Biomedical subjects

H Sakahara

Publications and source records attributed to H Sakahara.

At least 55 records · Page 3Linked to original sources

PubMed1999

Radioimmunotherapy for liver micrometastases in mice: pharmacokinetics, dose estimation, and long-term effect.

The pharmacokinetics of a therapeutic dose of 131I-labeled antibody and the absorbed dose in liver micrometastases of human colon cancer LS174T in female BALB/c nu/nu mice were investigated, along with the long-term therapeutic effect. Mice with liver micrometastases were given an intravenous injection of 131I-labeled anti-carcinoembryonic antigen (CEA) antibody F33-104 (8.88 MBq/ 40 microg). The biodistribution of the antibody was determined 1, 2, 4, 6, and 10 days later. The absorbed dose was estimated for three hypothetical tumor diameters; 1,000, 500, and 300 microm. Autoradiography showed a homogeneous distribution of radioactivity in the micrometastases, and a high uptake was maintained until day 6 (24.0 % injected dose (ID)/g on day 1 to 17.8 %ID/g on day 6), but decreased thereafter. The absorbed doses in the 1,000-, 500-, and 300-microm tumors were calculated to be 19.1, 12.0, and 8.2 Gy, respectively. The intravenous injection of the 131I-labeled antibody also showed a dose-dependent therapeutic effect (all mice of the nontreated group died, with a mean survival period of 4 weeks; 3 of the 8 mice that received 9.25 MBq survived up to 120 days with no sign of liver metastasis). These data give further evidence that micrometastasis is a good target of radioimmunotherapy, and that an absorbed dose of less than 20 Gy can effectively control small metastatic lesions.

Animals↗

PubMed1999

The relationship of glycosylation and isoelectric point with tumor accumulation of avidin.

UNLABELLED: Radiolabeled avidin markedly accumulated in intraperitoneal tumors and was cleared rapidly from circulation when given intraperitoneally. This study investigated the mechanisms of the tumor localization of avidin. METHODS: Avidin was deglycosylated through endoglycosydase-H digestion and/or neutralized by acetylation of its lysine amino acids with acetic acid N-hydroxysuccinimide ester. Avidin and modified avidins were analyzed using sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS/PAGE) and isoelectric focusing. A tumor model was established by intraperitoneal injection of human colon cancer cells, LS180, in nude mice. Avidin and modified avidins were labeled with 111In using diethyleneamine pentaacetic acid-biotin and were administered intraperitoneally into the tumor-bearing mice. The biodistribution of radioactivity was examined 2 and 24 h postinjection. RESULTS: Deglycosylated avidins revealed a major band of smaller molecules on SDS/PAGE. The isoelectric point of neutralized avidins was reduced to less than 5, whereas that of unneutralized avidins was more than 9.5. Biodistribution study demonstrated that liver uptake was decreased by deglycosylation and kidney accumulation was decreased by neutralization, respectively. The blood clearance was remarkably slowed by combined modification of deglycosylation and neutralization. The tumor uptake of radioactivity was reduced by either deglycosylation or neutralization and was further decreased with combined modification. CONCLUSION: Both high glycosylation and positive charge of avidin contributed to its accumulation in tumor. This study may facilitate development of a new vehicle for the delivery of therapeutic agents to intraperitoneal tumors.

Animals↗

PubMed1999

Intratumoral distribution of radiolabeled antibody and radioimmunotherapy in experimental liver metastases model of nude mouse.

