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31.
MS Thakar C Bonfim BM Sandmaier P O'Donnell L Ribeiro T Gooley HJ Deeg ME Flowers R Pasquini R Storb AE Woolfrey HP Kiem 《Pediatric hematology and oncology》2012,29(6):568-578
Allogeneic hematopoietic cell transplantation (HCT) is the only known cure for patients with Fanconi anemia (FA) who develop aplasia or leukemia. However, transplant regimens typically contain high-dose alkylators, which are poorly tolerated in FA patients. Furthermore, as many patients lack human leukocyte antigen (HLA)-matched family donors, alternative donors are used, which can increase the risk of both graft rejection and graft-versus-host disease (GVHD). To improve on these three concerns, we developed a multi-institutional clinical trial using a fludarabine (FLU)-based conditioning regimen with limited alkylators/low-dose radiation, HLA-haploidentical marrow, followed by reduced-dose cyclophosphamide (CY) to treat three FA patients with aplasia. All three patients engrafted with 100% donor CD3 chimerism at 1 month. One patient died early from disseminated toxoplasmosis infection. Of the two survivors, one had significant pretransplant co-morbidities and inadequate immunosuppression, and developed severe acute GVHD. The other patient had only mild acute and no chronic GVHD. With a follow-up of 2 and 3?years, respectively, both patients are doing well, are transfusion-independent, and maintain full donor chimerism. The patient with severe GVHD has resolving oral GVHD and good quality of life. We conclude that using low-intensity conditioning, HLA-haploidentical marrow, and reduced-dose CY for in vivo T-cell depletion can correct life-threatening aplasia in FA patients. 相似文献
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Stem cell gene therapy has long been limited by low gene transfer efficiency to hematopoietic stem cells. Recent years have witnessed clinical success in select diseases such as X-linked severe combined immunodeficiency (SCID) and ADA deficiency. Arguably, the single most important factor responsible for the increased efficacy of these recent protocols is the fact that the genetic correction provided a selective in vivo survival advantage. Since, for most diseases, there will be no selective advantage of gene-corrected cells, there has been a significant effort to arm vectors with a survival advantage. Two-gene vectors can be used to introduce the therapeutic gene and a selectable marker gene. Efficient in vivo selection strategies have been demonstrated in clinically relevant large-animal models. Mutant forms of the DNA repair-enzyme methylguanine methyltransferase in particular have allowed for efficient in vivo selection and have achieved sustained marking with virtually 100% gene-modified cells in large animals, and with clinically acceptable toxicity. Translation of these strategies to the clinical setting is imminent. Here, we review how in vivo selection strategies can be used to make stem cell gene therapy applicable to the treatment of a wider scope of genetic diseases and patients. 相似文献
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Phan Van Kiem Nguyen Thi Mai Chau Van Minh Nguyen Huu Khoi Nguyen Hai Dang Nguyen Phuong Thao Nguyen Xuan Cuong Nguyen Hoai Nam Nguyen Xuan Nhiem Yvan Vander Heyden Joëlle Quetin-Leclercq Gyo Nam Kim Hae Dong Jang Young Ho Kim 《Archives of pharmacal research》2010,33(2):203-208
Two new 2-C-β-D-glucopyranosyl benzoic acid derivatives named mallonanosides A (1) and B (2) were isolated from the methanolic extract of the leaves of Mallotus nanus along with five known flavonoids, kaempferin (3), juglanin (4), quercitrin (5), myricitrin (6), and rhoifolin (7). Their structures were established on the basis of spectral and chemical evidence. Their antioxidant activities were shown to depend on the number of hydroxyl groups, and the location and species of sugar moiety. 相似文献
36.
Nguyen Huu Tung Chau Van Minh Phan Van Kiem Hoang Thanh Huong Nguyen Hoai Nam Nguyen Xuan Cuong Tran Hong Quang Nguyen Xuan Nhiem Jae-Hee Hyun Hee-Kyoung Kang Young Ho Kim 《Archives of pharmacal research》2010,33(4):503-508
Chromatographic separation resulted in the identification of one new squalene derivative, named lobophytene (1), three cembranoid diterpenes (2–4), and two sterols (5 and 6) from the Vietnamese marine soft coral Lobophytum sp. Their structures were identified on the basis of extensive spectroscopic data and comparison of those with reported data. Compounds 1 and 2 showed significant cytotoxic activities against lung (A549) and colon (HT-29) cell lines with IC50 values of 8.2 and 5.6 μM for 1; 5.1 and 1.8 μM for 2, respectively. 相似文献
37.
Psoralen and ultraviolet A irradiation (PUVA) as therapy for steroid-resistant cutaneous acute graft-versus-host disease. 总被引:2,自引:0,他引:2
Terry Furlong Wendy Leisenring Rainer Storb Claudio Anasetti Frederick R Appelbaum Paul A Carpenter H Joachim Deeg Kristine Doney Hans-Peter Kiem Richard A Nash Jean E Sanders Robert Witherspoon Dianne Thompson Paul J Martin 《Biology of blood and marrow transplantation》2002,8(4):206-212
Psoralen plus ultraviolet A irradiation (PUVA) has immunomodulatory effects and is used to treat a variety of immune-mediated dermatologic diseases. We administered PUVA to 103 patients for treatment of steroid-resistant acute graft-versus-host disease (GVHD) of the skin. Twenty-nine patients had related donors (12 HLA-mismatched) and 74 had unrelated donors (23 HLA-mismatched). The median onset of GVHD was day 13 after transplantation, and the median onset of PUVA treatment was day 46. PUVA was administered as secondary therapy for 86 patients and tertiary therapy or greater for 17 patients. The median number of treatments was 16, and the mean cumulative exposure was 41 J/cm2. PUVA was generally well tolerated with 8 patients discontinuing therapy because of toxicity. At the start of PUVA treatment, 48 patients had rash affecting >50% of their body surface area (BSA), and 91 had rash involving >25% BSA. Of 65 patients who were evaluated after 6 weeks of PUVA treatment, 11 still had rash involving >50% BSA, 24 had rash involving >25% BSA, and 24 had no rash. The mean daily dose of prednisone at the start of PUVA therapy was 1.6 mg/kg compared to 0.7 mg/kg after 6 weeks of therapy. Fifty-nine patients (57%) did not require additional therapy for skin GVHD after starting PUVA. Ninety-two percent of patients developed chronic GVHD. Fifty-three patients (51%) remain alive at 129-1883 days after transplantation. These results suggest that PUVA can be an effective therapy for steroid-resistant acute GVHD of the skin. 相似文献
38.
Tran Hong Quang Nguyen Thi Thanh Ngan Chau Van Minh Phan Van Kiem Nguyen Xuan Nhiem Bui Huu Tai Nguyen Phuong Thao Doobyeong Chae Vivek Bhakta Mathema Young-Sang Koh Je-Hyun Lee Seo Young Yang Young Ho Kim 《Archives of pharmacal research》2013,36(3):327-334
Kalopanax pictus (Araliaceae) is a deciduous tree distributed in Korea, Japan, and China. The stem bark of K. pictus has been functionally used as a traditional crude drug for the treatment of various inflammatory diseases. In the present study, we describe the inhibitory effects of oleanane-type triterpenes and saponins isolated from the stem bark of K. pictus on production of pro-inflammatory cytokines in LPS-stimulated bone marrow-derived dendritic cells. Of the compounds tested, 16,23,29-trihydroxy-3-oxo-olean-12-en-28-oic acid (1), 4,23,29-trihydroxy-3,4-seco-olean-12-en-3-oate-28-oic acid (2), 3β,6β,23-trihydroxyolean-12-en-28-oic acid 28-O-β-D-glucopyranoside (3), nipponogenin E (6), 3β,6β,23-trihydroxyolean-12-en-28-oic acid (7), and caulophyllogenin (19) significantly inhibited the production of IL-12 p40 and IL-6 with IC50 values ranging from 3.3 to 9.1 μM. Compounds 2, 3, 7, and 19 significantly suppressed the secretion of TNF-α with IC50 ranging from 8.8 to 20.0 μM. These data provide scientific support for the use of K. pictus stem bark and its triterpene and saponin components in the inhibition of pro-inflammatory cytokine secretion, including IL-12 p40, IL-6, and TNF-α, and for prevention and treatment of inflammatory diseases. 相似文献
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