitive enzyme immunoassay ED-036 kit were essentially
similar to those in EI-test mono-P-II. Major alterations
were as follows: First, the standard DCP was obtained
by the chemical modification of purified prothrombin.
In the conventional enzyme immunoassay, it was purified from the patients’ sera, which was subjected to
warfarin treatment. Second, the standard DCP was diluted with normal human plasma in the conventional
assay. In the sensitive assay, it was diluted with a 7.5%
bovine serum albumin (BSA) solution. In both the conventional and the sensitive assay kits, peroxidaselabeled antiprothrombin antibody was used in the second-step incubation. This enzyme reaction was determined by the absorbance at 405 nm. Normal human
sera used for the dilution of standard DCP in the conventional kit demonstrated that the absorbance was
approximately 0.1 at 405 nm; and in the sensitive
assay, the absorbance of the 7.5 % BSA solution was
approximately 0.04. The difference in the absorbance
at 405 nm between normal human sera and BSA (approximately 0.06) corresponded to about 30 mAU/mL
of DCP. This exchange decreased the absorbance of
reference and contributed to improving the minimal
detection level of DCP in the sensitive assay. Third,
the first incubation time was prolonged for 16 hours
at 4 7C. With the conventional kit, the first incubation
was usually performed for 2 hours at room temperature. The conventional kit also alternatively recommended that the first incubation time be 16 hours at
4 7C overnight. These alterations made it possible to
improve the minimal detection level from 100 mAU/
mL to 10 mAU/mL. The reproducibility of the sensitive
assay was as follows: The intra-assay (within run precision) reproducibility was assessed by repeated analysis
of 3 samples in three consecutive assays, and the calculated coefficients of variation were 2.1%, 2.9%, and
4.1% (mean, 3.03%). The interassay (day-to-day precision) reproducibility was assessed by repeated analysis
of 3 samples in 5 assays, and the calculated coefficients
of variation were 2.3%, 5.1%, and 6.9% (mean,
4.77%).23,24
Fucosylation Index of AFP
The measurement of the fucosylation index of AFP was
performed by crossed immunoaffinoelectrophoresis
in the presence of lens culinaris agglutinin, as described previously.17
Conventional DCP and AFP Determinations
The serum concentrations of DCP and AFP were determined by respective conventional enzyme immunoas-
W: Cancer
Sensitive Determination of DCP in Early HCC/Mita et al.
1645
TABLE 2
Diagnostic Values for Detection of HCC by Improved Sensitive DCP
Assay
Overall accuracy
Sensitivity
Specificity
Positive predictive value
Negative predictive value
74% (56 / 54/91 / 57)a
62% (56/91)b
95% (54/57)c
95% (56/56 / 3)d
61% (54/35 / 54)e
HCC: hepatocellular carcinoma; DCP: des-g-carboxy prothrombin; TP: true-positive; TN: true-negative;
FP: false-positive; FN: false-negative.
a
Overall accuracy: TP / TN/TP / FP / TN / FN.
b
Sensitivity: TP/TP / FN.
c
Specificity: TN/FP / TN.
d
Positive predictive value: TP/TP / FP.
e
Negative predictive value: TN/FN / TN.
kits (Dainabott Co. Ltd., Tokyo, Japan, and Ortho Diagnostics, Raritan, NJ).
RESULTS
FIGURE 1. Serum concentrations of des-g-carboxy prothrombin (DCP)
from 91 patients with hepatocellular carcinoma (HCC) and 57 with cirrhosis
(LC) are shown. There is a statistically significant difference between the
serum concentrations of DCP in HCC (48.3 { 24.3, mean { standard
deviation) and those in cirrhosis (20.3 { 10.3), as determined by an
unpaired Student’s t test (P õ 0.001). Vertical lines indicate the mean {
standard deviation.
says (AFP was determined by enzyme-linked immunoadsorbent assay [ELISA]-AFP, International Reagents, Kobe, Japan, and DCP was determined with
the EI-test mono-P-II kit, Eisai Laboratory, Tokyo, Japan), according to the manufacturers’ instructions.
The cutoff levels of AFP and DCP were fixed at 20 ng/
mL and 100 mAU/mL, respectively.
