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1.
de Groot FM de Bart AC Verheijen JH Scheeren HW 《Journal of medicinal chemistry》1999,42(25):5277-5283
New prodrugs of daunorubicin and doxorubicin designed for selective activation by the serine protease plasmin are described. The low toxic prodrugs 3, 4, and 5 are converted to the corresponding cytotoxic drugs upon proteolysis by the tumor-associated protease plasmin. Application of a self-eliminating spacer was essential for enzyme activation. A prodrug containing a chloro-substituted spacer was synthesized with the aim of enhancing the rate of conversion by plasmin. All prodrugs were highly stable in buffer solution and in serum and on the average 15-fold less cytotoxic than the parent drugs in seven human tumor cell lines. A marked in vitro selectivity was demonstrated by incubation of the doxorubicin prodrugs with a plasmin generating MCF-7 breast cancer cell line transfected with urokinase-type plasminogen activator (u-PA) in comparison with the nontransfected nonplasmin generating cell line. Prodrugs 4 and 5 showed the same cytotoxic effect as the free parent drug doxorubicin in the u-PA transfected cells, indicating complete conversion of the prodrug by plasmin. Addition of the plasmin inhibitor Trasylol drastically increased the ID(50) values in the u-PA transfected MCF-7 cells for both prodrugs 4 and 5. 相似文献
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Anke M. Scheeren Hans M. Koot Sander Begeer 《Journal of autism and developmental disorders》2012,42(10):2046-2055
Qualitative differences in social interaction style exist within the autism spectrum. In this study we examined whether these differences are associated with (1) the severity of autistic symptoms and comorbid disruptive behavior problems, (2) the child’s psycho-social health, and (3) executive functioning and perspective taking skills. The social interaction style of 156 children and adolescents (6–19?years) with high-functioning autism spectrum disorder (HFASD) was determined with the Wing Subgroups Questionnaire. An active-but-odd social interaction style was positively associated with symptoms of autism, attention deficit and hyperactivity. Furthermore, an active-but-odd social interaction style was negatively associated with children’s psycho-social health and positively with executive functioning problems. Social interaction style explains part of the heterogeneity among children with HFASD. 相似文献
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Patient satisfaction and complication rate after mastectomy with immediate two‐stage breast reconstruction as compared to mastectomy without immediate breast reconstruction
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Willingham SB Volkmer JP Gentles AJ Sahoo D Dalerba P Mitra SS Wang J Contreras-Trujillo H Martin R Cohen JD Lovelace P Scheeren FA Chao MP Weiskopf K Tang C Volkmer AK Naik TJ Storm TA Mosley AR Edris B Schmid SM Sun CK Chua MS Murillo O Rajendran P Cha AC Chin RK Kim D Adorno M Raveh T Tseng D Jaiswal S Enger PØ Steinberg GK Li G So SK Majeti R Harsh GR van de Rijn M Teng NN Sunwoo JB Alizadeh AA Clarke MF Weissman IL 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(17):6662-6667
CD47, a "don't eat me" signal for phagocytic cells, is expressed on the surface of all human solid tumor cells. Analysis of patient tumor and matched adjacent normal (nontumor) tissue revealed that CD47 is overexpressed on cancer cells. CD47 mRNA expression levels correlated with a decreased probability of survival for multiple types of cancer. CD47 is a ligand for SIRPα, a protein expressed on macrophages and dendritic cells. In vitro, blockade of CD47 signaling using targeted monoclonal antibodies enabled macrophage phagocytosis of tumor cells that were otherwise protected. Administration of anti-CD47 antibodies inhibited tumor growth in orthotopic immunodeficient mouse xenotransplantation models established with patient tumor cells and increased the survival of the mice over time. Anti-CD47 antibody therapy initiated on larger tumors inhibited tumor growth and prevented or treated metastasis, but initiation of the therapy on smaller tumors was potentially curative. The safety and efficacy of targeting CD47 was further tested and validated in immune competent hosts using an orthotopic mouse breast cancer model. These results suggest all human solid tumor cells require CD47 expression to suppress phagocytic innate immune surveillance and elimination. These data, taken together with similar findings with other human neoplasms, show that CD47 is a commonly expressed molecule on all cancers, its function to block phagocytosis is known, and blockade of its function leads to tumor cell phagocytosis and elimination. CD47 is therefore a validated target for cancer therapies. 相似文献
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Rafaella Stradiotto Bernardelli Eduardo Mendonça Scheeren Alonso Romero Fuentes Filho Paty Aparecida Pereira Munir Antonio Gariba Auristela Duarte de Lima Moser Gerson Linck Bichinho 《Journal of bodywork and movement therapies》2019,23(3):508-514
Purpose: to identify postural balance changes in subjects with low back pain after the application of Kinesio Taping, which is then compared to a no treatment control group, using baropodometric evaluation. Methods: This randomized controlled trial was carried out on 50 individuals (both sexes) with chronic low back pain. They were then randomized into two groups: an experimental group - EG (treated with Kinesio Taping in the lumbar region) and a control group - CG (no intervention). Both groups underwent a baropodometric evaluation (mean plantar pressure, peak plantar pressure, plantar surface, mass distribution on right foot and left foot, mass distribution on forefoot and rear foot and base width) at four different moments: pre-intervention, 10 minutes, 48 hours, and 10 days after the intervention on the EG. The level of statistical significance was established at 5%. Results: Significant changes were observed in the EG compared to the CG. In the EG, peak pressure reduced on both right and left foot after Kinesio Taping application; the right base width was reduced, and the mass distribution between the forefoot and the rear foot normalized towards the ideal 50% distribution. These changes happened 48 hours after the Kinesio Taping application, with effects lasting up to 10 days. Conclusion: The use of Kinesio Taping in the lumbar region of subjects with chronic low back pain improved postural balance. This is proved by changes in peak plantar pressure, plantar surface, and mass distribution 48 h after Kinesio Taping application, with effects lasting up to 10 days. 相似文献
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Objective: To assess the accuracy and reproducibility of long-term implanted ultrasound transit-time flow probes for measuring cardiac
output. Design: Prospective animal study. Settings: Animal research laboratory in a university department. Animals: Eleven anaesthetised dogs, 24–34 kg. Measurements and results: Flow probes (16–24 mm S-series, Transonic) were implanted around the pulmonary artery for a mean duration of 22 months (range
6–47 months). Comparisons (n = 147) were made between cardiac output thus obtained and that measured by the direct Fick principle using oxygen uptake
(Deltatrac II Metabolic Monitor) and the arterial to mixed venous oxygen content difference measured by a galvanic cell (Lex-O2-Con-TL). Measurements were made either during baseline conditions or during pharmacologically altered cardiac output (range
22–180 ml · kg–1· min–1). Regardless of the intervention, the two methods yielded the same results in half of the dogs. In the others, however, cardiac
output was underestimated by the flow probes by up to 38 % (probably because of non-perpendicular position of the probe towards
the vessel). This difference was constant for the whole range of cardiac output studied and remained constant over the entire
observation period for each individual dog, so that a correction factor was used. Thereafter, the mean difference between
the two methods was –1.1 ml · kg–1· min–1 with a precision (SD) of 14.2 ml · kg–1· min–1 for all experiments. Conclusions: After in vivo calibration, ultrasound transit-time flow probes measure cardiac output precisely for several years, regardless
of the intervention.
Received: 1 October 1999 Final revision received: 6 January 2000 Accepted: 4 February 2000 相似文献