Several tea polyphenols, particularly those containing galloyl, have antitumor affects via strong antioxidant and antiangiogenic activi-ties. Theaflavin-3, 3'-digallate (TF3), a theaflavin derivative in black tea, has 2 galloyl groups. Matrix metalloproteinases (MMPs) are associated with extracellular matrix degradation, cellular migration, and angiogenesis, and (-) -epigallocatechin-3-gallate (EGCG) is an inhibitor of MMP activity and secretion; thus one of its major actions is the inhibition of angiogenesis. However, there are few studies of angiogenesis in theaflavin derivatives. We investigated the effects of TF3 on angiogenesis in vitro. Angiogenesis was assayed using cocultured human umbilical vein endothelial cells with fibroblasts. Cells were cultivated in various concentrations of TF3 and EGCG in the presence or absence of vascular endothelial growth factor-A. After 11 days, MMP-2 and MMP-9 activities and the pro-MMP-2 protein in the medium were measured by gelatin zymography and immunoassay, respectively. Tube formation was markedly inhibited by 100 μmol/L TF3 or EGCG. Even at 10 iumolIL, TF3 or EGCG inhibited tube formation. The MMP-2 and MMP-9 activities were inhibited and pro-MMP-2 protein concentrations were reduced by TF3 or EGCG in a concentration-dependent manner, regardless of the presence of vascular endothelial growth factor. The effect of TF3 was similar to that of EGCG, indicating that the tube formation of endothelial cells was suppressed via decreased both MMP-2 and MMP-9 activities in vitro. Our results demonstrate antiangiogenic activity of TF3 in vitro, and suggest possible anti-tumor effects of TF3.

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To identify predictive factors of the recurrence of colorectal cancer, histopathological, biometric, and immunohistological examinations were conducted with colorectal cancer specimens at stage II or lower. The subjects were 42 male and 34 female patients (mean age 68.3 years) with colorectal cancer (stage II), who had undergone surgical removal of a tumor in the lower alimentary tract. The tumors were classified as colon carcinomas in 61 cases and rectal carcinomas in 15 cases. The clinical course of each case was followed for at least 3 years after surgery. Cases classified as recurrent (n=13, 17 % ) had obvious recurrence, such as metastatic tumors in internal organs. All other cases were classified as nonrecurrent. Tumors from all subjects were surgically extracted, and the invasive front of tumor tissue was observed macroscopically and excised for histopathological examination. After the specimens were fixed with formalin and embedded in paraffin, thin sections were cut and stained with hematoxylin and eosin for microscopy. In addition, nuclear morphometry was performed using a digital images and imaging software. Mean values were obtained for the number of tumor cell nuclei per unit area, nuclear area, diagonal width of the nuclei, length of the major axis, and roundness of the nuclei (atypia) . For immunological nuclear investigations, the invasive fronts were observed using β-catenin and classified into 3 grades. The chi-square test and Welch's t test of the m × n table were used for statistical analysis. In the recurrent cases, the mean number of tumor nuclei per unit area was lower, while the mean nuclear area, diagonal width, and length of the major axis were all significantly higher than in nonrecurrent cases. However, there was no difference in nuclear roundness. β-catenin expression in the invasive front of colorectal cancer specimens was Grade 0 for 40 cases, Grade 1 for 26 cases, and Grade 2 for 10 cases, with 11 (85%) of 13 recurrent cases positive and only 25 (40%) of 63 nonrecurrent cases positive. On the basis of these findings, the recurrent cases tended have tumor cells with enlarged nuclei and thus a high nucleus to cytoplasm ratio, while β-catenin-positive nuclei tended to be associated with recurrence. These characteristics are suggested predictors of recurrence of early stage colorectal cancer.