Hepatitis B Surface Antigen and Anti–Hepatitis C Virus
Antibody Determinations
Serum hepatitis B surface antigen (HBsAg) and anti –
hepatitis C virus (HCV) antibody were determined by
enzyme immunoassay using commercially available
/ 7bc2$$1045
04-09-98 16:12:43
cana
Figure 1 shows the comparison of the distribution of
DCP in the serum of 91 patients with HCC and 57 with
cirrhosis. The mean value of serum concentrations of
DCP in HCC, which ranged between 10 and 112 mAU/
mL, was 48.3 { 24.3 (mean { standard deviation [SD]).
The value for cirrhosis, which ranged between 10 and
57 mAU/mL, was 20.3 { 10.3. There was a statistically
significant difference between the mean values of DCP
in HCC and cirrhosis (P õ 0.001). When the tentative
cutoff level of 40 mAU/mL, which almost corresponded to the mean value / 2SD for patients with
cirrhosis, was used as the level of discriminating HCC
from cirrhosis, 56 of 91 patients (62%) with HCC had
DCP values above this level (sensitivity). Only three
patients with cirrhosis, however, had DCP values
above this level. Thus, the specificity of this test for
cirrhosis was 95% (54 of 57), and total accuracy was
74% (56 / 54/91 / 57). These results are summarized
in Table 2.
Increased concentrations of AFP above 20 ng/mL
were observed in 43 of 91 patients with HCC (47%),
as shown in Table 3. The fucosylation index was determined for 30 of 43 patients with HCC, with increased
AFP concentrations of more than 30 ng/mL and a
mean fucosylation index of 17 { 27%. On the other
hand, increased concentrations of AFP were also observed in 8 of 57 patients with cirrhosis. No evidence
of HCC, however, was observed in these patients with
cirrhosis by several imaging modalities in the subsequent follow-up period, which continued for longer
than 6 months after sample collections. The mean fucosylation index for cirrhosis was 5 { 5%, and there
was a significant difference in the fucosylation index
W: Cancer
1646
CANCER May 1, 1998 / Volume 82 / Number 9
TABLE 3
Diagnostic Values by Improved Sensitive DCP Assay and AFP According to Categories of HCC
Categories of HCC (no. of patients)
Sensitivity of DCP
Sensitivity of AFP
Sensitivity of both
DCP and AFP
All HCCs (91)
Small, solitary HCCs less than 2 cm in
greatest dimension (43)
Well-differentiated HCCs (17)
Well-differentiated HCCs less than 2 cm
in greatest dimension (12)
62% (56/91)
47% (43/91)
84% (76/91)
53% (23/43)
71% (12/17)
49% (21/43)
29% (5/17)
84% (36/43)
82% (14/17)
58% (7/12)
25% (3/12)
75% (9/12)
HCC: hepatocellular carcinoma; DCP: des-g-carboxy prothrombin; AFP: a-fetoprotein.
between HCC and cirrhosis (P Å 0.025). The remaining
48 of 91 patients with HCC had AFP concentrations of
less than 21 ng/mL, and 33 of 48 patients with HCC
(69%) without increased AFP had elevated concentrations of DCP of more than 40 mAU/mL, as shown in
Table 4.
To obtain detailed information about the relation
between DCP concentrations and greatest tumor dimension of HCC, the next analysis was performed.
When graded according to the greatest tumor dimension, the HCC patient group included 43 small
solitary HCCs with a greatest dimension of less than
2 cm. These patient categories corresponded to the
‘‘small liver cancer’’ categories defined by the Liver
Cancer Study Group of Japan. Twenty-three of 43 patients with small HCCs (53%) had increased concentrations of DCP of more than 40 mAU/mL. On the
other hand, for 21 of 43 patients with small HCCs
(49%), elevated AFP concentrations were indicated, as
shown in Table 3. In the 22 patients with small HCCs
that did not produce AFP, 15 of 22 (68%) had increased
concentrations of DCP of more than 40 mAU/mL (Table 4).
