Search

Objectives: We conducted a phase II trial to prospectively evaluate the efficacy and safety of bortezomib-cyclophosphamide-dexamethasone (VCD) induction, autologous stem cell transplantation (ASCT), VCD consolidation, and bortezomib maintenance in transplant-eligible newly diagnosed multiple myeloma (NDMM) patients in Japan (UMIN000010542)., Methods: From 2013 to 2016, 42 patients with a median age of 58 (range 42-65) years with NDMM were enrolled in 15 centers. The primary endpoint was the complete response (CR) /stringent CR (sCR) rate after transplantation, and overall/progression-free survival rates were also evaluated., Results: Following induction therapy, the overall response rate was obtained in 71% of patients, including a CR/sCR of 10% and a very good partial response (VGPR) of 26%. Twenty-six of the 42 patients completed ASCT following the protocol and CR/sCR and VGPR rate 100 days after ASCT was 26% and 17%, respectively. During consolidation therapy, 3 of the 24 patients achieved deeper responses. Eight of the 18 patients completed 2-year bortezomib maintenance without disease progression and grade 3/4 toxicities. Five patients were VGPR or partial response after ASCT but maintained response with 2-year bortezomib maintenance. Two-year overall and progression-free survival rates were 92.5% (95% confidence interval [CI]: 78.5%-97.5%) and 62.6% (95% CI: 45.8%-75.5%), respectively. Grade 3/4 toxicities (≥ 10%) included neutropenia (19%) and anemia (17%) in induction, and thrombocytopenia (29%) in consolidation., Conclusion: VCD induction/consolidation and bortezomib maintenance with ASCT for NDMM resulted in a high CR/sCR rate and provided good overall/progression-free survival in Japan.

Objective: Retrograde neuronal cell death does not occur in mature motoneurons following the axonal injury of peripheral nerves. However, a previous study suggested that retrograde neuronal cell death does occur in adult rats after the creation of double lesions on the hypoglossal (XII) nerve based on a substantial decrease in the number of XII neurons. Using stereological methods, we examined neuronal apoptosis in XII neurons and the total number of XII neurons following repeated crush injuries to the XII nerve., Methods: The right XII nerve of adult rats was crushed three times at one-week intervals with a brain aneurysm clip. At 4 weeks after the final crush, the total numbers of XII neurons on the injured right and uninjured left sides were estimated stereologically., Results: After repeated crush injuries, no apoptosis was evident in XII neurons as indicated by immunostaining for cleaved caspase-3. Moreover, immunohistochemistry for the vesicular acetylcholine transporter revealed axonal elongation in the tongue 4 weeks after repeated crush injuries. At 4 weeks, the total numbers of XII neurons were 7800 ± 290 on the injured right side and 8000 ± 230 on the uninjured left side, and no significant difference was evident between the injured and uninjured sides., Conclusion: Neuronal cell death does not occur in XII neurons and the total number of XII neurons does not decrease after repeated crush injuries of the XII nerve in adult rats.

Objectives: The present study was conducted to examine whether repeated crush injuries have significant effects on motor functional recovery of peripheral nerves., Methods: Repeated crush injuries of the sciatic nerve were inflicted on adult rats at 1-week intervals, and functionality of the sciatic nerve was assessed by the static sciatic index each week for 8 weeks after the final injury. To determine the effects of repeated crush injuries on motor functional recovery of the sciatic nerve, tibialis anterior muscle fibers from single and triple crush injuries were examined, and fiber size and fiber reinnervation during the 2- to 4-week period after the final injury were measured., Results: Compared to single crush injuries, which completely recovered by post-injury week 4, double crush injuries resulted in retarded, but complete recovery by post-injury week 6, whereas triple crush injuries resulted in marked retardation in the regenerative process with incomplete recovery during week 8 of the experimental period. Muscle fiber size for rats with triple crush did not recover to normal range at post-injury week 4, despite its normal size for rats with single crush. The rate of reinnervation increased prominently between post-injury weeks 2 and 3 in both injuries, but the rate with triple crush was lower than that with single crush at post-injury week 3., Discussion: These results, which contradict those of a previous study that reported early functional recovery, indicate that repeated crush injuries inhibit motor functional recovery of the damaged sciatic nerve, as evidenced by delayed and incomplete regeneration, atrophied muscle fibers, and delayed reinnervation.

The neurotrophic effect of hepatocyte growth factor (HGF) on axotomized facial motor neurons was examined after local application of HGF to the proximal facial nerve stump of the neonatal rat on post-natal day one (P1). Motor neuron survival was expressed as the neuronal cell count on the injured side as a percentage of that on the noninjured side. Motor neuron survival of the control group was 76% on P3, 54% on P5 and 23% on P8, that of the HGF-treated group 78% on P3, 69% on P5 and 31% on P8, and that of the brain-derived neurotrophic factor (BDNF)-treated group 91% on P5 and 45% on P8. The motor neuron survival rates were then adjusted by deducting the facial motor neurons corresponding to the uninjured retroauricular branch (20%) of the facial nerve. The adjusted values were 70% (P3), 42% (P5) and 4% (P8) for the control group, 72% (P3), 61% (P5) and 14% (P8) for the HGF-treated group, and 88% (P5) and 32% (P8) for the BDNF-treated group. These findings demonstrate that HGF has a neuroprotective effect on injured facial motor neurons and suggest that HGF has neurotrophic properties distinct from those of BDNF.

It is well established that olfactory receptor cells are replaced during life. Periglomerular (PG) cells of the olfactory bulb have recently been demonstrated to be produced following proliferation and migration of periventricular neuronal precursor cells even in adulthood. The purpose of the present study was to examine the fate of newly formed PG cells in adult rodents. Using 5-bromodeoxyuridine (BrdU), we carried out a quantitative immunohistochemical analysis of BrdU-positive cells in the bulbar glomerular layer at different survival periods. Each number of BrdU-positive PG cells per 100 olfactory glomeruli was 34.1 +/- 3.3 (1 week), 57.2 +/- 2.7 (2 weeks), 28.0 +/- 4.7 (4 weeks) and 25.9 +/- 1.6 (8 weeks). These results indicate that bulbar PG cells, similar to olfactory receptor cells, are mostly replaced during life, and that the olfactory system is composed of disposable neuronal networks centrally as well as peripherally.