Simultaneous determination of glycyrrhizin and liquiritin in licorice roots and Kampo medicines by combination enzyme-linked immunosorbent assay using anti-glycyrrhizin and anti-liquiritin monoclonal antibodies

Immunoassay systems using monoclonal antibodies (mAbs) are one of the most useful techniques in the analytical, biochemical, and clinical fields. In this study, a combination enzyme-linked immunosorbent assay (ELISA) using both anti-glycyrrhizin and anti-liquiritin mAbs (anti-GL/Liq mixture mAbs) was developed for quality control of licorice and its products. The combination ELISA demonstrated high sensitivity, reproducibility, and specificity for the total content of GL and Liq by a single assay. The developed ELISA was effective and useful as the first screening method in the selection of high-quality licorice from the Glycyrrhiza species and in confirming the quality of licorice-containing Kampo medicines.     

Potentiation of antitumor and antimetastatic activities of adriamycin by a novel N-alkylated dihydropyridine,AC394, and its enantiomers in colon cancer-bearing mice

 Purpose: We have previously shown that a series of N-alkylated 1,4-dihydropyridines potentiate the therapeutic efficacy of vincristine in vincristine-resistant P388 leukemia. The purpose of this study was to investigate the ability of one of the compounds, AC394, and its enantiomers to potentiate the antitumor activity of adriamycin against colon cancer cells in vitro and in vivo. Methods: The effects of AC394 on potentiation of adriamycin cytotoxicity and enhancement of its accumulation were evaluated using colon 26, HCT-15 and MCF-7 cells. Furthermore, the activities of AC394 and its enantiomers were compared. We also studied the combined effects of (+)-AC394 and adriamycin on subcutaneously (s.c.)-implanted and liver metastasis tumor models. Results: AC394 potentiated the cytotoxicity of adriamycin and enhanced its accumulation in colon cancer cells (colon 26 and HCT-15), which are known to express P-GP (P-glycoprotein) intrinsically. Enhancement of adriamycin accumulation by AC394 was found in s.c.-implanted colon 26 cells in vivo. Although both enantiomers of AC394 showed equal activity in vitro, (+)-AC394 was more effective than (−)-AC394 given orally. (−)-AC394 was found to be cleared more rapidly from the plasma than (+)-AC394. Thus, (+)-AC394 was evaluated for further study. Administration of (+)-AC394 significantly potentiated the antitumor activities of adriamycin in human colon cancer HCT-15 cells implanted s.c. Furthermore, in the liver metastasis model using colon 26 cells, a model completely resistant to adriamycin, the combination therapy of adriamycin with (+)-AC394 produced superior antitumor effects over adriamycin alone. Conclusions: A newly synthesized N-alkylated 1,4-dihydropyridine derivative, (+)-AC394, showed superior effects on the potentiation of adriamycin antitumor and antimetastatic activities in vivo. These results suggest that this combination may have therapeutic efficacy not only against primary colon cancers but also against metastatic liver cancer. Received: 19 June 1995/accepted: 6 December 1995     

Primary Hepatocellular Carcinoma and Hepatoid Adenocarcinoma of the Stomach with Liver Metastasis: An Unusual Association

Alpha-fetoprotein (AFP)-producing hepatoid adenocarcinoma ofthe stomach is a rare and recently discovered entity. We reportan unusual combination of hepatocellular carcinoma and hepatoidadenocarcinoma of the stomach with multiple liver metastases.The patient, a 62-year-old Japanese man, was clinically diagnosedas having hepatocellular carcinoma because of the presence ofliver tumors, a markedly elevated serum AFP level, and a positivehepatitis C virus (HCV) antibody titer. Autopsy revealed multipletumors in the liver; one was a primary hepatocellular carcinomawithout metastasis, and the others were metastases from latenthepatoid adenocarcinoma of the stomach. In the hepatocellularcarcinoma, bile production was observed although the tumor wasimmunohistochemically negative for AFP. On the other hand, boththe primary gastric and metastatic liver hepatoid adenocarcinomaswere positive for AFP. Therefore, hepatoid adenocarcinoma ofthe stomach was responsible for the excessive production ofAFP and was the cause of death.     

Tissue reactions after intraosseous implantation of three retrofilling materials

Bone tissue reactions to EBA, IRM, and cyanoacrylate cement (Base Liner) were studied in the rat mandible using an intraosseous implant method. Osseous cavities (1.4 mm in diameter) were surgically created in the mandibles, and materials were implanted in 60 male Wistar rats. Each specimen was evaluated histologically after 4 and 8 weeks. The development of fibrous connective tissue in direct apposition to the material was observed in the EBA and IRM groups at 4 weeks. A slight degree of macrophage infiltration was seen in the EBA group. After the 8-week observation period, IRM and EBA were frequently separated from the bone cavity by a fibrous connective tissue layer (p < 0.01). The Base Liner appeared to be in direct apposition to the osseous tissue in several areas (p < 0.01). These findings indicate that Base Liner reacts favorably with osseous tissue, compared with the EBA and IRM materials tested and seems to be a biocompatible material.     

Recurrence of right breast cancer at the thoracic wall successfully treated with intra-arterial infusion of doxorubicin hydrochloride--a case report

We report a recurrent case of breast cancer successfully treated with intra-arterial infusion of doxorubicin hydrochloride (ADM) combined with systemic CAF therapy. The patient, a 37-year-old woman, was diagnosed with a recurrence at the thoracic wall 55 months after curative resection for right breast cancer. She was treated with intra-arterial infusion chemotherapy of ADM, 30 mg, combined with systemic CAF therapy of cyclophosphamide, 100 mg from days 1 to 14, ADM, 30 mg on days 1 and 8, and 5-fluorouracil, 500 mg on days 1 and 8, as one course. Two courses of the treatment resulted in a complete response of the tumor. This result suggests that local and systemic chemotherapy could be effective for the treatment of local recurrence of breast cancer.     

Multicentric infantile myofibromatosis with spontaneous regression

We report a patient with multicentric infantile myofibromatosis who showed remarkable regression of the lesions. This 7-month-old male was admitted for evaluation of generalized subcutaneous tumor nodules. A radiographic bone survey revealed radiolucent lytic areas in the skull, axis, rib, humerus, femur, ilium, and tibia that resembled a primary neoplasm with multiple metastases. An exisional biopsy, however, led to a diagnosis of infantile myofibromatosis. All the subcutaneous nodules regressed spontaneously within 1 year and 9 months. Correspondence to: Y. Yamaguchi     

Circulating soluble Fas ligand in patients with gastric carcinoma

BACKGROUND: The Fas/Fas ligand (FasL) system is involved in cancer cell death induced by the immune system. Most of the tumors may escape the host immune attack by imitating themselves as immune-privileged sites by overexpressing FasL. FasL is synthesized as a membrane-bound protein that can be cleaved to the soluble isoform (sFasL). The objectives of this work were to determine whether the serum concentrations of sFasL in patients with gastric carcinoma were correlated with clinicopathologic features and survival rates. METHODS: The authors examined the circulating sFasL concentration in 43 healthy people and 166 primary gastric carcinoma patients at the time of diagnosis by enzyme linked immunoadsorbent assay. The results were categorized by clinical and histopathologic variables. RESULTS: The serum sFasL levels of healthy subjects were all less than 0.1 ng/mL. Among the 166 gastric carcinoma patients, the median concentration of sFasL was 0.04 ng/mL. There were no significant differences between the healthy controls and the gastric carcinoma patients group (P = 0.738). The sFasL levels were significantly increased in patients with gastric carcinoma in a manner reflective of the disease stages such as the depth of tumor invasion, lymph node metastasis, and distant metastasis. The authors determined the cutoff value (0.08 ng/mL) as a 90th percentile of healthy controls. The survival analysis demonstrated that patients with high sFasL levels had a worse prognosis than those with low levels (P < 0.001). Multivariable analysis confirmed that the sFasL concentration was an independent prognostic indicator of overall survival (P = 0.041). CONCLUSIONS: Our results indicated that sFasL concentrations could not be a new marker for early detection of gastric carcinoma but a prognostic tumor marker for the assessment of the progression of advanced gastric carcinoma.     

A study of plasma atrial natriuretic peptide, antidiuretic hormone and aldosterone levels in a series of patients with intracranial disease and hyponatremia]

For intracranial diseases, plasma atrial natriuretic peptide (ANP), antidiuretic hormone (ADH) and aldosterone were determined and their effects on the development of hyponatremia with central origin were studied. The subjects were 71 cases of intracranial diseases which were admitted to our hospital during a period of 1 year from March, 1989 to March, 1990. The diseases were broken down to subarachnoid hemorrhage 26 cases, hypertensive intracerebral hemorrhage 19 cases, head injury 12 cases, cerebral infarction 11 cases and 3 other cases. Serum-urine electrolytes, plasma ANP and ADH were determined in the acute stage on Day 1 to 4, in the hyponatremia stage on Day 5 to 14 and in the chronic stage on Day 15 downward. Hyponatremia was defined as the serum sodium level of 130 mEq/l or less. Cases evidently having other causes such as heart failure and renal insufficiency were excluded. In the normal control group of persons who were admitted to our hospital for a close checkup (n = 20), plasma ANP was 26.5 +/- 11.6 pg/ml (10-50); levels of 50 pg/ml or more were regarded as abnormally high. 1) Hyponatremia was found in 18 cases (25.4%), subarachnoid hemorrhage in 7 cases, hypertensive intracerebral hemorrhage in 4 cases, head injury in 5 cases and others in 2 cases. 2) The time of onset of hyponatremia was on the 8.3 hospital day. The duration was 7.2 days. The minimum serum sodium level was 124.6 mEq/l. 3) There was no significant change in the plasma aldosterone level at each stage.2+ Predicting development of hyponatremia from plasma ADH and ANP levels in the acute stage is difficult. Inadequate secretion of ANP rather than ADH appeared to be an important factor for the development of hyponatremia, but the plasma ANP level was not always abnormally high, so involvement of other sodium diuretic factors should also be kept in mind.     

Two cases of advanced gastric cancer, successfully treated with TS-1/CDDP combination chemotherapy--case report

We reported 2 cases with advanced gastric cancer, successfully treated with TS-1 and CDDP. Case 1 had Type 3 gastric cancer with left supra-clavicular (Virchow) and para-aortic lymph node metastases. Those distant node metastases completely disappeared after two courses of neoadjuvant chemotherapy (NAC) consisting of TS-1/ CDDP, and radical surgery for cure was conducted. The second case had Type 3 carcinoma with peritoneal dissemination. The primary lesion significantly decreased after four courses of the combination chemotherapy. The patient has been alive for 1 year and a half after 14 courses of TS-1/CDDP with stable disease. Significance of TS-1/CDDP in far advanced gastric cancer was discussed.     

A case report of severe laryngeal edema which occured before removal of a laryngeal mask airway

A 41-year-old woman was scheduled for a partial hip arthroplasty. She was suffering from malignant rheumatoid arthritis for a long time and we recognized her difficult airway. After epidural catheterization, anesthesia was induced with fentanyl, thiopental, and 5% sevoflurane with oxygen. A laryngeal mask airway (LMA ; size 3) was inserted smoothly on third trial after suxamethonium chloride administration. Anesthesia was maintained with fentanyl, vecuronium bromide, sevoflurane with oxygen and epidural anesthesia. No complications were observed during the operation. After reversal of muscle relaxant, spontaneous respiration returned. But inspiratory stridor and chest wall retraction occurred soon, and we found severe epiglottic edema by bronchoscopy. A tracheal tube (ID 5.5 mm) was intubated immediately through the LMA. Twenty hours later the pharyngeal edema was still very severe, and tracheotomy was performed. The edema disappeared three days later. We thought the edema had occurred as a result of blood flow disturbance caused by LMA in narrow pharyngeal space expanding to the epiglottis. It should be kept in mind that severe edema could develop after LMA in malignant rheumatoid arthritis.