False-positives in immunoscintigraphy.
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Aged↗
Biomedical subjects
S Kodaira
Publications and source records attributed to S Kodaira.
[Antitumor activity and toxicity of KB-5424 R, a newly developed antitumor platinum compound].
KB-5424 (ab-(3-aminopyrrolidine)-cd-[glycolato (2-)-0, 0'] platinum (II) is a newly developed antitumor platinum compound which was synthesized at Kanebo Institute for Cancer Research. When the antitumor activity of KB-5424 was evaluated using several rodent tumors, no significant differences were observed between the antitumor activities of KB-5424, cisplatin (CDDP) and DWA-2114 R (DWA). KB-5424 was divided into two kinds of optical isomers, KB-5424 R and KB-5424 S, of which antitumor activity was compared each other. The maximum increased life span (ILSmax) on L 1210 of KB-5424 R was almost equal to that of CDDP and better than those of KB-5424 S and carboplatin (CBDCA). The antitumor activity of KB-5424 R on a human tumor xenograft MX-1 was almost identical to those of CDDP and CBDCA and better than that of DWA. Since the nephrotoxicity of KB-5424 R was significantly reduced comparing with CDDP, this newly developed antitumor platinum compound was thought to be a promising agent for the clinical application.
Animals↗
[The preoperative and postoperative carcinoembryonic antigen test in the diagnosis, staging, and prognosis of gastric cancer. Tumor Marker Committee, Japanese Foundation for Multidisciplinary Treatment of Cancer].
Preoperative and postoperative carcinoembryonic antigen (CEA) levels were studied in 3,532 patients with Surgically treated gastric cancer in 52 institutions from 1980 to 1981. These patients had disease resectable with curative intent and were followed for a minimum of 5 years or until death. Among 2,749 Stage I cases, 33 had recurrence and proved to be histologically stage I. A pair matching case control study between these 33 cases and matched 33 stage I controls without recurrence proved that the preoperative CEA level was relatively higher in cases with recurrence (p = 0.079). In Stage II and III cases, an analysis of variance using a cut off level as a block factor was performed. Among 315 Stage II cases, preoperative CEA levels were significantly higher in cases with recurrence than in cases without recurrence. In 468 Stage III cases, no correlations between preoperative CEA levels and high risks of cancer recurrence were detected. In Stage I and Stage II cases, CEA levels significantly increased at the time of recurrence. In conclusion, preoperative high serum CEA levels might be considered one of the risk factors for recurrence of Stage I and II gastric cancers, and monitoring the postoperative CEA levels might be useful in early detection of recurrence.
Analysis of Variance↗
Nude mouse resists hepatic metastasis of the allogeneic tumor, colon-26.
The ability of the host-immune defense mechanism of nude mice and their immunocompetent littermates to prevent liver metastases from the murine colon carcinoma, colon-26, was assessed. Give thousand tumor cells suspended in 0.05 ml of Hank's balanced salt solution were inoculated into the spleens of BALB/c nu/+ and BALB/c nu/nu mice. On the 21st day after inoculation, all the mice were sacrificed, and the liver metastases counted and the livers weighed. All the BALB/c nu/+ mice were found to have developed hepatic metastases with a mean of 10 nodules, whereas no hepatic metastases were observed in any of the 10 BALB/c nude mice. On the other hand, 4 of 6 nude mice developed hepatic metastases after treatment with anti-asialo GM1 antibody. These results indicate that the BALB/c nude mouse has an excellent host-immune defense mechanism for preventing liver metastasis, with NK cells in the liver and/or blood circulation perhaps playing an important role.
Animals↗
[Preoperative oral antimicrobial bowel preparations in elective colorectal surgery].
Colorectal surgery is associated with high incidence of postoperative wound infection due to contamination of the field of operation by organisms from the intestine. A consecutive series of 300 patients undergoing elective operations on the colon and rectum, was studied to determine the efficacy of oral antibacterial preparations on the influence of intestinal organisms at operation and the incidence of postoperative wound infection. The patients were divided into four groups as their preoperative bowel preparations as follows; 1st group: mechanical preparation alone, 2nd group: mechanical preparation and oral kanamycin, 3rd group: mechanical preparation and oral kanamycin and metronidazole, and 4th group: mechanical preparation and oral polymyxin B and metronidazole. The results of bacteriological studies on specimens taken by swab from colonic lumen and wound at operation showed effectiveness of kanamycin and polymyxin B against aerobic gram-negative rods and metronidazole against anaerobes. The rates of postoperative wound infection were 47.5% in 1st group, 27% in 2nd group, 12% 3rd group, and 2.7% in 4th group, respectively.
