Interferon treatment for Japanese patients with favorable-risk metastatic renal cell carcinoma in the era of targeted therapy

PURPOSE: Single-agent interferon (IFN) is no longer regarded as a standard option for first-line systemic treatment of metastatic renal cell carcinoma (RCC) in Western countries. However, some patients with favorable-risk RCC may still achieve complete and long-lasting remission in response to IFN treatment. The present study compared favorable-risk Japanese patients with metastatic RCC Japanese patients who had been treated with IFN or tyrosine kinase inhibitor (TKI) therapy as a first-line systemic therapy. MATERIALS AND METHODS: From 1995 to 2014, a total of 48 patients with favorable risk as defined by the Memorial Sloan Kettering Cancer Center criteria who did not receive adjuvant systemic therapy were retrospectively enrolled in this study. We assessed the tumor response rate, progression-free survival (PFS), and overall survival (OS). RESULTS: The objective response rate for first-line therapy was 29% in the IFN group and 47% in the TKI group, but this difference did not reach the level of statistical significance. Median OS for IFN and TKI was 71 and 47 months, respectively (p=0.014). Median first-line PFS for IFN and TKI was 20 and 16 months, respectively (no significant difference). First-line IFN therapy did not prove inferior to TKI therapy in terms of OS according to metastatic sites. CONCLUSIONS: IFN is associated with a survival benefit in Japanese patients with favorable-risk metastatic RCC in the era of targeted therapy. Further prospective study is needed.

Mechanisms of metastasis suppression by introduction of human chromosome 10 into rat prostate cancer / 亚洲男科学杂志(英文版)

<p><b>AIM</b>The metastatic ability of a Dunning R-3327 rat prostate cancer subline (AT6.3) was suppressed by the introduction of human chromosome 10, when these hybrid cancer cells were injected subcutaneously into nude mice (Nihei et al., Genes Chromosomes Cancer 14:112-119, 1995). The present study was undertaken to clarify which step of metastasis was suppressed in the human chromosome 10-containing microcell hybrids (AT 6.3-10 clones).</p><p><b>METHODS</b>Gelatin zymography, an in vitro invasion assay using a Boyden chamber and an intravenous metastasis assay involving the injection of hybrid cells into nude mice were performed.</p><p><b>RESULTS</b>Gelatin zymography revealed that AT6.3-10 microcell hybrid clones expressed the 72 kD type IV collagenase (MMP-2) at an almost equal level as control microcell hybrid clones. Both the invasiveness as measured by the invasion assay and the number of lung metastases as measured by the intravenous metastasis assay of AT6.3-10 hybrid clones were significantly less than those of the AT6.3 parental clone.</p><p><b>CONCLUSION</b>The human chromosome 10 suppresses both the local invasion and the metastatic process after entry into the blood circulation of rat prostate cancer. This decrease in local-invasive ability does not seem to require a decrease in MMP-2 activity.</p>

Suppression of metastasis of rat prostate cancer by introduction of human chromosome 13 / 亚洲男科学杂志(英文版)

<p><b>AIM</b>Chromosome 13 is one of the most frequently altered chromosomes in prostate cancer. The present study was undertaken to examine the role of human chromosome 13 in the progression of prostate cancer.</p><p><b>METHODS</b>Human chromosome 13 was introduced into highly metastatic rat prostate cancer cells via microcell-mediated chromosome transfer.</p><p><b>RESULTS</b>Microcell hybrid clones containing human chromosome 13 showed suppression of metastasis to the lung without any suppression of tumorigenicity, except for one clone, which contained the smallest sized human chromosome 13 and did not show any suppression on lung metastasis. Expression of two known tumor suppressor genes, BRCA2 and RB1, which map to chromosome 13, was examined by reverse transcription- polymerase chain reaction analysis. BRCA2 was expressed only in the metastasis-suppressed microcell-hybrid clones, whereas RB1 was expressed in all clones.</p><p><b>CONCLUSION</b>Human chromosome 13 contains metastasis suppressor gene(s) for prostate cancer derived from rat. Furthermore, the RB1 gene is unlikely to be involved in the suppression of metastasis evident in this system.</p>