UNLABELLED: The biodistribution and intratumoral distribution of radiolabeled anticarcinoembryonic antigen (CEA) monoclonal antibody in experimental liver metastases and the therapeutic effect of 131I-labeled anti-CEA antibody on the metastases were studied. METHODS: Three weeks after an intrasplenic injection of human colon cancer cells, mice received an intravenous injection of 125I- or 111In-labeled anti-CEA antibody F33-104. The biodistribution and tumor penetration of radiolabeled antibody were examined by using quantitative autoradiography. To evaluate the therapeutic effect, 5.55, 9.25 or 11.1 MBq (150, 250 or 300 microCi) 131I-labeled F33-104 were injected into groups of mice that had micrometastases smaller than 1 mm. Control groups were injected with phosphate-buffered saline or 131I-labeled control antibody. Mice were killed 3 wk later to determine the size of liver metastases. RESULTS: 1251-labeled F33-104 showed a high accumulation in the liver metastases (percentage of injected dose per gram of metastases [%ID/g] >24%, metastasis-to-liver ratio >9.8, metastasis-to-blood ratio >2.1); however, its accumulation was heterogeneous or peripheral in the nodules more than 1 mm in diameter. When the antibody dose was increased, antibody penetration was improved, but tumor uptake of radioactivity and specificity ratios decreased. In mice with large metastases, radioactivity in the normal tissue was lower than that in mice with small metastases, resulting in higher metastasis-to-background ratios. 111In-labeled antibody showed even higher tumor uptake than 125I-labeled antibody (>51 %ID/g). Metastases formation was suppressed in a dose-dependent manner by 131I-labeled F33-104 injection (5 of 8 mice had no macroscopic tumor after an injection of 5.55 MBq (150 microCi), and all mice had no visible metastasis after an injection of 9.25 or 11.1 MBq [250 or 300 microCi]), whereas tumor progression was seen in the control groups. CONCLUSION: Liver metastases had easy accessibility to the antibody. Micrometastases of less than 0.5 mm in diameter showed homogeneous intratumoral distribution of injected antibody and were successfully treated with 131I-labeled antibody. Very high uptake and satisfactory metastasis-to-liver ratios with 111In-labeled antibody suggest that the use of a radiometal with high beta-energy, such as 90Y or 188Re, is preferable for the successful radioimmunotherapy of metastases larger than 1 mm.

Animals↗

PubMed1999

Evaluation of intraoperative radiation therapy for unresectable pancreatic cancer with FDG PET.

UNLABELLED: This investigation was undertaken to evaluate 18F-labeled fluorodeoxyglucose (FDG) PET in monitoring patients after intraoperative radiotherapy (IORT) for unresectable pancreatic cancer and to compare its usefulness with CT. METHODS: FDG PET was performed in 12 consecutive unresectable ductal adenocarcinoma patients before (n = 12) and after IORT (0.7-11.9 mo, n = 14). In the follow-up period, FDG PET results after IORT were divided into three groups: early (0-2.0 mo after IORT, n = 7), intermediate (2.1-4.0 mo, n = 5) and delayed period (4.1 mo or later, n = 2). FDG uptake at 60 min after injection of 185 MBq FDG under fasting conditions was analyzed with standardized uptake value (SUV). Three parameters, the highest SUV in the tumor, the area of tumor showing SUV of more than 2.0 and the average SUV in the tumor area were calculated. Ratios of each parameter after IORT to that before IORT were defined as residual uptake ratio (RUR)-1, -2 and -3, respectively. Tumor regression after IORT was evaluated with CT as tumor size ratio (TSR) every 2 mo. RESULTS: Results of RUR-1 and -3 were consistent with tumor size measured by CT. They decreased in 10 patients with partial response and increased in 2 patients with no change, although these 2 patients had abscesses. RUR-3 decreased consistently as 0.65+/-0.33 in 2 mo, 0.51+/-0.39 in 4 mo and 0.24 in 4 mo or later after IORT, respectively. RUR-1 decreased in early period, but demonstrated no change through the remaining periods. There were discrepancies between the results of RUR-2 and those of the other RURs. CT results revealed a slow decrease in tumor size, because TSR was 0.91 +/-0.10, 0.76+/-0.11 and 0.70+/-0.18 in 2, 4 and 6 mo after IORT, respectively. RUR-3 was smaller than TSR at 2 mo (P < 0.05) and 4 mo (P = 0.056). These results indicate that the measurement of the average SUV in the tumor area with FDG PET could evaluate the local response of pancreatic cancer after IORT earlier and more markedly than with CT. CONCLUSION: FDG PET was useful in monitoring patients after IORT, because the decrease of metabolism in pancreatic tumor could be detected earlier than the decrease in tumor size.

