Recently, much attention has been paid to nonmyeloablative allogeneic stem cell transplantation for the treatment of metastatic renal cancer. Mature donor T cells cause graftversus-host disease (GVHD) although they are also the main mediators of the beneficial graft-versus-tumor activity associated with this treatment. Hence, the segregation of the graftversus-tumor activity from GVHD is an important challenge in managing the clinical course of treatment. We previously reported a series of studies regarding the allograft tolerance induced by allogeneic spleen cells (with bone marrow cells) and cyclophosphamide in mice. Here, we show a modified cyclophosphamide-induced tolerance system for the treatment of murine renal cell carcinoma, RENCA, by shifting the equal balance between graft-versus-host and host-versus-graft reactions toward graft-versus-host reaction with donor lymphocyte infusion. Our results clearly show the antitumor activity against RENCA with only low levels of mixed chimerism in the periphery and the in vivo and in vitro acquired immunity against RENCA even when mixed chimerism is almost undetectable. Because the withdrawal of mixed chimerism reduces the risk of GVHD, the antitumor activity is thus sequentially segregated from the initial GVHD in our model. We believe that this is the first unique model system of nonmyeloablative allogeneic hemopoietic cell transplantation to ever be reported for the treatment of renal cancer. (Cancer Res 2005; 65(21): 10032-40)

Objective : We examined the clinical outcomes and the learning curve for a laparoscopic adrenalectomy (LA) in 103 consecutive cases performed by three surgeons at our institute, according to the type of adrenal disorder. Patients and Methods : One hundred and three patients with adrenal tumors, including 38 cases of primary aldosteronism, 33 cases of Cushing syndrome (including preclinical Cushing syndrome), 15 cases of pheochromocytoma, and nine cases of nonfunctioning adenoma were evaluated, while focusing on the approaches, intraoperative and postoperative data, and the learning curve of LA, according the type of adrenal disorder. Results : There was no significant difference in the operation time, estimated blood loss, incidence of conversion to open surgery and blood transfusion, or postoperative recovery among the patients treated by LA for aldosteronoma, Cushing adenoma, pheochromocytoma, and non-functioning adenoma. In the cases of aldosteronoma and Cushing adenoma, the learning curve for the operation time and blood loss in each operator tended to decrease as the number of operations increased. On the other hand, in the cases treated by LA for pheochromocytoma, no trends in either the operation time or blood loss were observed. However, there has been neither any conversion to open surgery nor blood transfusion in cases treated by LA since 1998 (our 42nd case), even after the changes in the operators. Conclusions : Our results clearly indicate that LA is becoming safer than before, probably due to improvements in the technique, education, and training of surgeons, in addition to the increased number of cases now treated by LA.

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Nonmyeloablative allogeneic stem cell transplantation (SCT) has been used for various malignancies, although detailed mechanisms of antitumor effects remain unclear. We showed that a nonmyeloablative allogeneic SCT regimen, which consists of mixed chimerism induced by an injection of donor spleen and bone marrow cells followed by cyclophosphamide treatment and a donor lymphocyte infusion (DLI), exerted antitumor effects on established murine bladder tumor, MBT-2. An expansion of donor CD4 T cells accompanied by transient but vigorous IFN-γ production was detected shortly after DLI. In vivo neutralization of IFN-γ or depletion of CD4 T cells from DLI abolished the antitumor effects, indicating an indispensable role of donor CD4 T cells producing IFN-γ. Donor as well as host CD8 T cells accumulated in the tumor region with time. Importantly, depletion of CD8 T cells from DLI did not reverse the suppression of tumor growth, indicating that CD4 T cells play a more essential role in mediating early antitumor effects. Furthermore, tumor-specific response of host CD8 T cells was suggested. These results not only provide the first evidence of nonmyeloablative allogeneic SCT for the treatment of bladder tumor but also elucidate detailed mechanisms of antitumor effects provoked by DLI. [Cancer Res 2009;69(12):5151-8]

This multi-institutional study aimed to identify prognostic factors for cabazitaxel treatment of castration-resistant prostate cancer (CRPC). This study included 74 Japanese patients with CRPC who were treated with cabazitaxel between 2014 and 2017. Associations between clinicopathological factors including serum markers and progression-free survival (PFS) and overall survival (OS) were investigated. On multivariate analysis, high Gleason score [≥9 vs. ≤7; hazard ratio (HR), 95% confidence interval (CI): 2.00 (1.01–4.34); P = 0.047], presence of pain [HR, 95% CI: 2.02 (1.14–3.58); P = 0.016], and lactate dehydrogenase (LDH) level [HR, 95% CI: 47.31 (3.79–577.49); P = 0.0019] were significantly associated with PFS. Similarly, number of docetaxel cycles [HR, 95% CI: 0.050 (0.0037–0.45); P = 0.0057], performance status [≥2 vs. 0; HR, 95% CI: 5.07 (1.57–16.24); P < 0.0001], and LDH level [HR, 95% CI: 2946 (50–420994); P = 0.0001] were significantly associated with OS. This study showed that LDH level is robustly prognostic for both PFS and OS in cabazitaxel chemotherapy for CRPC.