Biomedical subjects

Yoshio Endo

Publications and source records attributed to Yoshio Endo.

At least 19 recordsLinked to original sources

PubMed2007

Recent advances in the treatment of peritoneal dissemination of gastrointestinal cancers by nucleoside antimetabolites.

Peritoneal dissemination is the most common cause of metastasis from malignancies in the abdominal cavity. There are no standard treatments for peritoneal dissemination and the results are poor. The reasons for this are as follows: (1) no effective chemotherapeutic agents have been identified or developed; (2) surgical cytoreduction has little effect on survival improvement; and (3) the molecular mechanisms of peritoneal dissemination have not been clarified and no therapy against the target molecules has been developed. However, studies on the molecular mechanisms of peritoneal dissemination have elucidated some of the target molecules and the development of new multimodal therapies has also improved survival. Early postoperative intraperitoneal chemotherapy, hyperthermic intraperitoneal perfusion chemotherapy and neoadjuvant intraperitoneal-systemic chemotherapy have been newly developed, and a novel surgical therapy named peritonectomy has been proposed to perform complete cytoreduction of peritoneal dissemination. At present, these approaches appear to be effective therapeutic modalities for peritoneal dissemination. However, TS-1 and capecitabine have shown worthwhile results in recent clinical trials for patients with advanced gastric cancer. We recently found that newly developed antitumor cytosine nucleoside analogs show a survival advantage in peritoneal dissemination models using human cancer cells. These non-fluoropyrimidine nucleosides may potentially help to improve the poor prognosis observed in patients with advanced cancers involving peritoneal dissemination.

Adenocarcinoma↗

PubMed2006

Targeting urokinase-type plasminogen activator and its receptor for cancer therapy.

Cancer invasion and metastasis are highly complex processes and a serine protease urokinase-type plasminogen activator/urokinase-type plasminogen activator receptor system has been postulated to play a central role in the mediation of cancer progression. Of note, malignant tumor urokinase-type plasminogen activator and urokinase-type plasminogen activator receptor levels have been found to vary considerably, and to be related to patient prognosis. In mouse models, the urokinase-type plasminogen activator/urokinase-type plasminogen activator receptor system has been studied extensively as a target for anticancer therapy using a variety of approaches. In this review, we discuss the advances in the various modalities that have been used to target the urokinase-type plasminogen activator/urokinase-type plasminogen activator receptor system, including protein-based and peptide-based drugs, antisense therapy, and RNA interference technology. In particular, preclinical mouse model studies that used human tumor xenografts are reviewed.

Animals↗

PubMed2005

S100A4 regulates E-cadherin expression in oral squamous cell carcinoma.

S100A4 has multiple functions in cell cycle progression and cell motility, and has been implicated in cancer invasion. In this study, we examined the expression of S100A4, E-cadherin and its related proteins in oral squamous cell carcinoma (SCC) cell lines with different invasive phenotypes, grade 4C and 4D. Furthermore, grade 4C OSC-19 cells expressing E-cadherin were transfected with S100A4-expression vector and the expression of E-cadherin-related proteins in the stable clone was examined to elucidate the relationship between S100A4 and E-cadherin. Constitutive over-expression of S100A4 in stable transformant of OSC-19 (OSC-19/S100A4) cells led to down-regulation of E-cadherin and beta-catenin. Furthermore, grade 4D invasive cell lines (HOC313 and TSU) expressing S100A4 mRNA did not express E-cadherin, P-cadherin, and beta-catenin, while gamma-catenin protein was only weakly expressed. Thus, the mRNA expression of E-cadherin was reversely correlated with S100A4 expression in oral SCCs. Interestingly, vascular endothelial growth factor-C was up-regulated in OSC-19/S100A4 cells. In summary, S100A4-mediated regulation of E-cadherin expression may play an important mechanism in invasion and metastasis of oral SCC.

Cadherins↗

PubMed2005

Inhibition of invasion and metastasis in oral cancer by targeting urokinase-type plasminogen activator receptor.

There have been reports of strong correlations between poor prognosis in various cancers and concomitant expression of urokinase-type plasminogen activator (uPA) and its surface receptor (uPAR). We and others have previously shown that the uPA system plays a significant role in a subset of head and neck squamous cell carcinoma. In the present study, we found that uPAR is required for invasion and metastasis of highly malignant oral cancer cells (OSC-19). Treating OSC-19 cells with antisense oligonucleotides (AS) targeting uPAR resulted in a dramatic decrease of uPAR mRNA expression. Furthermore, pretreatment with AS or siRNA targeting uPAR inhibited progression of OSC-19 cells in experimental models. These results suggest that overexpression of uPAR increases the invasiveness and metastasis of OSC-19 cells, and that uPAR is a promising therapeutic target for regulation of progression of oral cancer.

