Inhibitory Effects of Ginsenoside Rh2 on Tumor Growth in Nude Mice Bearing Human Ovarian Cancer Cells

Ginsenoside Rh₂ (Rh₂), isolated from an ethanol extract of the processed root of Panax ginseng CA Meyer, inhibits the growth of B16 melanoma cells. This study was designed to evaluate the ability of Rh₂ to inhibit growth of human ovarian cancer cells (HRA) in vitro and in nude mouse. Rh₂ inhibited proliferations of various established human ovarian cancer cell lines in a dose-dependent manner between 10 and 60 μM in vitro and induced apoptosis at around the IC₅₀ dose. When HRA cells were inoculated s.c. into the right flank of nude mice, all mice formed a palpable tumor within 14 days. Although i.p. administration of Rh₂ alone hardly inhibited the tumor growth, when Rh₂ was combined with cis-diamminedichloroplatinum(II) (CDDP) the tumor growth was significantly inhibited, compared to treatment with CDDP alone. When mice were treated p.o. with Rh₂ daily (but not weekly), the tumor growth was significantly (P<0.01) inhibited, compared to CDDP treatment alone. When Rh₂ was combined with CDDP, the degree of tumor growth retardation was not potentiated. The survival time was significantly (P<, we examined whether p.o. administration of Rh₂ has a dose-dependent inhibitory effect on the tumor growth. I.p. and weekly administration of CDDP had more potent antitumor activity in the order of 1 mg/kg, 2 mg/kg and 4 mg/kg, whereas p.o. and daily administration of Rh₂ (0.4 to 1.6 mg/kg) not only had antitumor activity comparable to that of 4 mg/kg CDDP, but also resulted in a significant increase of the survival. Doses of Rh₂ used in this study did not result in any adverse side-effects as confirmed by monitoring hematocrit values and body weight, unlike 4 mg/kg CDDP, which had severe side-effects. It is noteworthy that p.o. but not i.p. treatment with Rh₂ resulted in induction of apoptotic cells in the tumor in addition to augmentation of the natural killer activity in spleen cells from tumor-bearing nude mice. Thus, particularly in view of the toxicity of CDDP, Rh₂ alone would seem to warrant further evaluation for treatment of recurrent or refractory ovarian tumor.     

Inhibition of thromboxane production might ameliorate liver blood flow in shock

We investigated whether thromboxane (TX), a vasoconstrictor, contributes to liver disturbance in shock by reducing liver blood flow. Subjects and methods: experimental groups: Sham, Et: endotoxin 4mg/kg, BDL + Et: bile duct ligation with Et, OKY. BDL + BDL + Et with infusion of OKYO46 (TX synthetase inhibitor) 5mg, HT: three days after 70% hepatectomy, OKY. HT: HT receiving OKYO46. We evaluated prostanoid and morbidity in hepatectomized cases. Measurement: TX, liver phospholipid, liver blood flow, endotoxin. Results: Higher TX levels in blood and liver, and reduced liver phospholipid and liver blood flow in BDL + Et returned close to sham by OKYO46. High blood endotoxin in HT decreased by OKYO46. Intraoperative blood losses in cases with postoperative intraabdominal infection or hepatic failure were greater than those without complication. Hepatectomized cases with intraabdominal infection showed higher blood TX than those without complication. TX might be associated with decreased liver blood flow and with postoperative complication during shock. To reduce TX production would be beneficial in shock by ameliorating liver blood flow.     

Distribution of a squamous cell lung carcinoma-associated antigen, KA-32, in human tissues and sera defined by monoclonal antibody KM-32

The distribution of a variant of blood group A antigen recognized by a murine monoclonal antibody, KM-32, generated against human squamous cell lung carcinoma was investigated in various tissues and sera. By immunoperoxidase staining, the antibody was found to react with a number of lung carcinoma tissues of squamous cell carcinoma, adenocarcinoma, and small cell carcinoma, and several other tumor tissues. Positive staining was also observed in a small number of cells of some normal tissues, such as bronchiolar epithelium, gastrointestinal glands, and convoluted tubules of the kidney. The antibody could also be used in detecting macromolecular antigens, designated KA-32, in sera of patients with lung cancer. The antigen level in serum was determined by an inhibition assay using purified KM-32. The higher level of inhibition was seen in sera from over half of patients with lung cancer and patients with benign diseases when compared with those in sera from healthy adults. Purification of the antigen in serum was performed by gel filtration chromatography, immunoaffinity chromatography, and polyacrylamide gradient gel electrophoresis. Purified antigen exhibited a glycoprotein nature, and its molecular weight was estimated at more than 500,000.     

Multi-drug resistant breast cancer responding to chemotherapy with docetaxel (taxotere: TXT)]

The patient was a fifty-five year old female who had stage IVb advanced breast cancer with hypoxia due to bilateral pulmonary metastases and lymphangitis. The cancer was adriamycin (ADM) and multi-drug resistant. We administered docetaxel (taxotere: TXT) 60 mg/m2 every 3 weeks. After 2 courses, the pulmonary metastases had become remarkably reduced in size and hypoxia was reduced and performance status (PS) improved. Major toxic defects were grade-4 neutropenia and hair loss. The patient could be discharged from the hospital without O2 inhalation and enjoyed a better quality of life (QOL). This chemotherapy is thought to be effective against ADM and multi-drug resistant breast cancer.     

Analysis of risk factors for recurrence and effective adjuvant therapy in patients with endometrial cancer

Objective: The aim of this study was to explore risk factors for recurrence and effective adjuvant therapy in endometrial cancer.

Methods:

Methods: Between 1985 and 1999, 170 patients with uterine endometrial cancer received initial therapy at the National Defense Medical College Hospital. We retrospectively analyzed risk factors including; histopathological features, operative procedures, adjuvant therapies and surgical staging.

Results:

Results: Although the prognosis in stage I and II patients was fairly good, recurrences were observed in patients with stage Ib or worse. Vagina walls were the frequent site of recurrence. About a half of relapses which occurred within seven months after surgery were observed during adjuvant chemotherapy. Multivariate analysis revealed that myometrial invasion ( P = 0.0231) was the only risk factor for recurrence. Although the prognosis in stage III and IV patients was generally poor, serosal invasion in stage III disease seemed to be an im-portant risk factor. With regard to adjuvant therapy in stage I–III patients who could receive optimal cytoreductive surgery; the risk of recurrence was significantly ( P = 0.0127) lower in patients receiving radiation therapy than in those receiving chemotherapy including platinum agents.

Conclusion:

Conclusion: The data suggested that in stage I–III patients with optimal cytoreductive surgery, myometrial invasion is an independent risk factor for recurrence and radiation therapy is more effective than chemotherapy as adjuvant therapy.     

Optimal Propofol Plasma Concentration during Upper Gastrointestinal Endoscopy in Young, Middle-aged, and Elderly Patients

Background: Suitable propofol plasma concentrations during gastroscopy have not been determined for suppressing somatic and hemodynamic responses in different age groups.

Methods: Propofol sedation at target plasma concentrations from 0.5 to 4.0 [mu]g/ml were performed randomly in three groups of patients (23 per group) who were undergoing elective outpatient gastroscopy: ages 17-49 yr (group 1), 50-69 yr (group 2), and 70-89 yr (group 3). Plasma propofol concentration in which 50% of patients do not respond to these different stimuli were determined by logistic regression: verbal command (Cp50ls), somatic response to gastroscopy (Cp50endo), and gag response to gastroscopy (Cp50gag). Hemodynamic responses were also investigated in the different age groups.

Results: Cp50ls concentrations were 2.23 [mu]g/ml (group 1), 1.75 [mu]g/ml (group 2), and 1.40 [mu]g/ml (group 3). The Cp50endo values in groups 1 and 2 were 2.87 and 2.34 [mu]g/ml, respectively, which were significantly higher than their respective Cp50ls values. Cp50endo value in group 3 was 1.64 [mu]g/ml, which was close to its Cp50ls value. Because of a high degree of interpatient variability, Cp50gag could not be defined. Systolic blood pressure response decreased with increasing propofol concentrations.     

Enhanced tumor cell selectivity of adriamycin-monoclonal antibody conjugate via a poly(ethylene glycol)-based cleavable linker.

A novel linker consisting of poly(ethylene glycol) (PEG) and dipeptide was used for conjugation of adriamycin with tumor-specific monoclonal antibody, NL-1, to confirm that the linker can be cleaved selectively with the tumor specific enzyme to express cytotoxicity of the anti-tumor agent. Initially, adriamycin-conjugated PEG linkers through different amino acid compositions, alanyl-valine (Ala-Val), alanyl-proline (Ala-Pro), and glycyl-proline (Gly-Pro) sequences, were prepared to confirm selective digestion with model enzymes. Adriamycin was released by particular model endoproteases, thermolysin and proline endopeptidase, from the linkers with different efficiency. When conjugates were prepared using these adriamycin-bound linkers, conjugates had no loss of binding affinity and specificity for common acute lymphoblastic leukemia antigen (CALLA) expressed on the Daudi cell surfaces as the target of NL-1 antibody. In addition, adriamycin release from the conjugates was also confirmed by incubating them with specific proteases. Tumor cell growth was inhibited dose-dependently for the conjugates carrying Ala-Val and Gly-Pro linkers, whereas significant inhibitory effect was abolished for the conjugate carrying Ala-Pro linker, indicating that cytotoxic effect can be controlled by specificity of antibody and composition of linker peptide. IC(50) for Ala-Val linked conjugate was approximately 3.5 microg/ml and that for Gly-Pro linked conjugate was 5.2 microg/ml. PEG-dipeptidyl linker demonstrated here will be an effective tool for the preparation of immunoconjugate, especially specific activation of anti-tumor agents at desired tumor tissues.     

The role of serum KL-6 measurement in common pediatric respiratory infections

KL-6 is a useful marker for interstitial pneumonia of various origins. However, the role of KL-6 in common pediatric respiratory infections is largely unknown. In order to determine whether the KL-6 level is elevated during respiratory infection, and whether KL-6 is a useful biomarker for the disease activity, we evaluated serum KL-6 levels in 132 children with various respiratory infections. KL-6 levels were significantly higher in patients with measles, influenza, or respiratory syncytial virus infection than in the control subjects. On the other hand, KL-6 levels in patients with bacterial infections such as mycoplasma, chlamydia, or pertussis were comparable to the control values. In patients with viral infections, high KL-6 levels, as defined by the mean plus 2 standard deviations of the control group, significantly correlated with low SpO₂ or days of O₂ administration, but did not correlate with C-reactive protein or white blood cell counts. These results indicate that measurement of serum KL-6 levels is helpful for the management of common pediatric respiratory infections.     

Neutrophil alkaline phosphatase activity in respiratory viral infection

Neutrophil alkaline phosphatase (NAP) is used as a diagnostic marker in several hematological disorders. In regard to the role of NAP in infectious diseases, previous investigators have presented the hypothesis that NAP activity is useful to distinguish viral infections from bacterial infections. Because the numbers of patients enrolled in previous studies of viral infections were limited, we intended to evaluate the hypothesis by measuring NAP activity in a large number of pediatric patients with respiratory viral infections. A cytochemical analysis of NAP was performed in 160 patients with various types of respiratory infections. In patients with adenovirus or respiratory syncytial (RS) virus infection, NAP activity was significantly higher than the control value newly established at our department, while in patients with Epstein-Barr virus, measles, or influenza infection, it was comparable to the control value. On an individual basis, NAP scores (determined from NAP cytochemical activity) in 22 of 26 patients (84.6%) with adenovirus infection, and 31 of 42 patients (73.8%) with RS virus infection were found to exceed the 95% confidence upper limit of the control group. In conclusion, NAP activity is quite varied among different respiratory viral infections. When NAP activity is high in respiratory infections, adenovirus or RS virus infection, as well as bacterial infections, should be taken into consideration.     

Therapeutic leukocytapheresis for inflammatory bowel disease.

The inference that granulocytes and monocytes/macrophages (GM) are part of the immunopathogenesis of inflammatory bowel disease (IBD) and hence should be targets of therapy stems from observations of elevated, and activated GM in patients with IBD. The Adacolumn can selectively deplete GM by adsorption (GMA) and in patients with IBD, GMA has been associated with significant clinical efficacy together with sustained suppression of inflammatory cytokine profiles. Additionally, GMA depleted proinflammatory CD14(+)CD16(+) monocytes and was followed by an increase in CD4(+) T lymphocytes including the regulatory CD4(+)CD25(high+)Foxp3 phenotype. Hence, GMA could be a non-pharmacologic therapy for IBD with potential to spare steroids and other unsafe pharmacologic preparations.