In the next analysis, we graded the HCC patients
according to a combination of tumor size and histologic characteristics. The HCC group was comprised
of 17 cases of well-differentiated HCC, and in 12 of
these 17 cases the tumors were less than 2 cm in
greatest dimension. Seven of 12 patients with welldifferentiated HCCs (58%) whose tumors had a greatest dimension of less than 2 cm had elevated DCP
concentrations (Table 3). All 5 of the patients with
well-differentiated HCCs whose tumors had a greatest dimension of more than 2 cm had elevated DCP
concentrations, but only 2 of the 5 had elevated AFP
concentrations. To sum up, positive reactions were
noted in the following percentages of all the patients
with well-differentiated HCCs: with DCP, 71% (12 of
17); with AFP, 29% (5 of 17); and with the combination
of DCP and AFP, 82% (14 of 17). In patients with well-
/ 7bc2$$1045
04-09-98 16:12:43
cana
TABLE 4
Diagnostic Values by Improved Sensitive DCP Assay in 48 Patients
with HCC Whose AFP Concentrations Were Less than 21 ng/mL
Categories of HCC (no. of patients)
Sensitivity of DCP
All HCCs (48)
Small, solitary HCCs less than 2 cm in
greatest dimension (22)
Well-differentiated HCCs (12)
Well-differentiated HCCs less than 2 cm
in greatest dimension (9)
69% (33/48)
68% (15/22)
75% (9/12)
67% (6/9)
DCP: des-g-carboxy prothrombin; HCC: hepatocellular carcinoma; AFP: a-fetoprotein.
differentiated HCCs whose tumors had a greatest dimension of less than 2 cm, 58% (7 of 12) showed
positivity with DCP, 25% (3 of 12) with AFP, and 75%
(9 of 12) with the combination. The diagnostic values
of the current sensitive DCP assay and AFP determinations, according to categories of HCC, are summarized in Tables 3 and 4.
DISCUSSION
Two kinds of trials have been performed to increase
sensitivity with a conventional enzyme immunoassay
kit. The first trial, by Saitoh et al., introduced an avidinbiotin method for evaluating the second antibody reaction of the conventional assay.25 This resulted in a
change in the minimal detection level of DCP, from
100 to 4 mAU/mL. That study included 115 patients
with early stage HCC whose tumors had a greatest
dimension of less than 2.0 cm and 115 patients with
cirrhosis. It is possible to compare the specificities and
the sensitivities of that study and the current study.
The 95% specificity (with 54 of 57 with cirrhosis showing true-negativity) was much higher than the specificity shown in the trial of Saitoh et al.,25 which was
84% (97 of 115). The sensitivity of 53% (23 of 43) demonstrated in the current study for patients with small
W: Cancer
Sensitive Determination of DCP in Early HCC/Mita et al.
HCCs whose tumors had a greatest dimension of less
than 2 cm was higher than the sensitivity demonstrated by Saitoh et al.,25 which was 39% (45 of 115).
Although the patients with early stage HCC in each
study were selected by different criteria, the sensitivity
of well-differentiated HCC in the current study was
also much higher than the sensitivity of Edmondson’s
Grade 1 in the study of Saitoh et al.25 (71%, 12 of 17,
vs. 24%, 8 of 34).
The second trial involved prolongation of the incubation time for the first antibody reaction. The conventional assay kit recommended a modified procedure with an incubation time of 16 hours at 4 7C, which
increased the minimal detection level from 100 mAU/
mL to 12.5 mAU/mL. However, reliable data were not
always obtained. Accordingly, the sensitive ED-036
assay kit used in the current study was developed. The
basic composition of reagents and antibodies used in
the ED-036 kit was the same as that used in the conventional assay kit. It improved the sensitivity by both
prolonging the first antibody incubation time and
changing the standard DCP solution. The minimal detection level of ED-036 was 10 mAU/mL.
Serum samples from 148 patients were used in the
current study, and these concentrations of DCP were
less than 100 mAU/mL by conventional assay. However, DCP concentrations in samples from 3 of 91 patients with HCC were more than 100 mAU/mL as determined by the current sensitive enzyme immunoassay (Fig. 1). They ranged from 102 to 112 mAU/mL,
and even their maximum concentration was slightly
in excess of 100 mAU/mL. The reason for this contradictory result is unclear, but it is assumed to be within
the allowable range of error.
