Novel Mechanism Supporting Therapeutic Effects of Glycyrrhizin in Acute or Chronic Hepatitis

Glycyrrhizin (GL) isolated from the roots of licorice plant (Glycyrrhiza glabra L.) has been traditionally used for treating peptic ulcer, hepatitis, and pulmonary bronchitis. In addition to the protective effects of GL against liver injury or cancer proliferation by the membrane stabilization or via progesterone‐receptor membrane component 1 (PGRMC1), the present chapter reports its new therapeutic mechanism through high‐mobility group protein 1 (HMGB1) to which GL directly binds. In this study, we evaluated inflammation‐promoting activity of HMGB1 and blockade of extracellular release of HMGB1 by GL in lipopolysaccharide (LPS)/d‐galactosamine (GalN)‐triggered mouse liver injury. In this experimental hepatitis model, apoptotic response of hepatocytes through the binding of HMGB1 protein to Glutathione transferase omega 1 (Gsto1), an apoptosis‐associated gene, promoter region is caused, serum AST and ALT activities significantly increased, and GL‐treatment prevented the apoptosis and inflammatory infiltrates induced with LPS/GalN‐injection by disturbing the binding of HMGB1 protein to Gsto1 promoter sequence. Analysis with chromatin immunoprecipitation (ChIP)‐assay revealed inhibiting the binding of HMGB1 protein to Gsto1 by the binding of GL to HMGB1

Clonal Heterogeneity in Drug Sensitivity of Primary and Metastatic Murine Tumor Cells Using a Clonogenic Assay

The heterogeneity with respect to the sensitivity to a cytotoxic agent of clones derived from a mouse fibrosarcoma tumor (MCA-F?) and its individual metastatic lung colonies has been examined. After 1 hr exposure of mitomycin C (MMC), the plating efficiency (PE) of parental tumor cell clones and metastatic cell clones were measured respectively, suggesting that the degree of clonal heterogeneity of primary tumor cells which showed different ancholage-independency was lower than that of metastatic tumors. The drug sensitivity of parental tumor cell clones also showed their heterogeneity and in the individual metastatic lung tumor cell clones as well, but with a rather high resistance. One (MCA-F-M2) out of 4 colonies in the lung, especially showed significantly high % PE in a clonogenic assay using 1 hr MMC exposure at 0.1 μg/ml concentration (mean % PE=19.7; P<0.005) and its clones showed almost the same homogeneous sensitivity within a growing colony in the lung. While, there existed not a small population of drug sensitive clones within these metastatic lesions. These findings indicate the clonal chemotherapeutic heterogeneity in metastatic lesions, and may provide, serious implications for the administration of antitumor drugs on the early differentiation of tumors

Aberrant expression and potency as a cancer immunotherapy target of alpha-methylacyl-coenzyme A racemase in prostate cancer

Alpha-methylacyl-CoA racemase (AMACR) is an enzyme playing an important role in the beta-oxidation of branched-chain fatty acids and fatty acid derivatives. High expression levels of AMACR have been described in various cancers, including prostate cancer, colorectal cancer and kidney cancer. Because of its cancer-specific and frequent expression, AMACR could be an attractive target for cytotoxic T-lymphocyte (CTL)-based immunotherapy for cancer. In the present study, we examined the induction of AMACR-specific CTLs from prostate cancer patients' peripheral blood mononuclear cells (PBMCs) and determined HLA-A24-restricted CTL epitopes

Variable Stars in the Magellanic Clouds: Results from OGLE and SIRIUS

We have performed a cross-identification between OGLE-II data and single-epoch SIRIUS JHK survey data in the LMC and SMC. After eliminating obvious spurious variables, we determined the pulsation periods for 9,681 and 2,927 variables in the LMC and SMC, respectively. Based on these homogeneous data, we studied the pulsation properties and metallicity effects on period-K magnitude (PK) relations by comparing the variable stars in the LMC and SMC. The sample analyzed here is much larger, and we found the following new features: (1) variable red giants in the SMC form parallel sequences on the PK plane, just like those found by Wood (2000) in the LMC; (2) both of the sequences A and B of Wood (2000) have discontinuities, and they occur at the K-band luminosity of the TRGB; (3) the sequence B of Wood (2000) separates into three independent sequences B+- and C'; (4) comparison between the theoretical pulsation models (Wood et al. 1996) and observational data suggests that the variable red giants on sequences C and newly discovered C' are pulsating in the fundamental and first overtone mode, respectively; (5) the theory can not explain the pulsation mode of sequences A+- and B+-, and they are unlikely to be the sequences for the first and second overtone pulsators, as was previously suggested; (6) the zero points of PK relations of Cepheids in the metal deficient SMC are fainter than those of LMC ones by ~0.1 mag but those of SMC Miras are brighter than those of LMC ones by ~0.13 mag, which are probably due to metallicity effects.Comment: 9 pages, 10 figures, accepted for publication in MNRAS. High resolution version is available at: http://www.ioa.s.u-tokyo.ac.jp/~yita/scr/astro/papers/RefereedPaper/yitaMD250 .pd