Reona Fujii

HSP DNAJB8 Controls Tumor-Initiating Ability in Renal Cancer Stem-like Cells

Cancer stem-like cells (CSC) are a small population of cancer cells with superior tumor initiating, self-renewal, and differentiation properties. In this study, we show that the cancer-testis antigen and HSP40 family member DNAJB8 contributes to the CSC phenotype in renal cell carcinoma (RCC). DNAJB8 overexpression increased the percentage of side population (SP) cells representing CSCs in RCC cells, enhancing their tumor-initiating ability. Conversely, attenuation of DNAJB8 decreased SP cells and reduced tumor-initiating ability. The utility of DNAJB8 as an immunologic target was established in DNA vaccination experiments. Compared with immunization with the tumor-associated antigen survivin, which was expressed in both CSCs and non-CSCs in RCC, immunization with Dnajb8 expression plasmids yielded stronger antitumor effects. Together, our findings suggest that DNAJB8 plays a role in CSC maintenance and that it offers a candidate for CSC-targeting immunotherapy in RCC.

Insulin resistance increases the risk of urinary stone formation in a rat model of metabolic syndrome

To investigate the association between metabolic syndrome and urinary stone disease, and whether insulin resistance associated with adiposity affects the risk of urinary stone formation, using a rat model of metabolic syndrome.

Efficiency of G2/M-related tumor-associated antigen-targeting cancer immunotherapy depends on antigen expression in the cancer stem-like population

The aim of this study was to establish a novel efficient cancer DNA vaccine approach. Many tumor-associated antigens (TAAs) have been reported; however, there is little information of the efficiency of each TAA. Normal cells barely undergo mitosis, whereas cancer cells divide frequently and grow well. Thus, G2/M-related antigens are cancer cell-specific and are regarded to be suitable candidates as targets of cancer immunotherapy. In this study, we compared the efficiencies of G2/M-related antigens including Birc5, Aurka, Nke2 and Plk1 by using a DNA vaccination model. Mice that had been immunized with G2/M-related antigens coding plasmid were challenged with CT26 colon cancer cells. Interestingly, Birc5- and Aurka-immunized mice showed an anti-tumor effect, whereas Nek2- and Plk1-immunized mice did not show any anti-tumor effect. We investigated the expression of G2/M-related antigens in cancer stem-like cell (CSC)/cancer-initiating cell (CIC) population to verify the difference in the anti-tumor effect. CSCs/CICs were isolated as side population (SP) cells using Hoechst 33342 dye from CT 26 cells. It was found that Birc5 and Aurka are expressed in both CSCs/CICs and non-CSCs/CICs (shared antigens), whereas Nek2 and Plk1 are expressed preferentially in non-CSCs/CICs (non-CSC antigens). Therefore, antigen expression in the CSC/CIC population might be related to the anti-tumor efficiency of cancer immunotherapy. Furthermore, we established a heat shock protein (Hsp90)-fused Birc5 plasmid to improve anti-cancer immunity. Birc5 fused to the N-terminal region of Hsp90 showed a stronger anti-tumor effect, whereas Birc5 fused to the C-terminal region of Hsp90 did not show enhancement compared with Birc5. These observations indicate that expression in the CSC/CIC population is essential to achieve tumor regression and that fusing antigens to the N-terminal region of Hsp90 enhances the anti-tumor effect.

Dendritic cells with transduced survivin gene induce specific cytotoxic T lymphocytes in human urologic cancer cell lines.

OBJECTIVES To investigate whether survivin-specific cytotoxic T lymphocytes (CTLs) could be induced by dendritic cells (DCs) transduced with survivin gene by adenoviral vector, and whether these CTLs would display cytotoxic activities against human urologic cancer cell lines. Survivin, a member of the inhibitor of apoptosis protein family, is expressed in most malignancies, but not in normal tissue. METHODS Adenoviral vector encoding the human survivin gene was generated. Human DCs from healthy donors were transduced with human survivin gene by infection with adenoviral vector encoding the human survivin gene using the centrifugal method. Survivin-specific CTLs were induced from autologous peripheral blood mononuclear cells by DCs transduced with the survivin gene. The ability of CTLs to lyse cancer cell lines was assessed using the (51)Cr-release assay. RESULTS DCs transduced with survivin gene could induce survivin-specific CTLs against various urologic malignancies such as bladder, kidney, and prostate cancer cells. This cytotoxic activity could be blocked by anti-CD8 and anti-major histocompatibility complex class I antibodies. We also found that this cytotoxic activity was specific for the survivin protein and human leukocyte antigen haplotype. CONCLUSIONS DCs transduced with the survivin gene induced potent survivin-specific CTL responses in vitro. This suggests that cancer immunotherapy targets for survivin might offer a novel approach to treating various urologic cancers.