Animals↗

PubMed2005

Role of VEGF-C and VEGF-D in lymphangiogenesis in gastric cancer.

BACKGROUND: The molecular mechanisms of lymphangiogenesis induced by vascular endothelial growth factor (VEGF)-C and VEGF-D in gastric cancer were studied. METHODS: VEGF-C and VEGF-D gene expression vectors were transfected into the gastric cancer cell line KKLS, which did not originally express VEGF-C and VEGF-D, and stable transfectants (KKLS/VEGF-C and KKLS/VEGF-D) were established. The cell lines were inoculated into the subserosal layer of the stomach and subcutaneous tissue of nude mice. RESULTS: VEGF-C and VEGF-D expression in KKLS/VEGF-C and KKLS/VEGF-D cells was found by reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis. Expression of mouse VEGF receptor (VEGFR)-2 and mouse VEGFR-3 mRNA was detected in the KKLS/VEGF-C and KKLS/VEGF-D gastric tumors. Newly formed lymphatic vessels were detected not only in the periphery but also in the center of the tumors. The intratumor lymphatic vessels connected with the preexisting lymphatic vessels in the muscularis mucosa. The average numbers of lymphatic vessels in KKLS/VEGF-C (52.0 +/- 9.5) and KKLS/VEGF-D (16.4 +/- 0.6) gastric tumors were significantly higher than that in the KKLS/control vector tumors (4.0 +/- 1.4). CONCLUSION: VEGF-C and VEGF-D may induce neoformation of lymphatic vessels in experimental gastric tumors by the induction of VEGFR-3 expression.

Animals↗

PubMed2005

In vitro chemosensitivity test for human genito-urinary tumors using collagen gel matrix.

BACKGROUND: Although the aim of chemosensitivity tests is to predict the efficacy of anticancer agents for individual patients, no generally accepted assay has been established. METHODS: A chemosensitivity test was conducted for solid tumors with an organ culture system using collagen gel matrix (CGM). Seventy-five samples of transitional cell carcinoma (TCC), 20 of germ cell tumor (GCT) and 13 of renal cell carcinoma (RCC) were used for the chemosensitivity test, and 20 patients were treated with anticancer drugs on the basis of the test results. RESULTS: Positive rates of anticancer drugs for the 75 TCC samples were 64.9% for carboplatin, 63.4% for cisplatin, 32.1% for etoposide, 19.7% for THP-adriamycin, 16.7% for vinblastine, and 12.3% for methotrexate, indicating that positive rates of the latter three agents consisting of an MVAC regimen were unexpectedly low. The GCT had higher positive rates than the other cancers while RCC had the lowest. In 20 eligible patients (seven patients with bladder tumors and 13 with GCT), the true positive and true negative rates were 42% (5/12) and 75% (6/8), respectively, and the sensitivity and specificity were 71% (5/7) and 46% (6/13), resulting in a 55% (11/20) accurate predictive value. CONCLUSION: Although predictive accuracy was moderate when combination chemotherapy was used, information about chemosensitivity may have some beneficial effect on the treatment of patients with invasive bladder cancer or advanced GCT, because insensitive drugs detected by the test could be deleted or replaced with more sensitive ones.

Antineoplastic Agents↗

PubMed2005

Pharmacokinetic advantage of intraperitoneal injection of docetaxel in the treatment for peritoneal dissemination of cancer in mice.