Adenocarcinoma↗

PubMed1999

Asialoglycoprotein receptor scintigraphy in evaluation of auxiliary partial orthotopic liver transplantation.

UNLABELLED: The purpose of this study was to evaluate asialoglycoprotein receptor scintigraphy in the post-transplant monitoring of liver graft and native liver functions in recipients of auxiliary partial orthotopic liver transplantation (APOLT) from living donors. METHODS: We performed 36 asialoglycoprotein receptor scintigraphies on 13 patients who had undergone APOLT for noncirrhotic metabolic liver diseases or for small-for-size grafts. The portal vein of the native liver was separated in 12 patients. Anterior dynamic images including the heart and both livers were obtained for 16 min after intravenous injection of 99mTc-diethylenetriamine pentaacetic acid-galactosyl human serum albumin (GSA), and thereafter static SPECT images of both livers were obtained. Uptake rates from the blood to the graft and to the native liver were determined separately by Patlak plot graphical analysis. Relative uptake of GSA by the graft was calculated from transverse SPECT images. The relative volume of the graft liver was determined by CT. RESULTS: The relative uptake of GSA by the graft was higher or increased more rapidly than the relative volume of the graft in 8 of 11 patients with no severe complications concerning the graft. The relative uptake by severely damaged graft liver in 2 patients was much lower than the relative volume. The uptake rate of GSA by the graft was low in these 2 patients. The uptake rate by the native liver decreased when the portal vein was separated. CONCLUSION: The relative uptake of GSA was a better indicator of graft liver function than was anatomic volume. The uptake rate provided additional independent information of each liver. Asialoglycoprotein receptor scintigraphy is useful for distinguishing and monitoring the graft and native liver functions in patients who had undergone APOLT.

Adolescent↗

PubMed1998

Avidin targeting of intraperitoneal tumor xenografts.

BACKGROUND: Lectins (proteins that bind specific sugar molecules on glycoproteins and glycolipids) are expressed at various levels on the surface of tumor cells. Conjugation of cytotoxic agents to glycoproteins recognized by lectins could be useful in the treatment of tumors. Avidin (a highly glycosylated, positively charged protein found in egg white) contains terminal N-acetylglucosamine and mannose residues that bind to some lectins. In this study, we tested the ability of avidin, labeled through conjugation to radioactive biotin (a B vitamin), to target intraperitoneal tumors. METHODS: Biotin was radioactively labeled with 111In. Four tumor models (one ovarian, one lung, and two colon) were established in nude mice by intraperitoneal injection of cultured cancer cells. The following two approaches were used in the intraperitoneal administration of avidin: 1) radioactive biotin-avidin conjugates were injected and 2) avidin was injected 1-24 hours before the injection of radioactive biotin (avidin pretargeting; avidin-biotin conjugates formed in vivo). The distribution of injected radioactivity in the tissues of treated animals was assessed. RESULTS: Radiolabeled avidin localized highly and rapidly in the tumors. More than 50% of the administered dose of avidin-biotin conjugate accumulated per gram of tumor tissue 2 hours after injection; high tumor uptake of radioactivity was observed up to 24 hours after conjugate injection. In contrast, accumulation of radioactivity in normal tissues was low, yielding high tumor to nontumor ratios. With avidin pretargeting, accumulation of radioactivity in the liver, kidney, and spleen was reduced to a greater extent than that in the tumor, and tumor to nontumor ratios were increased. CONCLUSIONS: Avidin may be a promising vehicle for the delivery of radioisotopes, drugs, toxins, or therapeutic genes to intraperitoneal tumors.

Animals↗

PubMed1998

Imaging of intraperitoneal tumors with technetium-99m GSA.