PSA at postoperative three months can predict biochemical recurrence in patients with pathological T3 prostate cancer following radical prostatectomy

Objectives:  To identify the prognostic factors and determine which pT3 prostate cancer patients can be safely followed up after surgery without any adjuvant treatment.

Bacillus Calmette‐Guérin cell‐wall skeleton enhances the killing activity of cytotoxic lymphocyte‐activated human dendritic cells transduced with the prostate‐specific antigen gene

To determine whether dendritic cells (DC) transduced with the prostate‐specific antigen (PSA) gene can induce PSA‐specific cytotoxic lymphocytes (CTL) against prostate cancer cells, and whether bacillus Calmette‐Guérin (BCG) cell‐wall skeleton (CWS) can enhance the maturation of DC‐PSA and the killing activity of subsequently induced PSA‐specific CTL.

IL‐23 gene therapy for mouse bladder tumour cell lines

•  To evaluate the antitumour effects of IL‐23 gene transfer into mouse bladder carcinoma (MBT2) cells. •  To investigate the mechanisms underlying the subsequent constitutive secrection of IL‐23 by the MBT2 cells

THE FEASIBILITY AND USEFULNESS OF JAPAN ASSOCIATION FOR THE SURGERY OF TRAUMA (JAST) CLASSIFICATION FOR BLUNT RENAL TRAUMA

RESULTS: The average follow-up was 50 months (range 12 to 132 months). The stricture etiology was catheter in 20 (32.3%) cases, unknown in 19 (32.3%), instrumentation in 17 (27.4%), trauma in 4 (6.5%), radiotherapy in 1 (1.6%) and infection in 1 (1.6%). Stricture length was: 4- 6 cm in 13 (21%), 3-<4 cm in 10 (16.1%), 2-<3 cm in 8 (12.9%), 1<2cm in 2 (3.2%). Fifty-one patients (82.2%) underwent dilation (12.9%), internal urethrotomy (17.7%), urethroplasty (4.8%) or multiple treatments (46.9%) before referral to our center. Out of 62 cases, 47 (75.8%) were successful and 15 (24.2%) failures. Out of 18 cases that underwent one-stage dartos

QUALITY OF LIFE ANALYSIS OF PATIENTS WHO UNDERWENT HIGH DOSE RATE BRACHYTHERAPY WITH EXTERNAL BEAM RADIOTHERAPY (HDR+EBRT) COMPARING WITH THOSE WHO HAD RETROPUBIC RADICAL PROSTATECTOMY (RRP)

The mean age of BT and RP treated patients was 68 and 64 years. 71,7% (n=620) of RP treated patients had non-nerve-sparing surgery. 89,3% (n=303) and 90,6% (n=770) of the BT and RP treated patients had clinical tumor stage of cT1a-2b. Significant better results in concern of increased voiding frequency (BT 67,8% vs. RP 60,4%), nocturia (BT 43,7% vs. RP 28,9%) and urge symptoms (BT 47,4% vs. RP 36,4%) were recognized at the RP treated group. Significant better results in term of incontinence was achieved in the BT group (BT 11,6% vs. RP 15,6%), but interestingly the group with nerve sparing RP showed almost similar results to BT (BT 11,6% and nerve-sparing RP 11,2%). Absence of erections was reported by 43% of the BT, 85% of RP without nerve sparing, 45% of RP with unilateral nerve sparing and 38% of the RP with bilateral nerve sparing. CONCLUSIONS: In regards to functional outcome BT causes significant higher rates of irritative voiding symptoms. However continence and Preservation of erectile function seems superior in BT compared to RP patients without nerve sparing. Nevertheless differences became minor or insignificant in RP with bilateral nerve sparing.