Serum samples from 57 patients with cirrhosis
were used in the current study, and the absence of
HCC in patients with cirrhosis was essentially determined by several imaging modalities. In our outpatient
clinic, abdominal ultrasonography was performed every 3 months, and computed tomography and magnetic resonance imaging were alternately performed
every 6 months. In addition, determinations of AFP
and DCP were performed every month in turn. Three
and 8 patients with cirrhosis were positive for DCP
(more than 40 mAU/mL, by the sensitive assay) and
positive for AFP (more than 20 ng/mL) in the current
study. However, no evidence of HCC in patients with
cirrhosis was obtained by imaging modalities of the
aforementioned schedule during the subsequent follow-up period, which lasted for longer than 6 months
after the sample collection.
It is well established that DCP shows extremely
low false-positivity in nonneoplastic diseases of the
liver, except in cases of vitamin K deficiency, pro-
/ 7bc2$$1045
04-09-98 16:12:43
cana
1647
longed jaundice, the presence of vitamin K antagonist,
and so on.6,8,26 There is a general principle that an
increment of sensitivity leads to a decrease in specificity. For instance, an increment of AFP was quite specific to the patients with HCC when it was determined
by the method of immunoprecipitation, with a minimal detection level of 10 mg/mL, which was relatively
high. On the contrary, AFP frequently increases in benign liver diseases, such as chronic hepatitis and cirrhosis, when it is determined by a more sensitive
method of radioimmunoassay or enzyme immunoassay than immunoprecipitation. In the current study,
however, an increase in the sensitivity of DCP did not
result in an increment of false-positivity. Accordingly,
several lines of evidence indicate that the measurement of DCP by the current sensitive enzyme immunoassay combined with AFP determination is quite
useful in the early diagnosis of patients with HCC.
REFERENCES
1.
Okuda K and the Liver Cancer Group of Japan. Primary liver
cancer in Japan. Cancer 1980;45:2663–9.
2. Abelev GI. Production of embryonal serum alpha-globulin
by hepatomas: review of experimental and clinical data.
Cancer Res 1968;28:1344–50.
3. O’Conor GI, Tatarinov YS, Abelev GI, Uriel J. A collaborative
study for the evaluation of a serologic test for primary liver
cancer. Cancer 1970;25:1091–8.
4. Nishi S, Hirai H. Radioimmunoassay of alpha-fetoprotein in
hepatoma, other liver diseases and pregnancy. Gann Monogr
1973;14:79–87.
5. Liebman H, Furie BC, Tong MJ, Blanchard RA, Lo K-J, Lee SD, et al. Des-g-carboxy (abnormal) prothrombin as a serum
marker of primary hepatocellular carcinoma. N Engl J Med
1984; 310:1427–31.
6. Okuda H, Obata H, Nakanishi T, Furukawa R, Hashimoto E.
Production of abnormal prothrombin (des-g-carboxy prothrombin) by hepatocellular carcinoma: a clinical and experimental study. J Hepatol 1987;4:357–63.
7. Fujiyama S, Morishita T, Hashiguchi O, Sato T. Plasma abnormal prothrombin (des-g-carboxy prothrombin) as a
marker of hepatocellular carcinoma. Cancer 1988;61:1621–
8.
8. Hattori N, Ohmizo R, Unoura M, Tanaka N, Kobayashi K,
and the PIVKA-II collaborative working group. Abnormal
prothrombin measurements in hepatocellular carcinoma. J
Tumor Marker Oncol 1988;3:207–16.
9. Yumoto Y, Jinno K, Tokuyama K, Ishimitsu T, Maeda H,
Konno T, et al. Hepatocellular carcinoma detected by iodized oil. Radiology 1985;154:19–24.
10. Schwerk WB, Schmitz-Moormann P. Ultrasonically guided
fine-needle biopsies in neoplastic liver diseases: cytohistologic diagnosis and echo pattern of lesions. Cancer
1981;48:1469–77.
11. Noguchi S, Yamamoto R, Tatsuta M, Kasugai H, Okuda S,
Wada A, et al. Cell features and patterns in fine-needle aspirate of hepatocellular carcinoma. Cancer 1986;58:321–8.
12. Majima Y, Fujimoto T, Iwai I, Tanaka M, Abe M, Abe H, et
al. Histological diagnosis of hepatocellular carcinoma by a
new technique of ultrasound-guided fine-needle biopsy [in
Japanese]. Acta Hepatol Jpn 1988;29:628–36.