99mTc labeled galactosyl serum albumin (GSA) has been used clinically as a receptor-binding agent for the assessment of liver function. The aim of this study was to investigate the usefulness of 99mTc-GSA in intraperitoneal (i.p.) tumor imaging. A tumor model was established by i.p. inoculating nude mice with human ovarian cancer cell SHIN-3, or colon cancer cell LS 180. Radiolabels were i.p. injected into the tumor-bearing mice and the biodistribution of radioactivity was examined. After administration, 99mTc-GSA rapidly accumulated in the tumor. The tumor uptake was 5.82-8.46 %ID/g from 30 min to 6 h after the injection. Radioactivity in the blood was very low, less than 0.3 %ID/g, resulting in high tumor-to-blood ratio. Tumors could be clearly seen by scintigraphic imaging. Accumulation of i.p.-injected 99mTc labeled human serum albumin (HSA) in i.p. tumors was similar to that of 99mTc-GSA, but radioactivity of 99mTc-HSA in the circulation was high, resulting in a significantly lower tumor-to-blood ratio. In conclusion, 99mTc-GSA, when i.p. injected, accumulated in i.p. tumors and cleared from circulation rapidly, which would make it useful for the imaging of i.p. tumors.

Animals↗

PubMed1998

Gastrinoma with multiple liver metastases: effectiveness of dacarbazine (DTIC) therapy.

Gastrinoma when associated with liver metastasis results in markedly reduced survival. However, a standard chemotherapeutic protocol for patients with unresectable tumors has not been established. We treated two patients with gastrinoma with multiple liver metastases with intravenous administration of 5-dimethyltriazenoimidazole-4-carboxamide (DTIC; dacarbazine) at a dose of 200 mg/body for 5 consecutive days. The first patient showed a marked decrease in serum gastrin levels, from 338 000 pg/ml to 22 900 pg/ml (normal range, >220pg/ml), as well as a decrease in the size and number of peripancreatic and liver tumors, after four courses of DTIC. An additional nine courses of the treatment were given, and the peripancreatic tumor was resected. The patient has been in good overall condition for more than 3(1/2) years. The second patient was treated with a total of ten courses of DTIC. Serum gastrin levels did not increase and the hepatic tumor did not change in size for more than 4 years. DTIC was effective in controlling the clinical and biochemical manifestations of gastrinoma associated with liver metastasis without serious side effects. As the toxity of DTIC is minimal, (e.g., nausea and vomiting) DTIC therapy should be considered useful for islet cell carcinomas with multiple metastases.

Aged↗

PubMed1998

Three-step tumor imaging with biotinylated monoclonal antibody, streptavidin and 111In-DTPA-biotin.

The purpose of this study was to test the three-step targeting of tumors in mice using biotinylated antibody, streptavidin and radiolabeled biotin. Nude mice bearing subcutaneous LS180 human colon cancer xenografts were intravenously administered with 200 microg of the biotinylated anti-Tn monoclonal antibody MLS128, and 2 days later they got intravenous injection of 50 microg of streptavidin. They were intravenously injected 1, 4 or 7 days later with 0.5 microg of 111In-diethylenetriamine pentaacetic acid (DTPA)-biotin. The tumor uptake, determined 2 h later, was 1.4, 0.5 and 0.6% injected dose/gram of tissue (ID/g), respectively, and the blood radioactivity was 1.0, 0.2 and 0.2% ID/g, respectively. When the interval between the streptavidin and radiolabeled biotin injections was prolonged from 1 day to 7 days, the tumor-to-blood ratio 2 h after injection of 111In-labeled biotin increased from 1.5 to 4.0. Clear tumor images were obtained as early as 2 h after injection of radiolabeled biotin. In conclusion, these preliminary data suggested that the three-step method using the streptavidin-biotin system would be applicable in an experimental mouse tumor model and provides images of tumors rapidly and clearly after injection of radiolabeled biotin.

Animals↗

PubMed1998

Effect of administration route and dose of streptavidin or biotin on the tumor uptake of radioactivity in intraperitoneal tumor with multistep targeting.