Administration, Oral↗
[A case of Crohn's colitis with cecal perforation and abnormalities of coagulation and fibrinolytic system].
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Blood Coagulation↗
Conformational epitopes specific to carcinoembryonic antigen defined by monoclonal antibodies raised against colon cancer xenografts.
Four monoclonal antibodies (MoAbs) reactive with carcinoembryonic antigen (CEA) were obtained by hybridizing mouse myeloma cells (P3-X63-Ag8-U1) with spleen cells from nude mice (BALB/c, nu/nu) that had rejected transplanted human colonic adenocarcinomas Co-3 and Co-4 following intraperitoneal injection of spleen cells from immunocompetent mice (BALB/c). By solid-phase RIA with purified CEA and its related antigens, NCC-CO-413 (IgG2a, kappa) was shown to react with NCA and BGP-I as well as with CEA, whereas the reactivities of three other MoAbs, NCC-CO-308 (IgG1, kappa), -432 (IgG1 lambda), and -411 (IgG1, kappa) were limited to CEA. Immunohistochemical reactivities of these MoAbs to colonic carcinomas, granulocytes, and liver bile canaliculi on acetone-fixed paraffin-embedded sections ("AMeX" sections) confirmed the specificities of these MoAbs shown by the solid-phase RIA. By competition solid-phase RIA, the epitopes recognized by NCC-CO-308 and -432 were shown to be shared or located close to each other, whereas the other MoAbs were shown to recognize different epitopes. Thus, two epitopes specific to CEA and one shared by NCA and BGP-I as well as CEA were identified. Furthermore, reactivities of MoAbs with the two CEA-specific epitopes were easily abolished by heat denaturation or reduction of CEA, as revealed by solid-phase RIA and SDS-PAGE-immunoblotting, indicating that these two CEA-specific epitopes are based on the conformational structure of the CEA molecule.
Animals↗
Detection of increased fecal carcinoembryonic antigen and its characterization as a membrane-bound form in colorectal carcinoma and other gastrointestinal disorders.
The levels and character of carcinoembryonic antigen (CEA) in feces were investigated by sandwich radioimmunometric assay using anti-CEA monoclonal antibodies NCC-CO-411 and NCC-CO-432. Mean CEA concentration was significantly higher (P less than 0.001) in the feces from patients with colorectal carcinoma and other gastrointestinal disorders as compared to normal adults. More than 90% of the fecal CEA was trapped by a 0.22 micron membrane filter and solubilized by treatment with 1% Triton X-100 or phosphatidyl-inositol specific phospholipase C. In hydrophobic chromatography, most of the fecal CEA was eluted at the lowest (NH4)2SO4 concentration while serum CEA appeared in the more hydrophilic fractions. These results suggest that the majority of CEA exists in feces as an amphiphilic molecule or a membrane-bound form. The increase of fecal CEA may reflect the destruction and abrasion of epithelial cells in various gastrointestinal disorders.
Antibodies, Monoclonal↗
[Cooperative study of surgical adjuvant chemotherapy of colorectal carcinoma (second study): a preliminary report. Cooperative Study Group of Surgical Adjuvant Chemotherapy of Colorectal Cancer in Japan].
In a prospectively randomized study, the effect of adjuvant chemotherapy with mitomycin C (MMC) and tegafur (FT) on survival and recurrence was analyzed in 2,477 evaluable patients with colon or rectal cancer who underwent macroscopically curative resection. Patients (1,256 with colon cancer, 1,221 with rectal cancer) were divided into the treatment group (group A) and the control group (surgical resection only, group B). In group A, chemotherapy consisted of intravenous administration of MMC (12 mg/m2 on operative day, followed by 6 mg/m2/2 months, 6 times) and oral administration of FT (800 mg/day for one year). No serious adverse effects were observed in the treatment group. There was no significant difference between group A and group B in three-year survival rate. The disease-free interval curve in group A of rectal cancer revealed significantly better results than group B (p = 0.044). There was no difference in the incidence of local recurrence at three years after operation between group A and group B. The incidence of metachronous liver metastases in group A of rectal cancer was significantly lower than in group B (p = 0.036).