Intraperitoneal administration of docetaxel has been used to treat peritoneal dissemination of cancer, but its safety has not yet been confirmed. We have compared the pharmacokinetic behaviour of docetaxel after intravenous and intraperitoneal administration in CD-1-nu/nu mice bearing MKN45P, a gastric cancer variant line producing peritoneal dissemination. Docetaxel (8 mg kg(-1)) was intravenously or intraperitoneally injected into the mice and at designated times the drug concentration was measured in plasma, ascites fluid, and abdominal tissues (liver, kidney, intestine and spleen, solid cancer, and suspended free cancer). The pharmacokinetic behaviour of docetaxel was similar in control mice and cancer-bearing mice after administration via either route, except that the transfer of docetaxel from the abdominal cavity to systemic blood (plasma) was slower in cancerbearing mice than in control mice. As expected, the intraperitoneal drug concentration was much higher (approximately 100-fold) and was maintained for a longer time in the intraperitoneal injection group than in the intravenous injection group. The drug concentrations in peritoneal solid cancer tissue and suspended free cancer cells were also significantly higher for a longer time in the intraperitoneal injection group than in the intravenous injection group. The values of the plasma area under concentration-time curves (AUC) were similar for both administration routes. The ratio of AUC ascite/AUC plasma after intraperitoneal administration was higher than after intravenous administration. The drug concentration in abdominal organs after intraperitoneal injection was lower during the first 2 h, then became similar to those after intravenous injection. These results indicated that the intraperitoneal administration of docetaxel for peritoneal dissemination was likely to be an effective treatment method, without causing any increase in systemic toxicity.

Animals↗

PubMed2004

A crucial role of uridine/cytidine kinase 2 in antitumor activity of 3'-ethynyl nucleosides.

The antitumor 3'-ethynyl nucleosides, 1-(3-C-ethynyl-beta-D-ribopentofuranosyl)cytosine (ECyd) and 1-(3-C-ethynyl-beta-D-ribopentofuranosyl)uridine (EUrd), are potent inhibitors of RNA polymerases and show excellent antitumor activity against various human solid tumors in xenograft models. ECyd is being investigated in phase I clinical trials as a novel anticancer drug possessing a unique antitumor action. ECyd and EUrd require the activity of uridine/cytidine kinase (UCK) to produce the corresponding active metabolite. The UCK family consists of two members, UCK1 and UCK2, and both UCKs are expressed in many tumor cells. It was unclear, however, whether UCK1 or UCK2 is responsible for the phosphorylation of the 3'-ethynyl nucleosides. We therefore established cell lines that are highly resistant to the 3'-ethynyl nucleosides from human fibrosarcoma HT-1080 and gastric carcinoma NUGC-3. All the resistant cell lines showed a high cross-resistance to ECyd and EUrd. As a result of cDNA sequence analysis, we found that UCK2 mRNA expressed in EUrd-resistant HT-1080 cells has a 98-base pair deletion of exon 5, whereas EUrd-resistant NUGC-3 cells were harboring the point mutation at nucleotide position 484 (C to T) within exon 4 of UCK2 mRNA. This mutation was confirmed by genome sequence analysis of the UCK2 gene. Moreover, the expression of UCK2 protein was decreased in these resistant cells. In contrast, no mutation in the mRNA or differences in protein expression levels of UCK1 were shown in the EUrd-resistant HT-1080 and NUGC-3 cells. These results suggest that UCK2 is responsible for the phosphorylation and activation of the antitumor 3'-ethynyl nucleosides.

Antineoplastic Agents↗

PubMed2004

Oral administration of uracil-tegafur (UFT) inhibits liver micrometastasis of human colon cancer in an orthotopic nude mouse model and its early detection system.

PURPOSE: To evaluate the effect of UFT (an oral antineoplastic drug combining uracil and tegafur) as an adjuvant chemotherapy. METHODS: We examined whether UFT inhibits micrometastasis of the liver from colon cancer implanted into the cecum of nude mice in an orthotopic model. Moreover, we studied whether our early detection system using a polymerase chain reaction (PCR) of the human beta-globin gene would be useful in this model. RESULTS: The administration of 20 mg/kg UFT p.o., which is a relatively small dose compared with 65 mg/kg of the maximum tolerated dose of this drug in mice, inhibited liver metastasis completely when started immediately after a cecectomy (micrometastasis present at this time), but did not inhibit liver metastasis significantly when started at 4 weeks after a cecectomy (gross tumor present at this time). There were no severe toxicities at this dose. In our PCR study, all livers in 10 mice to which therapy was given immediately after a cecectomy and without liver metastasis showed no PCR-amplified fragment, while 7 of 10 livers in the nontreatment group in which gross liver metastases were not observed demonstrated this fragment. CONCLUSIONS: These findings indicate that UFT is useful for either adjuvant chemotherapy or the inhibition of micrometastasis, and our system to detect micrometastasis by examining the human beta-globin gene is useful for the early evaluation of the efficacy of these drugs.

Administration, Oral↗

PubMed2004

Correlation of S100A4 expression with invasion and metastasis in oral squamous cell carcinoma.