The effect of the administration route and dose of streptavidin or biotin on the biodistribution of radioactivity in multistep targeting was studied in nude mice bearing intraperitoneal (IP) colon cancer xenograft. The multistep targeting included a two-step method using biotinylated antibody and radiolabeled streptavidin and a three-step method with radiolabeled biotin based on the two-step method. A monoclonal antibody, MLS128, which recognizes Tn antigen on mucin, was biotinylated and injected intravenously (i.v.) or i.p. in nude mice bearing human colon cancer LS180 IP xenografts for pretargeting. In the two-step method, i.p.-injected streptavidin showed a higher tumor uptake and tumor-to-nontumor ratios than i.v.-injected streptavidin regardless of administration route of pretargeting. The tumor uptake of radiolabeled streptavidin was increased with a high dose of biotinylated antibody pretargeting, but decreased with an increasing dose of streptavidin. In the three-step targeting, i.p. injection also gave a higher tumor uptake of radiolabeled biotin than i.v. injection. In conclusion, i.p. administration of radiolabeled streptavidin or biotin resulted in more efficient IP tumor targeting with the multistep methods.

Animals↗

PubMed1998

Increased streptavidin uptake in tumors pretargeted with biotinylated antibody using a conjugate of streptavidin-fab fragment.

Radiolabeled streptavidin accumulated in tumors pretargeted with biotinylated antibody. However, the absolute delivery of radioactivity was limited. To increase the tumor uptake of radioactivity further, we conjugated streptavidin with a mouse monoclonal antibody (MAb) fragment, OST6Fab, which recognizes antigen on human osteosarcoma. Another mouse MAb, OST7, which also reacts with the same tumor but recognizes an epitope different from the OST6 epitope, was biotinylated. The radioiodinated streptavidin-OST6Fab conjugate was administered to tumor-bearing mice after the biotinylated OST7 pretargeting. The uptake of the conjugate in tumors pretargeted with the biotinylated antibody was significantly higher than that of streptavidin and that of the conjugate of streptavidin and irrelevant Fab fragment. Renal uptake of radioactivity was decreased markedly, and the blood clearance was retarded by the conjugation with Fab fragment. In conclusion, the conjugate of streptavidin with specific Fab fragment increased the accumulation of radioactivity in tumors pretargeted with biotinylated antibody.

Animals↗

PubMed1998

A radioiodinated biocytin derivative for in-vivo applications.

Radioiodinated biocytin derivatives are potentially useful for multi-step tumour targeting using the avidin-biotin system. We synthesized a radioiodinated biocytin derivative and evaluated its properties in vivo. We labelled biocytin with 125I by coupling biocytin to radioiodinated N-succinimidyl 3-(tri-n-butyl-stannyl) benzoate, and assessed its binding to avidin and its biodistribution in normal and tumour-bearing mice. When the synthesized biocytin was incubated with immobilized avidin, more than 94% of the radioactivity was bound. However, after 2 h incubation in serum, only 40% of the radioactivity was bound to the avidin. The iodinated biocytin derivative was characteristically taken up by the liver and the kidneys when injected intravenously into mice. In mice bearing an intraperitoneal tumour xeno-graft, 125I-biocytin and 111In-biotin were co-injected intraperitoneally 4 h after the intraperitoneal administration of avidin, which accumulated in the intraperitoneal tumours. At 2 and 24 h, the tumour uptake of 125I-biocytin was 8.2 and 3.8% ID/g respectively, whereas that of 111In-biotin was 20.0 and 18.7% ID/g respectively. When radioiodinated, biocytin retains its binding capacity to avidin, and it localizes well with high tumour-to-normal tissue ratios early post-injection using the two-step method, but compared to 111In-biotin it is unstable. We conclude that the stability of the product in serum needs to be improved prior to in-vivo applications.

Animals↗

PubMed1998

Improved intratumoral penetration of radiolabeled streptavidin in intraperitoneal tumors pretargeted with biotinylated antibody.