W: Cancer
1648
CANCER May 1, 1998 / Volume 82 / Number 9
13. Shinagawa T, Ohto M, Kimura K, Tsunetomi S, Morita M,
Saisho H, et al. Diagnosis and clinical features of small hepatocellular carcinoma with emphasis on the utility of realtime ultrasonography: a study in 51 patients. Gastroenterology 1984;86:495–502.
14. Karvountzis GG, Redeker AG. Relation of alpha-fetoprotein
in acute hepatitis to severity and prognosis. Intern Med
1974;80:156–60.
15. Chen D-S, Sung J-L. Serum alpha-fetoprotein in hepatocellular carcinoma. Cancer 1977;40:779–83.
16. Alpert E, Feller ER. Alpha-fetoprotein (AFP) in benign liver
diseases: evidence that normal liver regeneration does not
induce AFP synthesis. Gastroenterology 1978;74:856–8.
17. Aoyagi Y, Suzuki Y, Isemura M, Soga K, Ozaki T, Ichida T,
et al. Differential reactivity of alpha-fetoprotein with lectins
and evaluation of its usefulness in the diagnosis of hepatocellular carcinoma. Gann 1984;75:809–15.
18. Aoyagi Y, Suzuki Y, Isemura M, Nomoto M, Sekine C, Igarashi K, et al. The fucosylation index of alpha-fetoprotein and
its usefulness in the early diagnosis of hepatocellular carcinoma. Cancer 1988;61:769–74.
19. Aoyagi Y, Isemura M, Suzuki Y, Sekine C, Soga K, Ozaki
T, et al. Fucosylated alpha-fetoprotein as marker of early
hepatocellular carcinoma. Lancet 1985;ii:1353–4.
20. Taketa K, Sekiya C, Namiki M, Akamatsu K, Ohta Y, Endo
Y, et al. Lectin-reactive profiles of alpha-fetoprotein charac-
/ 7bc2$$1045
04-09-98 16:12:43
cana
21.
22.
23.
24.
25.
26.
terizing hepatocellular carcinoma and related conditions.
Gastroenterology 1990;99:508–18.
Aoyagi Y, Isemura M, Yosizawa Z, Suzuki Y, Sekine C, Ono T,
et al. Fucosylation of serum alpha-fetoprotein with primary
hepatocellular carcinoma. Biochim Biophys Acta 1985;
830:217–.
Aoyagi Y, Suzuki Y, Igarashi K, Saitoh A, Oguro M, Yokota
T, et al. Carbohydrate structures of human alpha-fetoprotein
of patients with hepatocellular carcinoma: presence of fucosylated and non-fucosylated triantennary glycans. Br J Cancer 1993;67:486–92.
Watanabe K, Naraki T, Yokoo T, Yamane S, Saitoh S, Okuda
H, et al. Development of sensitive enzyme-immunoassay
kit of PIVKA-II (ED 036) [in Japanese]. Rinshou to Kenkyu
1996;73:1476–81.
Takatsu K, Nakanishi T, Watanabe K, Okuda H, Hayashi N.
Development of sensitive enzyme-immunoassay kit of
PIVKA-II (ED 036). 2nd report. Evaluation of diagnostic ability. Rinshou to Kenkyu 1997;74:2137–41.
Saitoh S, Ikeda K, Koida I, Tsubota A, Arase Y, Chayama K,
et al. Serum des-gamma-carboxyprothrombin concentration determined by the avidin-biotin complex method in
small hepatocellular carcinomas. Cancer 1994;74:2918–23.
Soga K, Arai F, Tsuruya T, Aikawa K, Toshima M, Shibasaki
K, et al. Studies on factors affecting plasma PIVKA-II levels in
hepatocellular carcinoma. Acta Med Biologica 1993;41:197–200.
W: Cancer
Документ
Категория
Без категории
Просмотров
4
Размер файла
87 Кб
Теги
ext2, patients, exostoses, loci, hereditary, karyotypic, abnormalities, ext1, chromosome, multiple, 11p11, clonal, osteochondromas, sporadic, 8q24
1/--страниц
Пожаловаться на содержимое документа