S100A4 is known to be involved in cancer cell motility by virtue of its ability to activate non-muscle myosin. In the current study, we investigated the interrelationship of clinico-pathological findings and S100A4 expression in oral squamous cell carcinoma (SCC). The expression of S100A4 was examined immunohistochemically in 41 clinical specimens of oral SCC. S100A4 expression was detected in 11 (26.8%) of 41 cases. Although the expression of S100A4 was not associated with the primary tumor site and degree of differentiation, there was a significant correlation between the increased S100A4-expression and the mode of invasion (p < 0.0001). In addition, the S100A4 status showed a clear correlation with lymph node metastasis (P < 0.01). These results lead us to conclude that S100A4 expression status may be a useful prognostic factor in patients with invasive and metastatic oral SCCs.

Carcinoma, Squamous Cell↗

PubMed2004

Isolation and expression of five-amino-acid-deleted variant of feline hepatocyte growth factor (HGF) cDNA.

Hepatocyte growth factor (HGF) is a pleiotropic cytokine that stimulates a wide array of cellular targets, including hepatocytes and other epithelial cells, melanocytes, endothelial and hematopoietic cells. We have cloned a different form of cDNA, with a deletion of 15 base pairs predicted to result in the loss of 5 amino acids from the first kringle domain. To investigate the biological activity, original and deleted variant of feline HGF cDNAs were transiently expressed in COS-7 cells. Both recombinant feline HGFs showed almost the same dose-response curves in the stimulation of the growth of BNL CL.2 cells (a mouse hepatocyte cell line) and scatter activity of Madin-Darby canine kidney (MDCK) cells. The findings reported here suggest that the deleted variant of feline HGF has almost the same biological activity as the original in terms of the proliferation and scatter activity.

Animals↗

PubMed2004

[The association of expression and gene polymorphism of the thymidylate synthase gene with 5-fluoro-5'-deoxyuridine sensitivity in gastric cancer cell lines].

Thymidylate synthase (TS) is a target enzyme of 5-fluorouracil (5-FU), and the TS expression level of cancer tissues is a potential predictor of the response to 5-FU-based chemotherapy. The TS gene has a polymorphic tandem-repeat sequence, which is associated with its protein expression. Therefore, the TS polymorphism may also be a predictor of the response to 5-FU-based chemotherapy. In this study, we analyzed the TS genotype, TS protein level, and sensitivity to 5-fluoro-5'-deoxyuridine (5'-dFUrd) in 10 human gastric cancer cell lines. TS genotype was classified into 2R-homozygote (2R/2R, n=3), 3R-homozygote (3R/3R, n=5), and 2R/3R-heterozygote (2R/3R, n=2). The cell lines with 3R/3R showed a significantly higher IC50 value compared to those with 2R/2R or 2R/3R genotype. There was no relationship between TS protein level and 5'-dFUrd sensitivity. However, a statistically significant relationship was revealed between them when the subgroup with the genotypes of 2R/2R or 2R/3R was considered (r=0.815, p<0.05). In this subgroup, the cell lines with higher TS protein showed higher IC50 value for 5'-dFUrd, indicating less sensitivity to 5'-dFUrd. An identical relationship between the TS protein level and IC50 was also observed in the subgroup with 3R/3R genotype, although it did not reach statistical significance (r=0.745, p=0.09). These results suggest that the TS gene polymorphism and TS protein level may be independent predictors for 5-FU-based chemotherapy.

Antimetabolites, Antineoplastic↗

PubMed2004

[Treatment results of peritoneal dissemination from gastric cancer by neoadjuvant intraperitoneal-systemic chemotherapy].

