Kyohei Araki

Anticancer Effects of Green Tea and the Underlying Molecular Mechanisms in Bladder Cancer

Green tea and green tea polyphenols (GTPs) are reported to inhibit carcinogenesis and malignant behavior in several diseases. Various in vivo and in vitro studies have shown that GTPs suppress the incidence and development of bladder cancer. However, at present, opinions concerning the anticancer effects and preventive role of green tea are conflicting. In addition, the detailed molecular mechanisms underlying the anticancer effects of green tea in bladder cancer remain unclear, as these effects are regulated by several cancer-related factors. A detailed understanding of the pathological roles and regulatory mechanisms at the molecular level is necessary for advancing treatment strategies based on green tea consumption for patients with bladder cancer. In this review, we discuss the anticancer effects of GTPs on the basis of data presented in in vitro studies in bladder cancer cell lines and in vivo studies using animal models, as well as new treatment strategies for patients with bladder cancer, based on green tea consumption. Finally, on the basis of the accumulated data and the main findings, we discuss the potential usefulness of green tea as an antibladder cancer agent and the future direction of green tea-based treatment strategies for these patients.

MP65-01 4N1K-PEPTIDE DERIVED FROM THROMBOSPONIDN-2 IS ASSOCIATED WITH MALIGNANT AGGRESSIVENESS AND PROGNOSIS IN BLADDER CANCER

RESULTS: Median follow-up of the series was 131.8 months (120-194). During the surveillance period, 55 patients developed BCR (33%) and 6 metastatic recurrence (3.6%). Overall, three patients died of PCa (1.8%), and 22 due to other causes (13%). Expression levels of 15800 genes differed between clinically localized and locally advancedmetastatic PCa groups (FDR<0.1). A total of 35 differently expressed genes with a fold change value > 5 and 10 genes previously described in literature were selected to be validated in an additional set of samples. Two genes were found to be independent prognostic factors of BCR (MSMB, HR1⁄41.75, p1⁄40.04) (FOS, HR1⁄41.73, p1⁄40.05) and two genes were found to be predictors of metastatic recurrence (KRT17, HR1⁄47.17, p1⁄40.03) (SERPINE1, HR1⁄45.54, p1⁄40.06). CONCLUSIONS: Gene expression levels in PCa tissue can be useful for distinguishing patients with clinically localized disease who will develop BCR or metastatic recurrence after radical prostatectomy. These gene expression biomarkers could have potential clinical utility for identifying the subset of patients that would benefit from closer surveillance and adjuvant therapy.

MP54-07 HEPATOCYTE GROWTH FACTOR RECEPTOR/C-MET IS ASSOCIATED WITH MALIGNANT AGGRESSIVENESS VIA REGULATION OF CYCLOOXYGENASE-2, HEMEOXYGENASE-1, AND PROGRAMMED DEATH LIGAND 1 IN PATIENTS WITH BLADDER CANCER

(IHC) on tissue microarrays were used to confirm tissue sampling and the gene expression analysis. RESULTS: Unsupervised consensus clustering yielded four distinct consensus clusters (CC) or subtypes: CC1-Basal, CC2Luminal, CC3-Immune and CC4-Scar-like. The CC1-Basal and CC2Luminal subtypes expressed genes consistent with a basal-like (KRT5/ 6, KRT14) and a luminal-like (GATA3, PPARG) phenotype, respectively. The CC3-Immune subtype had the highest immune activity, including T-cell infiltration and checkpoint molecules (CTLA4, CD80). Finally, the CC4-Scar-like profile was consistent with non-neoplastic scar samples, expressing genes associated with wound healing / scarring (MYH11, SHH, CNN1). Approximately the same numbers of pre-NAC basaland luminal-like samples remained static (CC1 or CC2) with respect to subtype or were highly immune-infiltrated (CC3) in the post-NAC setting. In the post-NAC setting, luminal-like pre-NAC samples were more likely adopt a scar-like character (CC4). CONCLUSIONS: This study expands our knowledge of cisplatin-resistant MIBC by suggesting molecular subtypes to understand the biology of these tumors. Although these molecular subtypes imply consequences for adjuvant treatments, this ultimately needs to be tested in clinical trials.

Pathological significance and prognostic roles of densities of CD57+ cells, CD68+ cells, and mast cells, and their ratios in clear cell renal cell carcinoma

The immune system is closely associated with malignant behavior in renal cell carcinoma (RCC). Therefore, understanding the pathological roles of immune cells in tumor stroma is essential to discuss the pathological characteristics of RCC. In this study, the clinical significance of densities of CD57+ cells, CD68+ cells, and mast cells, and their ratios were investigated in patients with clear cell RCC. The densities of CD57+, CD68+, and mast cells were evaluated by immunohistochemical techniques in 179 patients. Proliferation index, apoptotic index, and microvessel density were evaluated by using anti-Ki-67, anti-cleaved caspase-3, and anti-CD31 antibodies, respectively. The density of CD57+ cell was negatively correlated with grade, pT stage, and metastasis, although densities of CD68+ cell and mast cell were positively correlated. Ratios of CD68+ cell/CD57+ cell and mast cell/CD57+ cell were significantly correlated with grade, pT stage, and metastasis. Survival analyses showed that the CD68+ cell/CD57+ cell ratio was a significant predictor for cause-specific survival by multivariate analyses (hazard ratio = 1.41, 95% confidence interval = 1.03-1.93, P = .031) and was significantly correlated with proliferation index, apoptotic index, and microvessel density (r = .47, P <. 001; r = -.31, P < .001; and r = .40, P < .001, respectively). In conclusion, CD57+ cells, CD68+ cells, and mast cells played important roles in malignancy in clear cell RCC. The CD68+ cell/CD57+ cell ratio was strongly correlated with pathological features and prognosis in these patients because this ratio reflected the status of cancer cell proliferation, apoptosis, and angiogenesis.