Antineoplastic Combined Chemotherapy Protocols↗
Antitumor activity of 7-N-(2-((2-(gamma-L-glutamylamino) ethyl) dithio) ethyl) mitomycin C (KW2149) against human tumor xenografts serially transplanted into nude mice.
The antitumor activity and toxicity of 7-N-(2-((2-(gamma-L-glutamylamino) ethyl) dithio) ethyl) mitomycin C (KW2149) were evaluated using a human tumor xenograft--nude mouse system, and compared with those of the maternal compound, mitomycin C. The maximum tolerated dose of KW2149 was estimated to be 15 mg/kg by bolus intraperitoneal or intravenous injection, at which a remarkable reduction of spleen weight was observed, suggesting bone marrow suppression by this agent. A bolus injection of KW2149 seemed to be more effective than a divided injection schedule, when a total of 15 mg KW2149/kg was administered to mice bearing breast (MX-1) and colon (Co-4) carcinomas. The antitumor activity of KW2149 was dose-dependent, and the difference in antitumor effect according to route of administration was minimal. The antitumor spectrum of KW2149 was essentially identical to that of mitomycin C administered intraperiotoneally as a bolus at a dose of 6 mg/kg.
Adenocarcinoma↗
[The influence of theophylline on polyamine metabolism and colonic carcinogenesis induced by 1.2-dimethylhydrazine in mice].
The administration of theophylline (120 mg/kg.day, 14 wk) to the drinking water of female BALB/c mice after treatment with 1,2-dimethylhydrazine (DMH) (30 mg/kg.sc, 1/wk, 14 wk) resulted in both an increase in number of colon carcinoma and increases in ornithine decarboxylase (ODC) activities and polyamine (PA) levels in colon tissue. This increase in number of colon carcinoma was about 3-fold to mice receiving same amount of DMH and drinking water without theophylline. ODC activities (pmoles 14CO2/hr/mg prot, mean +/- SD) in colon tissue were 122 +/- 10.6 (n = 6) in DMH with theophylline group, 28.3 +/- 2.13 (n = 8) in DMH alone group, 21.3 +/- 1.67 (n = 6) in control group respectively. Putrescine and spermidine levels (nmoles/g, mean +/- SD) were 31.0 +/- 10.5, 527 +/- 86.6 (n = 11) in DMH with theophylline group, 24.0 +/- 11.4, 464 +/- 129 (n = 11) in control group respectively. Thus with marked increase of ODC activities and slight increase of PA levels, theophylline has shown to significantly enhance the promoting phase of carcinogenic process with DMH.
Animals↗
[Phase II study with cisplatin in advanced stomach and colon carcinoma. Cooperative Study Group of Cisplatin for Stomach and Colon Carcinoma].
A multicenter phase II study was performed to evaluate cisplatin (CDDP) in patients with gastric carcinoma or colon carcinoma. Ninety-nine cases of gastric carcinoma and 25 cases of colon carcinoma were entered into the study. According to the eligibility criteria prepared for the study protocol, 28 and 5 patients were excluded from the stomach and colon group, respectively. CDDP, 70-100 mg/m2, was administered intravenously with sufficient hydration. The efficacy rates evaluated by the UICC tumor reduction criteria were 19.1% (13/68 cases) in gastric carcinoma and 5.0% (1/20 cases) in colon carcinoma. Lymph node metastasis and metastatic abdominal tumor were effective targets for CDDP treatment. As side-effects of CDDP, nausea/vomiting (69.2%) and general malaise (35.2%) were observed. CDDP was thus considered to be one of the effective chemotherapeutic agents for treatment of gastric carcinoma.
Adult↗
[Hepatic arterial infusion chemotherapy using totally implantable reservoir in liver metastases in colorectal cancer].