UNLABELLED: No standard treatment exists for peritoneal dissemination from gastric cancer. We reviewed our experience using a novel treatment consisting of peritonectomy and intraoperative chemo-hyperthermic peritoneal perfusion (CHPP). Records of all patients who underwent CHPP and cytoreductive surgery from 1992 to 2001 were reviewed. RESULTS: Data from 107 patients (average age, 52 years) were available. P3 dissemination was found in 72 patients, and 8 and 27 patients showed P1 or P2 dissemination, respectively. Peritoneal metastasis was synchronous in 75 and metachronous in 32 patients. All patients received CHPP after cytoreductive surgery. Peritonectomy was performed in 42 patients. Complete cytoreduction (CC-0) was achieved in 47 patients (44%). Peritonectomy, resulted in CC-0 in 69% (29/42), but CC-0 was achieved in 18 of 65 (28%) patients by ordinary surgical techniques. There were 23 postoperative complications (21%) after operation. The overall operative mortality was 2.8% (3/107). Median follow-up for the entire study group was 46 months. Seventeen patients (15%) were disease-free, and 90 patients were dead at the time of analysis. Eighty-seven deaths were related to progression of disease. The median survival of all patients was 16.2 months, with an actual 5-year survival of 6%. Median survival of CHPP plus ordinary cyoreduction was 12.0 months and that after CHPP and peritonectomy was 22.8 months. Completeness of cytoreduction and peritonectomy were significant prognostic factors on univariate analysis and 5-year survival rate was 27%. Lymph node status, grade of peritoneal dissemination (P1-2 vs P3), age (>60 years vs <60 years), tumor volume of dissemination (>2.5 cm vs <2.5 cm in diameter), and histologic type (differentiated vs. poorly differentiated type) did not affect survival. The cox proportional model demonstrated that completeness of cytoreduction was the strongest prognostic factor. Patients who had an incomplete resection had 2.8-fold higher risk of dying from disease than patients who underwent complete cytoreduction. The 5-year survival after complete cytoreduction was 12%, compared with 2% for incomplete resection. Four patients lived more than 5 years. Cytoreduction was incomplete in one 5-year survivor who showed complete response to CHPP. CONCLUSION: Complete cytoreduction using peritonectomy and CHPP may improve survival of patients with peritoneal dissemination from gastric cancer. This procedure is most appropriate for highly motivated patients who are committed to survive as long as possible.

Analysis of Variance↗

PubMed2003

The molecular targets of antitumor 2'-deoxycytidine analogues.

Most antitumor 2'-deoxycytidine (dCyd) analogues, such as Ara-C (1-beta-arabinofuranosylcytosine) and gemcitabine (2'-deoxy-2',2'-difluolo-cytidine), have common antitumor mechanisms and metabolic pathways. These nucleosides are transported into tumor cells via specific nucleoside transporters (NT), and then phosphorylated toward each monophosphate form by dCyd kinase. Finally, tri-phosphate forms are enzymatically produced and efficiently inhibit DNA synthesis. It is believed that dCyd kinase is a very important activator of antitumor 2'-dCyd analogues and an attractive molecular target for biochemical modulation. Resistant cells established by continuous exposure to 2'-dCyd analogues in vitro have extremely high resistance as compared with parental cells, and their resistance indexes are sometimes increased between several hundred to thousand times. Such high resistance is generally attributed to deficiency of dCyd kinase activity, but the clinical resistance index of Ara-C-resistant patients is estimated to be increased a maximum of 20 times compared with non-treated patients. The differences between experimental and clinical resistances may be caused by different mechanisms of resistance. To clarify such resistance mechanisms, we carried out research focused on NT and dCyd kinase. Our results show that earlier resistant cells, that exhibited a 20 times lower resistance index, had a reduced NT activity but retained dCyd kinase activity. In contrast, dCyd kinase activity was deficient in later resistant cells that showed maximum resistance. Both NT and dCyd kinase activities are important for the acquisition of resistance and are useful as molecular targets for biochemical modulation or the development of novel antitumor 2'-dCyd analogues. These results suggest that NT activity is likely to be responsible for clinical resistance.

Animals↗

PubMed2002

Multifunctional anti-angiogenic activity of the cyclic peroxide ANO-2 with antitumor activity.

Our focus was to develop an anti-angiogenic drug possessing the inhibitory activity of urokinase-type plasminogen activator (u-PA) production. During preliminary screening, the effects of 13 ozonides on the inhibition of u-PA production in human fibrosarcoma HT-1080 cells and on the inhibition of angiogenesis on chicken embryonic chorioallantoic membranes were determined. Of the ozonides tested, 9 inhibited in vitro u-PA production of HT-1080 cells and 7 of these 9 exhibited strong anti-angiogenic activity. Interestingly, 6 of the 13 ozonides also inhibited cathepsin B activity. 1-Phenyl-1, 4-epoxy-1H,4H-naphtho[1,8-de][1, 2]dioxepin (ANO-2) potently inhibited cathepsin B (IC(50) = 0.47 microM) as well as u-PA production. Consequently, ANO-2 was selected for further study. ANO-2 inhibited tube formation by human umbilical vein endothelial cells cultured on Matrigel while exhibiting no cytotoxicity. Additionally, in vivo administration of ANO-2 inhibited angiogenesis induced by mouse Sarcoma-180 cells tested using the mouse dorsal air sac assay. Moreover, ANO-2 also suppressed primary tumor growth and reduced the number of pulmonary metastases caused by Lewis lung carcinoma cells in mice. These in vitro and in vivo activities indicate that ANO-2 has considerable potential as a new and potent anti-angiogenic drug that inhibits both u-PA production and enzymatic activity of cathepsins, indicating that ANO-2 may be a multifunctional inhibitor of angiogenesis.

