Significance of timing of therapeutic line on effectiveness of nivolumab for metastatic renal cell carcinoma

Objectives:This study aimed to clarify the significance of therapeutic timing on the effectiveness of nivolumab for treating metastatic renal cell carcinoma.Marterials and methods:Fifty-eight patients with metastatic renal cell carcinoma treated with nivolumab monotherapy were retrospectively studied.Patients who were treated with nivolumab as second-line therapy were included in the second-line group,while the others were included in the later-line group.The clinicopathological characteristics,effects of nivolumab,and prognoses of these groups were compared.Results:Twenty and thirty-eight patients were included in the second-line and later-line groups,respectively.There were no significant differences in the distribution of International Metastatic Renal Cell Carcinoma Database Consotium risk and other clinicopathological characteristics between the 2 groups.The proportion of patients whose objective best response was progressive disease in the second-line group was significantly lower than that in the later-line group(15%vs.50%,p=0.0090).The 50%progression-free survival with nivolumab in the second-line group was significantly better than that in the later-line group(not reached and 5 months,p=0.0018).Multivariate analysis showed that the second-line setting was an independent predictive factor for better progression-free survival(p=0.0028,hazard ratio=0.108).The 50%overall survival after starting nivolumab in the second-line and later-line groups was not reached and 27.8 months,respectively(p=0.2652).Conclusions:The therapeutic efficacy of nivolumab as second-line therapy is expected to be better than that of later therapy.

Regeneration of rat corpora cavernosa tissue by transplantation of CD133＋ cells derived from human bone marrow and placement of biodegradable gel sponge sheet

The objective is to develop an easier technique for regenerating corpora cavernosa tissue through transplantation of human bone marrow-derived CD133＋ cells into a rat corpora cavernosa defect model. We excised 2 mm× 2 mm squares of the right corpora cavernosa of twenty-three 8-week-old male nude rats. AIginate gel sponge sheets supplemented with 1 × 10^4 CD133＋ cells were then placed over the excised area of nine rats. Functional and histological evaluations were carried out 8 weeks later. The mean intracavernous pressure/mean arterial pressure ratio for the nine rats （0.34258 ± 0.0831） was significantly higher than that for eight rats with only the excision （0.0580±0.0831, P = 0.0238） and similar to that for five rats for which the penis was exposed, and there was no excision （0.37228±0.1051, P = 0.8266）. Immunohistochemical analysis revealed that the nine fully treated rats had venous sinus-like structures and quantitative reverse transcription polymerase chain reaction analysis of extracts from their alginate gel sponge sheets revealed that the amounts of mRNA encoding the nerve growth factor （NGF）, and vascular endothelial growth factor （VEGF） were significantly higher than those for rats treated with alginate gel sheets without cell supplementation （NGF： P= 0.0309; VEGF： P〈 0.0001）. These findings show that transplantation of CD133＋ cells accelerates functional and histological recovery in the corpora cavernosa defect model.