Human γδ T cells can recognize and kill non-small cell lung cancer (NSCLC) cells using the Vγ9Vδ2 T-cell receptor and/or NKG2D. We have established clinical grade large-scale ex vivo expansion of γδ T cells from peripheral blood mononuclear cells by culturing with zoledronate and interleukin-2 (IL-2). A phase I study was conducted to evaluate safety and potential antitumor effects of re-infusing ex vivo expanded γδ T cells in patients with recurrent or advanced NSCLC. Patient's peripheral blood mononuclear cells were stimulated with zoledronate (5 μM) and IL-2 (1000 IU/mL) for 14 days. Harvested cells, mostly γδ T cells, were given intravenously every 2 weeks without additional IL-2, a total of 6 times. The cumulative number of transferred γδ T cells ranged from 2.6 to 45.1 x 10⁹ (median, 15.7×10⁹). Fifteen patients underwent adoptive immunotherapy with these γδ T cells. There were no severe adverse events related to the therapy. Immunomonitoring data showed that with increasing numbers of infusions, the number of peripheral γδ T cells gradually increased. All patients remained alive during the study period with a median survival of 589 days and median progression-free survival of 126 days. According to the Response Evaluation Criteria In Solid Tumors, there were no objective responses. Six patients had stable disease, whereas the remaining 6 evaluable patients experienced progressive disease 4 weeks after the sixth transfer. We conclude that adoptive transfer of zoledronate-expanded γδ T cells is safe and feasible in patients with NSCLC, refractory to other treatments.
Duchenne muscular dystrophy (DMD) is an X-linked, lethal muscular disorder caused by a defect in the DMD gene. AAV vector-mediated micro-dystrophin cDNA transfer is an attractive approach to treatment of DMD. To establish effective gene transfer into skeletal muscle, we examined the transduction efficiency of an AAV vector in skeletal muscles of dystrophin-deficient mdx mice. When an AAV vector encoding the LacZ gene driven by a CMV promoter (AAVCMVLacZ) was introduced, -galactosidase expression markedly decreased in mdx muscle 4 weeks after injection due to immune responses against the transgene product.We also injected AAV-CMVLacZ into skeletal muscles of mini-dystrophin-transgenic mdx mice (CVBA3'), which show ameliorated phenotypes without overt signs of muscle
Duchenne muscular dystrophy (DMD) is a lethal disorder of skeletal muscle caused by mutations in the dystrophin gene. Adeno-associated virus (AAV) vector-mediated gene therapy is a promising approach to the disease. Although a rod-truncated microdystrophin gene has been proven to ameliorate dystrophic phenotypes, the level of microdystrophin expression required for effective gene therapy by an AAV vector has not been determined yet. Here, we constructed a recombinant AAV type 2 vector, AAV2-MCKDeltaCS1, expressing microdystrophin (DeltaCS1) under the control of a muscle-specific MCK promoter and injected it into TA muscles of 10-day-old and 5-week-old mdx mice. AAV2-MCKDeltaCS1-mediated gene transfer into 5-week-old mdx muscle resulted in extensive and long-term expression of microdystrophin and significantly improved force generation. Interestingly, 10-day-old injected muscle expressed microdystrophin in a limited number of myofibers but showed hypertrophy of microdystrophin-positive muscle fibers and considerable recovery of contractile force. Thus, we concluded that AAV2-MCKDeltaCS1 could be a powerful tool for gene therapy of DMD.
Pulmonary metastasectomy for HCC in selected patients resulted in relatively good outcomes with regard to OS. History of recurrence and serum DCP levels were shown to be candidates of prognostic factors for OS.
BackgroundFall-related efficacy has been found to be associated with both falls and fall risk factors such as physical performance. The aim of the present study was to clarify whether fall-related efficacy is, independent of physical performance and other potential risk factors, associated with future falls in community-dwelling older people.MethodsThe study participants were 237 Japanese older people aged 65 years and over who were living independently in their community. Fall-related efficacy and physical performance were assessed at baseline using the short version of the Falls Efficacy Scale-International (short FES-I) and 5-m walking time, the Timed Up and Go Test, the 5 Times Sit to Stand Test, and grip strength. Physical performance was then again assessed at 1-year follow-up. The number of falls was obtained every 6 months for 1 year after the baseline survey. Instrumental activities of daily living (IADL), depression, fall history, current medications, medical history, and pain were also investigated as potential confounding factors that have possible associations with falls. The associations between the short FES-I, physical performance, and number of falls were analyzed using Poisson regression analysis adjusted for physical performance and potential confounding factors.ResultsThe mean age of the participants (75.9% women) was 71.1 ± 4.6 years, and 92.8% could perform IADL independently. The total numbers of falls and fallers during the 1-year follow-up period were 70 and 42, respectively. On Poisson regression analysis adjusted for walking time and potential confounding factors, independent of physical performance, the short FES-I was found to be significantly associated with number of falls (relative risk = 1.09, p < 0.05). On the other hand, physical performance was not significantly associated with the number of falls.ConclusionsThe findings of the present study suggest that the short FES-I, independent of physical performance and other potential risk factors, is a useful index to detect fall risk in community-dwelling older people, and that fall-related efficacy is an important factor in terms of fall prevention.
Type B3 classified by the WHO histological classification system is a poor prognostic factor for survival of thymoma after extended thymectomy. Association with MG is possibly an indicator of poor survival. Age is an independent prognostic factor, suggesting favourable prognosis of thymoma after surgical treatment. Considering thymoma is a rare tumour, it would be necessary to build a multi-institutional database as soon as possible.
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