Air Sacs↗

PubMed2002

K15 protein of Kaposi's sarcoma-associated herpesvirus is latently expressed and binds to HAX-1, a protein with antiapoptotic function.

The Kaposi's sarcoma-associated herpesvirus (KSHV) (or human herpesvirus 8) open reading frame (ORF) K15 encodes a putative integral transmembrane protein in the same genomic location as latent membrane protein 2A of Epstein-Barr virus. Ectopic expression of K15 in cell lines revealed the presence of several different forms ranging in size from full length, approximately 50 kDa, to 17 kDa. Of these different species the 35- and 23-kDa forms were predominant. Mutational analysis of the initiator AUG indicated that translation initiation from this first AUG is required for K15 expression. Computational analysis indicates that the different forms detected may arise due to proteolytic cleavage at internal signal peptide sites. We show that K15 is latently expressed in KSHV-positive primary effusion lymphoma cell lines and in multicentric Castleman's disease. Using a yeast two-hybrid screen we identified HAX-1 (HS1 associated protein X-1) as a binding partner to the C terminus of K15 and show that K15 interacts with cellular HAX-1 in vitro and in vivo. Furthermore, HAX-1 colocalizes with K15 in the endoplasmic reticulum and mitochondria. The function of HAX-1 is unknown, although the similarity of its sequence to those of Nip3 and Bcl-2 infers a role in the regulation of apoptosis. We show here that HAX-1 can form homodimers in vivo and is a potent inhibitor of apoptosis and therefore represents a new apoptosis regulatory protein. The putative functions of K15 with respect to its interaction with HAX-1 are discussed.

Adaptor Proteins, Signal Transducing↗

PubMed2002

[Multidisciplinary therapy for peritoneal dissemination using peritonectomy].

An aggressive approach to peritoneal dissemination involves peritonectomy procedures combined with preoperative intraperitoneal chemotherapy, intraoperative chemo-hyperthermia, and postoperative systemic chemotherapy. We have been performing multimodal therapy consisting of peritonectomy plus perioperative chemotherapy for the treatment of patients with peritoneal dissemination. Fifty-seven patients with established peritoneal dissemination from gastric cancer (n = 32), colon cancer (n = 17), ovarian cancer (n = 7), and mesothelioma (n = 1) have been treated with peritonectomy and intraoperative chemo-hyperthermia. Five-year survival rates of patients with gastric and colon cancer were 18% and 38%, respectively. Among various clinical factors, complete tumor resection was the most significant prognostic factor, and the prognosis of patients who underwent complete cytoreduction was significantly better than those who received incomplete cytoreduction. A multimodal therapy consisting of perioperative chemotherapy and peritonectomy with complete cytoreduction may be the most powerful method to treat patients with established peritoneal dissemination.

Colonic Neoplasms↗

PubMedDate not supplied

Antitumor effect of radioimmunotherapy in a mouse model of testicular tumor with micrometastases defined by polymerase chain reaction.

The efficacy of radioimmunotherapy (RIT) was evaluated by using a mouse model of testicular tumor with macro- and micrometastases to various organs. RIT consisting of a single intravenous injection of 5.8 MBq of I-131-labeled anti-placental alkaline phosphatase (PLAP) MAb was conducted one day or 7 days after testicular implantation in SCID mice of HeLa Hep2 cells expressing PLAP. RIT antitumor effect was significant for primary tumors as well as micrometastases defined by polymerase chain reaction (PCR) assay. However, ablation of tumor cells could be achieved with this treatment only at the initial stage of tumor growth in the testis, when metastasis could also be prevented. Once micrometastasis had occurred, however, complete elimination of tumor cell(s) was difficult. These findings appear to have implications for the use of RIT in treatment for micrometastasis, especially when detectable only by PCR assay.

Adenocarcinoma↗