UNLABELLED: Inefficient intratumoral penetration of pharmaceuticals is one of the major limiting factors against effective tumor-targeting therapy. This study investigated the effect of the distribution pattern of the binding site in tumors on the penetration of target material. METHODS: In the first experiment, radiolabeled biotinylated monoclonal antibody, MLS128, was injected intraperitoneally or intravenously into nude mice bearing intraperitoneal human colon cancer xenografts. In the second experiment, radiolabeled streptavidin was injected intraperitoneally in the tumor-bearing mice after the pretargeting with the unlabeled biotinylated antibody. Intratumoral distribution of radioactivity was examined with quantitative autoradiography. RESULTS: There was no difference in the biodistribution of biotinylated antibody between intraperitoneal and intravenous administrations, but autoradiography showed a higher uptake in the margin and a lower uptake in the center of radioactivity in tumor nodules with intraperitoneal injection and a more uniform intratumoral radioactivity distribution with intravenous injection. In the two-step method, radioactivity in a low dose of streptavidin with intraperitoneal pretargeting primarily localized at the tumor margin. By increasing the dose, streptavidin penetrated more deeply. In tumors with intravenous pretargeting, a more uniform intratumoral distribution of streptavidin was obtained. The biodistribution of radiolabeled streptavidin was the same between different pretargeting routes. CONCLUSION: The better intratumoral penetration of radiolabeled streptavidin after intravenous pretargeting than intraperitoneal pretargeting with biotinylated antibody may be the result of different intratumoral distribution of the binding site for the radiolabel.

Animals↗

PubMed1998

Resting and acetazolamide-challenged technetium-99m-ECD SPECT in transient global amnesia.

Regional resting cerebral blood flow and vascular reserve in a patient with transient global amnesia (TGA) were evaluated during and after a TGA episode using 99mTc-ethyl cysteinate dimer (ECD). The patient had consecutive SPECT studies before and after acetazolamide (ACZ) administration with adjunctive radionuclide angiography using equal-volume-split 99mTc-ECD. SPECT study during TGA episode showed poor vasodilatory reactivity to ACZ in the left medial temporal region involving the hippocampus and resting hypoperfusion in the regions bilaterally. The resting hypoperfusion with reserved vasodilatory reactivity to ACZ also was seen in the bilateral thalami. Abnormal findings in these regions disappeared on the follow-up SPECT study 15 days after the onset. No previous SPECT evaluation of regional abnormalities of both hemodynamic reserve and resting perfusion during and after an episode of TGA has been reported.

Acetazolamide↗

PubMed1998

FDG uptake, GLUT-1 glucose transporter and cellularity in human pancreatic tumors.

UNLABELLED: We previously reported that grading of GLUT-1 glucose transporter expression was related closely to FDG accumulation in FDG PET in human cancers. But in this strong GLUT-1 expression group, there was an enormous range of standardized uptake values (SUVs) within them. METHODS: To evaluate other factors determining the FDG PET uptake, FDG PET was performed in 36 preoperative patients (mean age 62.0 yr) suspected of having pancreatic tumors, including 33 malignant and 3 benign neoplastic tumors. FDG uptake at 50 min after injection of 185 MBq 18F-FDG with > 5 hr fasting condition was semiquantitatively analyzed as SUVs. The GLUT-1 expression was studied by immunohistochemistry of paraffin sections from these tumors after the operation using the antiGLUT-1 antibody. The number of tumor cells within a 5- x 5-mm square was counted manually using x200 magnification photographs and was graded immunohistochemically as strong, weak or negative. RESULTS: In all 36 cases there were 3 cases of GLUT-1 negative, 8 of GLUT-1 weak positive and 25 of GLUT-1 strong positive. In all cases, the total number of tumor cells had no significant value for SUVs. Among 33 GLUT-1 positive cases, the number of GLUT-1 positive tumor cells correlated significantly with SUVs (p < 0.01). Only in 25 strong grade cases, the number of GLUT-1 strong positive tumor cells had a more significant value for SUVs (p < 0.005). Computational multivariate analysis using multiple regression for SUVs was performed evaluating the five variables as follows: tumor size, GLUT-1 immunohistochemical grading, number of total tumor cells, number of total GLUT-1 positive tumor cells and number of GLUT-1 strong positive cells. This analysis revealed that only the variable, the number of GLUT-1 strong positive cells, had a significant regression coefficient for SUVs (standard regression coefficient = 0.855, p < 0.0001). CONCLUSION: These data indicate that GLUT-1 expression plays an essential role in higher FDG accumulation in pancreatic tumor FDG PET, and the cellularity has a significant influence on SUVs only in the condition of GLUT-1 strong positive expression.

