Cortical Regions Encoding Hardness Perception Modulated by Visual Information Identified by Functional Magnetic Resonance Imaging With Multivoxel Pattern Analysis

Recent studies have revealed that hardness perception is determined by visual information along with the haptic input. This study investigated the cortical regions involved in hardness perception modulated by visual information using functional magnetic resonance imaging (fMRI) and multivoxel pattern analysis (MVPA). Twenty-two healthy participants were enrolled. They were required to place their left and right hands at the front and back, respectively, of a mirror attached to a platform placed above them while lying in a magnetic resonance scanner. In conditions SFT, MED, and HRD, one of three polyurethane foam pads of varying hardness (soft, medium, and hard, respectively) was presented to the left hand in a given trial, while only the medium pad was presented to the right hand in all trials. MED was defined as the control condition, because the visual and haptic information was congruent. During the scan, the participants were required to push the pad with the both hands while observing the reflection of the left hand and estimate the hardness of the pad perceived by the right (hidden) hand based on magnitude estimation. Behavioral results showed that the perceived hardness was significantly biased toward softer or harder in >73% of the trials in conditions SFT and HRD; we designated these trials as visually modulated (SFTvm and HRDvm, respectively). The accuracy map was calculated individually for each of the pair-wise comparisons of (SFTvm vs. MED), (HRDvm vs. MED), and (SFTvm vs. HRDvm) by a searchlight MVPA, and the cortical regions encoding the perceived hardness with visual modulation were identified by conjunction of the three accuracy maps in group analysis. The cluster was observed in the right sensory motor cortex, left anterior intraparietal sulcus (aIPS), bilateral parietal operculum (PO), and occipito-temporal cortex (OTC). Together with previous findings on such cortical regions, we conclude that the visual information of finger movements processed in the OTC may be integrated with haptic input in the left aIPS, and the subjective hardness perceived by the right hand with visual modulation may be processed in the cortical network between the left PO and aIPS

A Phase I Trial of 100mg/m2 Docetaxel in Patients with Advanced or Recurrent Breast Cancer

Docetaxel is a standard treatment for patients with advanced or recurrent breast cancer. The recommended dose is 60 to 100 mg/m2. Previous study have shown that the tumor response rates of patients who received docetaxel monotherapy at doses of 60, 75, and 100 mg/m2 were 22.1% , 23.3% , and 36.0% , respectively, and there was a significant relationship between the dose and response. In Europe and the United States, docetaxel is approved at a dose of 100 mg/m2, and Japanese guidelines also recommend a dose of 100 mg/m2. However, the approved dose in Japan is up to 75 mg/m2. We have launched a phase I trial evaluating 100 mg/m2 docetaxel in patients with advanced or relapsed breast cancer. The major eligibility criteria are as follows: age ≥20 years, pathologically diagnosed breast cancer, recurrent or advanced breast cancer, a good performance status, and HER2 [human epidermal growth factor receptor 2] negative. The primary endpoint is demonstrated safety of 100 mg/m2 docetaxel. This study will clarify whether 100mg/m2 docetaxel can be administrated safely in Japanese patients with advanced or recurrent breast cancer

An exploratory clinical trial for idiopathic osteonecrosis of femoral head by cultured autologous multipotent mesenchymal stromal cells augmented with vascularized bone grafts.

Idiopathic osteonecrosis of femoral head (ION) is a painful disorder that progresses to collapse of the femoral head and destruction of the hip joint. Although its precise pathology remains unknown, the loss of blood supply causing the loss of living bone-forming cells is a hallmark of the pathophysiology of osteonecrosis. Transplantation of multipotent mesenchymal stromal cells (MSCs) is a promising tool for regenerating the musculoskeletal system. The aim of the present study was to assess the safety and efficacy of transplantation of cultured autologous bone marrow-derived MSCs mixed with β-tricalcium phosphate (β-TCP) in combination with vascularized bone grafts for the treatment of advanced stage ION in a clinical trial. Ten patients with stage 3 ION were enrolled in this study. Autologous bone marrow-derived MSCs were cultured with autologous serum, and cells (0.5-1.0×10(8)) were transplanted after mixing with β-TCP granules in combination with vascularized iliac bone grafts. Patients were assessed 24 months after treatment. The primary and secondary endpoints were progression of the radiological stage and changes in bone volume at the femoral head, and clinical score, respectively. Nine of ten patients completed the protocol, seven of whom remained at stage 3, and the remaining two cases progressed to stage 4. The average bone volume increased from 56.5±8.5 cm(3) to 57.7±10.6 cm(3). The average clinical score according to the Japan Orthopaedic Association improved from 65.6±25.5 points to 87.9±19.0 points. One severe adverse event was observed, which was not related to the clinical trial. Although the efficacy of cell transplantation was still to be determined, all procedures were successfully performed and some young patients with extensive necrotic lesions with pain demonstrated good bone regeneration with amelioration of symptoms. Further improvements in our method using MSCs and the proper selection of patients will open a new approach for the treatment of this refractory disease

A novel method to isolate mesenchymal stem cells from bone marrow in a closed system using a device made by nonwoven fabric.

Bone marrow stromal cells (BMSCs) include cells with multidirectional differentiation potential described as mesenchymal stem cells. For clinical use, it is important to develop a way to isolate BMSCs from bone marrow in a closed system without centrifugation. After screening 200 biomaterials, we developed a device containing a nonwoven fabric filter composed of rayon and polyethylene. The filter selectively traps BMSCs among mononuclear cells in bone marrow based on affinity, not cell size. The cells are then recovered by the retrograde flow. Using canine and human bone marrow cells, the biological properties of BMSCs isolated by the device were compared with those obtained by conventional methods using centrifugation. The total number isolated by the device was larger, as was the number of CD106(+)/STRO-1(+) double-positive cells. The cells showed osteogenic, chondrogenic, and adipogenic differentiation potential in vitro. Finally, the direct transplantation of cells isolated by the device without in vitro cultivation accelerated bone regeneration in a canine model of osteonecrosis in vivo. The proposed method is rapid and efficient, does not require a biological clean area, and will be useful for the clinical application of mesenchymal stem cells in bone marrow