Masahiro Shiba

Sesquiterpene lactone parthenolide suppresses tumor growth in a xenograft model of renal cell carcinoma by inhibiting the activation of NF-κB

The transcription factor nuclear factor‐κB (NF‐κB) has been shown to be constitutively activated in various human malignancies, including leukemia, lymphoma and a number of solid tumors. NF‐κB regulates the transcriptional of genes important for tumor invasion, metastasis and chemoresistance. The sesquiterpene lactone parthenolide, an inhibition of NF‐κB, has been used conventionally to treat migraines and inflammation. In this study, renal cancer cell lines OUR‐10 and ACHN were used for in vitro experiments to evaluate growth‐inhibitory effects of parthenolide. An OUR‐10 xenograft model in nude mice was also used to investigate the in vivo growth‐inhibitory effects of parthenolide. Apoptosis in response to treatment of OUR‐10 cells with parthenolide was confirmed. Localization of NF‐κB in response to parthenolide treatment was examined of by immunofluorostaining of OUR‐10 cells with antibody against NF‐κB p65 and by Western blot analysis of OUR‐10 cell and tumor nuclear and cytosol fraction. Parthenolide effectively inhibited proliferation of cultured OUR‐10 cells and triggered apoptosis in vitro. Subcutaneous injection or oral administration of parthenolide showed significant tumor growth inhibition in the xenograft model via decreased production of interleukin‐8 (IL‐8) or vascular endothelial growth factor (VEGF). Immunohistochemistry and Western blot analysis showed decreased nuclear localization of NF‐κB and phosphorylated NF‐κB protein and subsequently expression of MMP‐9, Bcl‐xL and Cox‐2 in response to parthenolide treatment. These results indicate that parthenolide is a useful in the treatment of renal cell carcinoma and acts via inhibition of NF‐κB.

The Growth-Inhibitory Effects of Dexamethasone on Renal Cell Carcinoma In Vivo and In Vitro

Background: Recently, several kinase inhibitors have been reported to exert stronger growth inhibitory effects on metastatic renal cell carcinomas (RCCs) than cytokines such as interferons (IFNs) and interleukin-2 (IL-2). On the contrary, the adverse effects of these drugs are also severe. The aim of this study is to analyze the growth-inhibitory effects of DEXamethasone (DEX) on RCC in vivo and in vitro. Methods: The MTT assay was performed using three RCC cell lines, OUR-10, Caki-1, and NC65. OUR-10 cells were subcutaneously transplanted to the dorsal area of nude mice. The nuclear translocation of glucocorticoid receptor (GR) and NF-κ B was examined using appropriate antibodies. Concentrations of interleukin-6 (IL-6), IL-8, and vascular endothelial cell growth factor (VEGF) in the conditioned media and cytosol were measured by enzyme-linked immunosorbent assay (ELISA). Results: All three RCC cell lines responded to DEX treatment. The growth of OUR-10 xenografts was significantly inhibited by administration of DEX. GR was translocated into the nucleus on DEX treatment. Intracellular IL-6, as well as IL-6 in the conditioned medium, decreased in OUR-10 cells following treatment with increasing amounts of DEX. Concentrations of IL-8 and VEGF in the conditioned medium of OUR-10 and NC65 cells also decreased following DEX treatment, with the inhibition of nuclear translocation of NF-κ B. Conclusion: DEX treatment is a candidate for advanced RCC therapy by inhibiting the activation of NF-κ B and its downstream products such as IL-6, IL-8 and VEGF.

Decreased immunostaining for macrophage scavenger receptor is associated with poor prognosis of prostate cancer

The aim of this study is to evaluate the expression of the macrophage scavenger receptor (MSR) in prostate needle biopsy specimens as a possible prognostic factor for prostate cancer. As MSR reportedly has a role in recognizing foreign pathogenic substances, MSR‐positive inflammatory cells are often detected in solid tumours, and there is a correlation between the relative risk of prostate cancer and polymorphism of the MSR gene.

Type-I interferon receptor expression : Its circadian rhythm and downregulation after interferon-α administration in peripheral blood cells from renal cancer patients

Objectives:  To investigate the regulation of interferon‐α (IFN‐α) receptor expression in metastatic renal cell carcinoma (RCC) after IFN‐α administration.

Non-synchronous Double Adenoma of the Parathyroid Gland

A 46‐year‐old female underwent an excision of a parathyroid adenoma diagnosed as recurrent primary hyperparathyroidism 24 years after the initial excision of a parathyroid adenoma. We report a case of non‐synchronous double adenomas of the parathyroid glands documented histopathologically.

INCREASED INFILTRATION OF TUMOR-ASSOCIATED MACROPHAGES IS ASSOCIATED WITH POOR PROGNOSIS OF CARCINOMA IN SITU OF BLADDER TREATED WITH INTRAVESICAL BACILLUS CALMETTE- GUÉRIN

946 INCREASED INFILTRATION OF TUMOR-ASSOCIATED MACROPHAGES IS ASSOCIATED WITH POOR PROGNOSIS OF CARCINOMA IN SITU OF BLADDER TREATED WITH INTRAVESICAL BACILLUS CALMETTEGUERIN Hitoshi Takayama*, Norio Nonomura, Masatoshi Mukai, Akira Nagahara, Masahiro Shiba, Daizo Oka, Yasutomo Nakai, Masashi Nakayama, Kazuo Nishimura, Akihiko Okuyama. Suita, Japan. INTRODUCTION AND OBJECTIVE: Tumor-associated macrophages (TAM) have been shown to positively or negatively regulate the growth of various malignant cells. TAM can produce various growth factors and cytokines. However, TAM in carcinoma in situ of bladder (CIS) progression is unclear. Today, intravesical Bacille CalmetteGuerin (BCG) therapy is the principal treatment for CIS. Although, immunotherapy with BCG has resulted in complete tumor regression in more than 70% of treated patients with CIS, half of BCG failures had progression to muscle invasive disease. Previous studies revealed that urinary inteleukin-2 and inteleukin-8 were prognostic factor for CIS. However, even with use of these prognostic factors, a decision