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Recent evidence suggests that decreased levels of adiponectin and elevated levels of C-reactive protein (CRP) and small, dense low-density lipoprotein cholesterol (sd-LDL-C) may be risk factors for the development of coronary heart disease (CHD) . This study sought to determine how these factors are associated with coronary events compared with LDL-C, an established potent risk factor, in stable CHD. LDL particle size, sd-LDL-C (assessed by the heparin-magnesium precipitation method), CRP, highmolecular weight adiponectin, apolipoproteins and hemoglobin A1c were compared among 219 stable CHD patients who had undergone coronary arteriography and 159 hypertensive patients without diabetes or CHD. None of the subjects received lipid-lowering drugs during the study. A coronary event was defined as a revascularization procedure within 6 months of blood measurement. Fasting LDL-C, sd-LDL-C, apolipoprotein B, hemoglobin A1c, and CRP were significantly higher in the patients with coronary events than in those without events. High-density lipoprotein cholesterol, apolipoprotein A-1 and adiponectin were significantly lower in the patients with coronary events than in those without events. LDL-C levels were similar between the non-CUD hypertensives and the CHD patients with events. Elevated sd-LDL-C was the only parameter found to be significantly associated with severe CHD independent of LDL-C, high-densty lipoprotein cholesterol, apolipoprotein B, adiponectin and CRP by multiple logistic regression analysis. These results suggest that sd-LDL-C is superior to LDL-C and adiponectin for predicting the progression of stable CHD.

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We examined the effect on pH and temperature of deoxygenates and desiccants after the addition of artificial stomach fluid (0.01N HCl /0.9% NaCI solution), tap water, orange juice, and milk. Surface temperature was monitored with an iron-constantan thermometer with analogue-digital converter. RAYM, which was made of calcium oxide, showed significantly increased surface temperature with addition of artificial stomach fluid, whereas the addition of orange juice significantly reduced pH. The addition of 500 mL of orange juice to 3 g of Ageless demonstrated acidification of surface pH without increasing surface temperature. In Silica Gel (R), temperature was modestly increased and pH was elevated by milk. With respect to Ageless we observed slight increases of temperature and pH rose with the addition of tap water. Our results suggest that physiological damage could be reduced by orange juice when deoxygenates and / or desiccants are ingested.

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We examined which regimen of triweekly or biweekly docetaxel in combination with irinotecan demonstrates superiority of the antitumor activity and toxicity in patients with refractory or relapsed advanced non-small-cell lung cancer (NSCLC) . Patients with previously treated NSCLC of stage III or IV were eligible if they had a performance status of 2 or less, and were 75 years or younger. Patients were treated every 3 weeks with docetaxel (50 mg / m² on day 2) plus irinotecan (50 mg / m2 on days 1 and 8) or every 4 weeks with docetaxel (33 mg / m² on days 2 and 16) plus irinotecan (50 mg / m² on days 1 and 15) . Fifty patients were enrolled. Patient characteristics were not significantly different between the triweekly and biweekly arms. The overall response rates were 6.7 % and 14.3 %, times to progression were 2 months and 3 months, median survival times were 5 months and 8 months, and 1-year survival rates were 20% and 30% in the triweekly and biweekly arms, respectively. There were no differences in response rates, TTP, and survival between arms. In the triweekly arm, grade-3 or -4 leukopenia and diarrhea occurred more frequently than in the biweekly arm. In both arms, 2 patients had grade 3 to 4 drug-induced interstitial pneumonia but recovered after receiving steroid therapy. There were no treatment-related deaths. The biweekly arm demonstrated similar efficacy and better tolerability than the triweekly arm and can be recommended as an alternative treatment option in patients with refractory or relapsed NSCLC.

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Acute myeloid leukemia (AML) is a heterogeneous clonal disorder of hematopoietic progenitor cells and is the most common malignant myeloid disorder in adults. The receptor tyrosine kinase c-kit (CD117) is believed to be critical for the development of full-blown leukemia. However, the prevalence and clinical significance of c-kit expression in AML remains unclear. In this study, we examined whether c-kit expression could be a prognostic marker of AML using our original pathological index, compared with the FLT3/ITD mutation, which is a poor prognostic marker of AML. The positive rate of c-kit was 89.1%, which was more than 10% of the pathological index. Moreover, the pathological index of c-kit in AML patients with the FLT3/ITD mutation was 74.3%, which was significantly higher than in patients without the FLT3/ITD mutation at 53.6%. We suggest that the pathological index of c-kit is a useful indication of this prognostic marker.

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