Adenocarcinoma↗

PubMed1997

Technetium-99m (V)-dimercaptosuccinic acid: normal accumulation in the breasts.

Technetium-99m (V)-dimercaptosuccinic acid (DMSA) is a tumour-imaging agent which has been used to evaluate medullary thyroid cancer and soft tissue tumours. Physiological uptake has been demonstrated in the kidneys, nasal mucosa and blood pool. In addition to positive accumulation in these sites, uptake in the breasts has been noted. The purpose of this retrospective study was to evaluate the accumulation of 99mTc (V)-DMSA in the normal breasts of 83 patients. There was no accumulation in male breasts. On the other hand, 24 of 51 female patients showed bilateral symmetrical accumulation in the breasts. Positive uptake was seen in 16 of 23 patients (70%) between 15 and 50 years old, but in only 7 of 25 (28%) above 50 years old. One out of three patients (33%) under 15 years old showed positive breast uptake. In conclusion, the female breasts should be included in the description of a pattern of normal biodistribution of 99mTc (V)-DMSA.

Adolescent↗

PubMed1997

Cytokeratin 19 fragment in serum and tissues of patients with pancreatic diseases.

CONCLUSION: The present study has shown that increased serum levels of cytokeratin 19 fragment reflect increases in the size of the pancreatic carcinomas, although the sensitivity for detecting small pancreatic carcinomas was low. BACKGROUND: Cytokeratin is a member of the intermediate family of filaments in epithelial cells. The cytokeratin 19 fragment is an acidic cytokeratin, which is found in various epithelial tissues. Recently, the serum fragment of cytokeratin 19 has been measured and found to be a good marker for squamous cell carcinoma. Cytokeratin 19 is known to be expressed in normal pancreatic tissues and pancreatic carcinomas. However, serum cytokeratin 19 levels in pancreatic diseases have not been precisely detailed. METHODS: In this study, we evaluated serum cytokeratin 19 levels and the immunohistochemical expression of cytokeratin 19 in various pancreatic diseases. RESULTS: Serum cytokeratin 19 levels were high (> 2 ng/mL) in 51 of 99 (52%) cases of pancreatic duct cell carcinoma, but were low in all 24 cases of chronic pancreatitis and in 7 cases of islet cell tumors. The sensitivity of the cytokeratin 19 assay increased with increased size of the pancreatic carcinomas, but was not influenced by the presence of obstructive jaundice. Immunohistochemical studies using a monoclonal anticytokeratin 19 antibody showed that staining for cytokeratin was positive in all 38 of the pancreatic carcinomas examined and in 2 of 6 islet tumors.

Biomarkers, Tumor↗

PubMed1997

Binding of a human monoclonal antithyroglobulin antibody to cultured human thyroid cancer cells.

To develop a new method of radioimmunodetection for thyroid cancer, we tested the binding ability of a human antithyroglobulin monoclonal antibody, VB5, to primary culture of human thyroid cancer cells. VB5 was able to immunostain cytoplasmic thyroglobulin (Tg) in the acetone-fixed cancer cells when used in a labeled streptavidin-biotin method but not in a conventional indirect immunoperoxidase technique. The antibody was readily labeled with I-125 in the standard chloramin-T method, and showed specific binding to the antigen on cultured malignant thyrocytes displaceable with non-labeled VB5 or with excess Tg antigen. Although these initial results in vitro are encouraging, the observed low specific binding (about 1% at room temperature) to intact cells with a single monoclonal antibody seems insufficient to conduct any in vivo immunolocalization experiments in animals. To obtain more binding, we would need a cocktail of several monoclonal antibodies to different epitopes, and also fragmentation of antibody molecules to penetrate into cytoplasm.

Antibodies, Monoclonal↗