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排序方式: 共有58条查询结果,搜索用时 17 毫秒
1.
Elad Hadad Safra Rudnick-Glick Igor Grinberg Ronen Yehuda Shlomo Margel 《RSC advances》2020,10(57):34364
Proteinoids are non-toxic biodegradable polymers based on thermal step-growth polymerization of natural or synthetic amino acids. Hollow proteinoid nanoparticles (NPs) may then be formed via a self-assembly process of the proteinoid polymers in an aqueous solution. In the present article polymers and NPs based on d-arginine, glycine and l-aspartic acid, poly(RDGD), were synthesized for tumor targeting, particularly due to the high affinity of the RGD motif to areas of angiogenesis. Near IR fluorescent P(RDGD) NPs were prepared by encapsulating the fluorescent NIR dye indocyanine green (ICG) within the formed P(RDGD) NPs. Here, we investigate the effect of the covalent conjugation of polyethylene glycol (PEG), with different molecular weights, to the surface of the near IR encapsulated P(RDGD) NPs on the release of the dye to human serum due to bio-degradation of the proteinoid NPs and on the uptake by tumors. This work illustrates that the release of the encapsulated ICG from the non-PEGylated NPs is significantly faster than for that observed for the PEGylated NPs, and that the higher molecular weight is the bound PEG spacer the slower is the dye release profile. In addition, in a chicken embryo model, the non-PEGylated ICG-encapsulated P(RDGD) NPs exhibited a higher uptake in the tumor region in comparison to the PEGylated ICG-encapsulated P(RDGD) NPs. However, in a tumor xenograft mouse model, which enables a prolonged experiment, the importance of the PEG is clearly noticeable, when a high concentration of PEGylated P(RDGD) NPs was accumulated in the area of the tumor compared to the non-PEGylated P(RDGD). Moreover, the length of the PEG chain plays a major role in the ability to target the tumor. Hence, we can conclude that selectivity towards the tumor area of non-PEGylated and the PEGylated ICG-encapsulated P(RDGD) NPs can be utilized for targeting to areas of angiogenesis, such as in the cases of tumors, wounds or cuts, etc.Synthesis of NIR/ICG PEGylated poly(RDGD) proteinoid NPs and their drug delivery towards mCherry-labeled 4T1 tumor. 相似文献
2.
Expression of the insulin-like growth factors and their receptors in adenocarcinoma of the colon 总被引:12,自引:1,他引:12
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Freier S Weiss O Eran M Flyvbjerg A Dahan R Nephesh I Safra T Shiloni E Raz I 《Gut》1999,44(5):704-708
AIMS: To study changes in the expression of insulin-like growth factors (IGFs) and their receptors, as well as production of the IGF-I and IGF-II polypeptides, in adenocarcinoma of the colon. METHODS: Malignant tissue obtained at operation was used. Total RNA was extracted and specific IGF-I and IGF-II and their receptor mRNAs were measured by a solution hybridisation RNase protection assay. IGF-I and IGF-II polypeptides were measured by specific immunoassays. RESULTS: All normal tissues expressed IGF-II, IGF-I receptor, and IGF-II/mannose-6-phosphate (Man-6-P) receptor. IGF-I mRNA could not be detected but the polypeptide was present in small but equal amounts in normal and malignant tissue. IGF-II was expressed 40 times more abundantly in colonic tumours than in adjacent normal tissue and the concentration of the corresponding polypeptide was twice as high in the malignant tissue. IGF-I receptor expression was increased by a factor of 2.5 and IGF-II/Man-6-P receptor by a factor of 4. CONCLUSIONS: This study confirms that in adenocarcinoma of the human colon there is increased expression of IGF-I receptor and IGF-II. Furthermore, IGF-II/Man-6-P receptor message is increased and the increase in IGF-II message is accompanied by a doubling of the IGF-II protein in the tumour tissue compared with the adjacent normal tissue. These findings suggest that the IGF-II/Man-6-P receptor may also be involved in development of adenocarcinoma of the colon. There is rapidly accumulating evidence implicating the IGF system in the development of malignancy of the large bowel. 相似文献
3.
Safra T 《The oncologist》2003,8(Z2):17-24
Anthracyclines have demonstrated antitumor activity in a variety of cancers; however, irreversible cardiac damage is a major dose-limiting toxicity, restricting lifetime cumulative dose. The most successful strategy to improve the cardiac safety of anthracyclines to date involves liposomal encapsulation, which alters the tissue distribution and pharmacokinetics of these agents. The cardiac safeties of liposomal daunorubicin, liposomal doxorubicin (D-99), and pegylated liposomal doxorubicin have been studied in several clinical trials. The lack of published data comparing liposomal daunorubicin with conventional daunorubicin makes it difficult to draw meaningful conclusions regarding the relative cardiac safeties of these formulations. Studies indicate that the risk of anthracycline-induced cardiotoxicity is considerably lower with liposomal doxorubicin formulations than with conventional doxorubicin. Pegylated liposomal doxorubicin has been studied most extensively and has demonstrated the most significant reductions in risk for cardiotoxicity. Compared with conventional doxorubicin, pegylated liposomal doxorubicin has shown similar efficacy with a significantly lower incidence of cardiotoxicity and significantly fewer cardiac events. Although the long-term cardiac safety of these agents is unknown, data suggest that liposomal anthracyclines, particularly pegylated liposomal doxorubicin, may offer a significant clinical benefit for patients with higher risks for anthracycline-induced cardiotoxicity. 相似文献
4.
Treatment of patients with ovarian carcinoma with pegylated liposomal doxorubicin: analysis of toxicities and predictors of outcome 总被引:4,自引:0,他引:4
Safra T Groshen S Jeffers S Tsao-Wei DD Zhou L Muderspach L Roman L Morrow CP Burnett A Muggia FM 《Cancer》2001,91(1):90-100
BACKGROUND: Pegylated liposomal doxorubicin is a new formulation with activity against epithelial ovarian carcinoma (EOC). The authors sought to determine patient characteristics that may predict for response to this treatment and favorable time to failure as well as survival. METHODS: Eight patients in a Phase I study and 44 patients in two consecutive Phase II studies who were treated with pegylated liposomal doxorubicin (40-60 mg/m2 every 3 weeks for the first two cycles and 40 mg/m2 every 4 weeks thereafter) after failing initial platinum-based chemotherapies for ovarian carcinoma were analyzed. Associations were sought for response, time to failure (TTF), and survival after the treatment and various pretreatment characteristics. RESULTS: Treatment with pegylated liposomal doxorubicin yielded 23% objective responses in measurable disease and 31% overall responses, including serum CA 125-defined responses. The median TTF was 5.2 months (95% confidence interval, 4.1-6.9 months) in all patients, and the median response duration in all responders was 13.2 months (95% confidence interval, 11.9-18.5 months). The overall median survival was 15 months (95% confidence interval, 11-40 months). The main predictive factors were tumor size and baseline hemoglobin level for TTF, and these plus Karnofsky performance status were the main predictive factors for survival. CONCLUSIONS: Pegylated liposomal doxorubicin is an effective drug when it is given as secondary therapy to patients with EOC. Lack of bulky disease is the major predictor for a favorable response, TTF, and survival. The role of this treatment in combination with other effective drugs should be explored in both previously treated and untreated patients with ovarian carcinoma. 相似文献
5.
Tamar Safra Barliz Waissengrin Talya Levy Ellie Leidner Rotem Merose Diana Matceyevsky Dan Grisaru Ido Laskov Nadav Mishaan Rotem Shayzaf Ido Wolf 《The oncologist》2021,26(1):30-39
BackgroundConventional first‐line combination therapy for ovarian cancer comprises 6 cycles of adjuvant or neoadjuvant carboplatin (AUC5‐6) with paclitaxel (175 mg/m2) every 3 weeks (PC‐3W). Weekly scheduling of paclitaxel may maximize its antiangiogenic effect and reduce adverse effects. We compared the efficacy and safety of PC‐3W with a modified protocol of weekly paclitaxel 80 mg/m2 and weekly carboplatin AUC2 administered on days 1, 8, and 15 in a 28‐day cycle (i.e., with 1 week off‐treatment [PC‐W]).Materials and MethodsMedical records of consecutive patients treated between 2000 and 2018 were reviewed; 707 patients were analyzed for demographic and clinical characteristics, effectiveness and toxicity.ResultsPC‐3W was administered to 402 patients (median age, 60.5 years) and PC‐W to 305 patients (median age, 62.5 years). Most patients (91.4%) were diagnosed at stage III–IV. Notwithstanding a higher proportion of residual disease and older patients in the PC‐W group, median progression‐free survival was 21.4 months and 13.2 months for PC‐W and PC‐3W, respectively; median overall survival was 75.2 and 54.0 months for PC‐W and PC‐3W, respectively. Cox proportional hazards model indicated improved survival for patients treated with PC‐W (hazard ratio, 0.54). Similar results were observed for older patients diagnosed at ≥75 years. PC‐W demonstrated a better safety profile, with lower incidence of neuropathy, neutropenia, and alopecia.ConclusionPC‐W is as active and better tolerated than the standard PC‐3W regimen. PC‐W may serve as an alternative option for elderly or frail patients.Implications for PracticeWeekly scheduling of paclitaxel 80 mg/m2 and carboplatin AUC2, administered on days 1, 8, and 15 in a 28‐day cycle (PC‐W) for first‐line therapy for advanced ovarian cancer, is as active and better tolerated than the standard regimen of carboplatin and paclitaxel (175 mg/m2) every 3 weeks (PC‐3W). It is possible that the weekly holiday on day 21 in the PC‐W regimen may ensure better completion rates (which may result in treatment delays for toxicity in PC‐3W). The results of this retrospective analysis highlight the weekly regimen as a valid treatment option, especially for elderly patients and those with significant comorbidities. 相似文献
6.
Three recent case reports have suggested an association between failed intrauterine device (IUD) contraception and limb reduction deformities in the resulting offspring. To clarify further the purported teratogenic role of the IUD in the etiology of these defects, we conducted a case-control study of 96 mothers who had given birth to infants with limb defects. