RBEs of Thermal Neutron Capture Therapy and 10B(n,α)7 Li Reaction on Melanoma-Bearing Hamsters

Using Greene's melanoma transplanted into Syrian (golden) hamsters, we determined the relative biological effectiveness (RBE) of thermal neutron capture therapy (TNCT) using ¹⁰B-paraboronophenylalanine (¹⁰B-BPA) in comparison with a 9-MeV electron beam. We also obtained the RBE of the ¹⁰B(n,α)⁷Li reaction by calculation based on summed dose data from TNCT. Throughout this study, the Kyoto University Research Reactor was used as the source for thermal neutrons; the reactor was specially altered to attain a low contamination level both for gamma-rays and fast neutrons. ¹⁰B-BPA was administered 8 hours before thermal neutron irradiation to the hamsters with melanoma. The tumor was then irradiated at 5 MW for 90 minutes. The absorbed dose from this TNCT was calculated by the method of Fairchild and Goodman (Phys. Med. Biol. 1966; 2:15–30). The RBEs of the TNCT and the ¹⁰B(n,α)⁷Li reaction obtained by the tumor growth delay time (TGDT) method were 2.22 and 2.51, respectively, at 10.5 days of TGDT. These RBE values varied with TGDT and the absorbed dose. The RBE value of TNCT had a peak at 7.0 days of TGDT; that of the ¹⁰B(n,α)⁷Li reaction was higher at a low absorbed dose level and lower at a high absorbed dose level.     

IL-10 is up regulated in early and transitional stages in vervet monkeys experimentally infected with Trypanosoma brucei rhodesiense

IL-10 has been suggested as a possible parameter for human African trypanosomiasis stage determination. However, conclusive experimental studies have not been carried out to evaluate this, which is a prerequisite before a potential test can be validated in humans for diagnostic purposes. We used the vervet monkey model of trypanosomiasis to scrutinize IL-10 in blood and cerebrospinal fluid (CSF). Five adult males were experimentally infected with T. b. rhodesiense. The infected animals became anemic and exhibited weight loss. Parasitemia was patent after 3 days and fluctuated around 3.7 × 10⁷ trypanosomes/ml throughout the experimental period. The total CSF white cell counts increased from pre-infection means around 3 cells/μl to a peak of 30 cells/μl, 42 days post-infection (DPI). IL-10 was not detectable (< 2 pg/ml) in serum prior to infection. IL-10 serum concentrations increased to 273 pg/ml 10 DPI coinciding with the first peak of parasitemia. Thereafter the levels declined to a mean value of 77 pg/ml 34 DPI followed by a significant rise to a second peak of 304 pg/ml (p < 0.008) 42 DPI. There was no detectable IL-10 in CSF. IL-10 synthesis is thus stimulated both in the early and transitional stages of experimental trypanosomiasis. That IL-10 is produced in early stage disease is an interesting finding unlikely to be detected in humans where it is difficult to determine the exact time of infection. The IL-10 peak observed on day 42 of infection might indicate onset of parasite neuroinvasion coinciding with a peak in white blood cell counts in the blood and CSF.     

The effect of intestinal alkaline phosphatase on intestinal epithelial cells,macrophages and chronic colitis in mice

Aims

Intestinal alkaline phosphatase (IAP) is an intestinal brush border enzyme that is shown to function as a gut mucosal defense factor, but its defensive mechanism remains unclear. The aims of this study were to evaluate the effect of IAP on intestinal epithelial cells and macrophages, and on chronic colitis in interleukin-10-deficient (IL-10^−/−) mice.

Main methods

Human intestinal epithelial cells COLO 205 and peritoneal macrophages from IL-10^−/− mice were pretreated with IAP and then stimulated with lipopolysaccharide (LPS). IL-8 secretion from COLO205 cells and TNF-α, IL-6, IL-12 from peritoneal macrophages were measured by ELISA. Electrophoretic mobility shift assay was used to assess the DNA binding activity of NF-κB and IκBα phosphorylation/degradation was evaluated by immunoblot assay in COLO 205. For the in vivo study, colitis was induced in IL-10^−/− mice with piroxicam, the mice were then treated with 100 or 300 units of IAP by oral gavage for 2 weeks. Colitis was quantified by histopathologic scoring, and the phosphorylation of IκBα in the colonic mucosa was assessed using immunohistochemistry.

Key findings

IAP significantly inhibited LPS-induced inflammatory cytokine production in both IECs and peritoneal macrophages. IAP also attenuated LPS-induced NF-κB binding activity and IκBα phosphorylation/degradation in IECs. Oral administration of IAP significantly reduced the severity of colitis and down-regulated colitis-induced IκBα phosphorylation in IL-10^−/− mice.

Significance

IAP may inhibit the activation of intestinal epithelial cells and peritoneal macrophages, and may attenuate chronic murine colitis. This finding suggests that IAP supplementation is a potential therapeutic option for inflammatory bowel disease.     

Development of a semiochemical-based trapping method for the New Guinea sugarcane weevil, Rhabdoscelus obscurus in Guam

Abstract:  Aggregation pheromone of the Australian population of New Guinea sugarcane weevil, Rhabdoscelus obscurus (Boisduval), in conjunction with other semiochemicals, was used to develop an efficient trapping method for the weevil population in Guam. In a field experiment at Yigo, plastic bucket traps baited with the lure of the Australian R. obscurus population in combination with ethyl acetate and cut sugarcane captured significantly more weevils than traps baited with pheromone + ethyl acetate, pheromone + sugarcane or individual lure components alone. Traps baited with various semiochemical-based lures and treated with insecticide captured significantly greater numbers of weevils than those not treated with insecticide. Traps baited with cut sugarcane caught significantly more weevils than those without sugarcane. Semiochemical-based trapping in weevil management has potential either in mass trapping or as part of an integrated pest management (IPM) programme. Based on the present findings, a future line of work for the control of this weevil is proposed.     

cAMP-dependent protein kinases, their subunits, and cAMP-binding protein from four sources: a comparison of physical characteristics determined by polyacrylamide gel electrophoresis

The physical characteristics of cAMP-dependent protein kinases and their, regulatory subunits from calf uterus, human uterus, human mammary tumor, and rat pituitary and of cAMP-binding protein from calf uterus were determined by quantitative polyacrylamide gel electrophoresis in buffers containing the detergent, Triton X-100. In the four tissues, protein kinases of either type A¹, with molecular weight (M_r) = 200,000, or type B, of M_r = 80,000, or both, previously described were found. Trivial charge isomerism, or size isomerism, exists within each of the two classes, Protein Kinase A and B. The protein kinase recombined from the regulatory and catalytic subunits is not significantly different from the crude or isolated protein kinase. Protein Kinases A and B exist each in either one of the isozyme forms I and II but these are not reflected in polyacrylamide gel electrophoresis at pH 10.2. Protein Kinase B appears to be a product of the partial proteolysis of Protein Kinase A. The regulatory subunits of Protein Kinases A from the four tissues are distinct from those of Protein Kinases B. No physical distinction exists between regulatory subunits derived from isozyme forms I and II. cAMP-Binding Proteins A and B are physically indistinguishable, by polyacrylamide gel electrophoresis at pH 10.2, from the regulatory subunits of Protein Kinases A and B, respectively.     

DNAJC10基因在鼻咽癌中的表达及表达下调机制的研究

运用RT-PCR检测候选抑瘤基因DNAJC10在鼻咽癌组织中的表达,运用甲基化特异性PCR(MSPCR)技术、LOH和测序等技术分别检测DNAJC10基因在鼻咽癌组织中的甲基化状况、LOH和启动子突变情况.结果表明,DNAJC10基因在肿瘤组织中较对照慢性鼻咽炎组织表达明显下调(P<0.05).DNAJC10在鼻咽癌中不表现高甲基化,其LOH的缺失率为6.25%,突变率为66.7%.因此,DNAJC10基因的表达下调主要是其遗传改变(LOH和突变)所致.     

Involvement of IL-10 and Bcl-2 in resistance against an asbestos-induced apoptosis of T cells

To analyze the possibility that immunological alteration in asbestos-related diseases (ARDs) such as asbestosis (ASB) and malignant mesothelioma (MM) may affect the progression of cancers, a human adult T cell leukemia virus-immortalized T cell line (MT-2Org) was continuously exposed to 10 μg/ml of chrysotile-B (CB), an asbestos. After at least 8 months of exposure, the rate of apoptosis in the cells became very low and the resultant subline was designated MT-2Rst. The MT-2Rst cells were characterized by (i) enhanced expression of bcl-2, with regain of apoptosis-sensitivity by reduction of bcl-2 by siRNA, (ii) excess IL-10 secretion and expression, and (iii) activation of STAT3 that was inhibited by PP2, a specific inhibitor of Src family kinases. These results suggested that the contact between cells and asbestos may affect the human immune system and trigger a cascade of biological events such as activation of Src family kinases, enhancement of IL-10 expression, STAT3 activation and Bcl-2 overexpression. This speculation was partially confirmed by the detection of elevated bcl-2 expression levels in CD4 + peripheral blood T cells from patients with MM compared with those from patients with ASB or healthy donors. Further studies will be required to verify the role of T cells with enhanced bcl-2 expression in tumor progression induced by asbestos exposure.