Hepatic arterial infusion chemotherapy using totally implantable reservoir was performed for the treatment of liver metastases of colo-rectal cancers, and the therapeutic effects, side effects and complications were evaluated. Reservoir catheters were implanted into hepatic artery via gastroduodenal artery during operation. Mitomycin C (MMC), adriamycin (ADM), and 5-fluorouracil (5-FU) were used as chemotherapeutic agents. Eleven cases of H1 (metastases in one lobe only), 7 cases of H2 (a few scattered metastases in both lobes) and 12 cases of H3 (multiple metastases in both lobes) were treated intermittently with one-shot administration of MMC or ADM (A-group). Ten cases (H1: 1, H2: 2, H3: 7) were treated with intermittent one-shot administration of MMC or ADM following two-week continuous infusion of 5-FU through infusion pump after operation (B-group). In 5 of 10 cases of B-group, serum CEA level fell below the preoperative level, and the tumor size regressed in 3 of those 5 cases which were evaluated on the basis of CT scan. But no remarkable change in CEA level or tumor size on CT scan was seen in A-group. No particular side effect such as leucopenia, liver dysfunction or gastroduodenal symptom was noted except one case developing multiple gastric ulcers and pancreatitis in B-group. Five cases (25%) showed obstruction of catheter and 3 cases (14%) evidence leakage of chemotherapeutic agents in A-group. Three cases (30%) in agents in A-group. Three cases (30%) in B-group displayed obstruction of gastroduodenal artery beyond the tip of catheter. Median survival time of both groups (A, B) was 6 months and 12 months, respectively. The treatment seemed effective for the improvement of serum CEA level and tumor size, and there was a tendency toward prolongation of survival time in B-group.
Adult↗
[Clinical evaluation of serum level of NCC-ST-439 as a new tumor marker for colorectal diseases--fluctuation of serum NCC-ST-439 in patients with colorectal cancers before and after surgery].
Serum level of NCC-ST-439, a new tumor marker, was clinically evaluated in patients with benign and malignant colorectal diseases in comparison with serum CEA and CA 19-9. Fluctuation of serum levels of NCC-ST-439 in patients with colorectal cancers was especially studied. Serum level of NCC-ST-439 was determined by sandwich type NCC-ST-439 EIA kit, which was developed by Nippon Kayaku Co., Ltd., in 93 cases of primary colorectal cancers, 98 cases of recurrent colorectal cancers and 60 cases of benign colorectal diseases. Positive rate of serum NCC-ST-439 in patients with primary colorectal cancers was 8.6% in Dukes A cases, 14.3% in Dukes B cases, 37.5% in Dukes C cases and 78.9% in Dukes D cases. Positive rate in patients with recurrent colorectal cancers was 42.8%. On the other hand, false positive rate in patients with benign colorectal diseases was 5.0%, which was relatively low in comparison with serum CEA and CA 19-9. While serum NCC-ST-439 was well correlated with serum CEA and CA 19-9 in primary colorectal cancers, NCC-ST-439 value in benign colorectal diseases showed no correlation with serum CEA and CA 19-9. In patients with primary colorectal cancers, curative resection was applied for in 40 cases in which the value recovered to the normal range after resection. In contrast, all 8 cases, which received non-curative resection, showed the increase of serum NCC-ST-439 value. In cases of recurrent colorectal cancers, some cases, which responded against chemotherapy, obviously showed a decrease of NCC-ST-439 value. These facts indicated that serum level of NCC-ST-439 could monitor the clinical effects of surgical treatment, chemotherapy and radiation therapies and it could be used as a marker for colorectal cancers. In conclusion, determination of serum NCC-ST-439 value was clinically useful for the diagnosis and monitoring for patients with colorectal cancers as a new distinct tumor marker.
Antigens, Tumor-Associated, Carbohydrate↗
Selection of a monoclonal antibody reactive with a high-molecular-weight glycoprotein circulating in the body fluid of gastrointestinal cancer patients.
The monoclonal antibody NCC-CO-450 (IgM kappa) was selected by screening of reactivity with high-molecular-weight antigens (Mr greater than 10(6] isolated from ascitic fluid of a colon cancer patient. This antibody detected heterogeneous but predominantly high-molecular-weight antigens in 4 of 6 ascitic fluid samples from gastrointestinal cancer patients by immunoblotting analysis. A sandwich radioimmunoassay was developed in order to examine the serum level of this antigen, and the cutoff value was defined as the mean plus 2 SD of values obtained with sera from normal donors. While 97% (93 of 96) of sera had a negative antigen value in normal donors, 56% (14 of 25) of patients with colorectal carcinoma and 40% (8 of 20) of patients with gastric carcinoma showed a positive antigen value. The distribution of the antigen in sera of patients with various cancers did not show any correlation with the distribution of carcinoembryonic antigen or CA 19-9. From immunohistochemical and biochemical analyses, NCC-CO-450 antigen was characterized as a mucin-like glycoprotein abundant in normal colonic epithelium as well as in carcinomas of the colon, stomach, and pancreas. The immunohistochemical reactivity of NCC-CO-450 was distinct from that of other monoclonal antibodies reported to be useful for serological diagnosis. The epitope recognized by NCC-CO-450 is considered to be an O-linked carbohydrate chain without terminal sialic acid but is different from the known carbohydrate chains, i.e., Lea, Lex, LeY, Tn, sialyl-Lea, and sialyl sugar chain defined by NCC-ST-439 in a competitive binding inhibition assay of monoclonal antibodies. This newly defined antigen is a good example of a normal antigen shed from cancer cells that can be used successfully as a serum tumor marker.
Animals↗
Sandwich radioimmunometric assay with murine monoclonal antibody, NCC-ST-439, for serological diagnosis of human cancers.
Sandwich radioimmunometric assay (RIA) for a new tumor-associated carbohydrate antigen defined by a monoclonal antibody (MoAb), NCC-ST-439, was developed and the antigen levels were determined in sera of normal donors, and patients with various malignant and non-malignant disorders. In normal donors, 97.0% (226/233) of sera were antigen-negative (less than 12 units/ml) except for 7 serum samples from young females. In patients with malignant disorders, 34.2% (82/240) were antigen-positive, in particular 64.0% (16/25) of patients with pancreatic carcinoma, 66.7% (16/24) of patients with recurrent colorectal carcinoma and 54.5% (6/11) of patients with recurrent breast carcinoma. In patients with non-malignant disorders, 6.0% (7/116) were antigen-positive. The positive rate in benign hepatobiliary disorders, including gallstones, hepatitis and liver cirrhosis, was especially low at 4.3% (1/23). We concluded that determination of serum NCC-ST-439 antigen would be useful in serodiagnosis of carcinoma patients.
Adult↗
[Transcatheter arterial chemoembolization and selective hepatic arterial infusion using totally implantable reservoir].
Transcatheter arterial chemoembolization (TAE) and hepatic arterial infusion using totally implantable reservoir were performed for the treatment of liver metastasis of colo-rectal cancers, and their therapeutic effects, side effects and complications were evaluated. Eleven cases of H1 (metastasis in one lobe only), 7 cases of H2 (a few scattered metastases in both lobes), 12 cases of H3 (numerous metastases in both lobes) were entered into the study and underwent TAE 45 times. Gel foam, Ivaron and Lipiodol were used as embolic materials in combination with chemotherapeutic agents such as mitomycin C and adriamycin. Serum CEA level was decreased less than 50% of pre-TAE level 20 out of 32 (61%). The tumor size was regressed in 25% of TAE cases which were evaluated on the basis of CT scan. Abdominal symptoms including abdominal pain, nausea and vomiting and fever, leukocytosis, elevated GOT, LDH and bilirubin level were seen after TAE therapy. Median survival of H1, H2 and H3 cases were 21 months, 8 months and 4.5 months, respectively. Another 21 cases (H1, 5 cases: H2, 3 cases: H3, 13 cases) of liver metastasis of colo-rectal cancers were treated with selective hepatic arterial infusion therapy using totally implantable reservoir. Reservoir catheters were implanted into hepatic artery via gastroduodenal artery under direct vision at laparotomy. Mitomycin C, adriamycin and fluorouracil (5-FU) were used as chemotherapeutic agents. No particular side effect such as leukopenia or liver dysfunction was noted. Median survival of H1, H2 and H3 cases treated with arterial infusion were 4 months, 9 months and 9 months, respectively. Median survival of TAE cases and arterial infusion cases was 10 and 6 months, respectively. Thus, the survival rate of cases treated with TAE was better than that of cases treated with arterial infusion.
Antineoplastic Combined Chemotherapy Protocols↗
Two cases of rectal carcinoma associating aorto-iliac occlusive disease.
Two cases of rectal carcinoma associating aorto-iliac occlusive disease are presented. These two cases had complete obstruction of the affected vessels, but many collateral pathways from the aorta to the legs had developed, mainly through the superior rectal artery or parietal vessels. Changes in blood flow to the legs, following the radical operation for rectal carcinoma, were examined by both preoperative angiography and perioperative Doppler flow meter. Vascular reconstruction was carried out in one case prior to resection of the rectum, in order to prevent the ischemic legs from becoming worse, or necrotic. The indications for supportive vascular surgery in the case of rectal carcinoma with aorto-iliac occlusive disease are discussed herein.
Adenocarcinoma↗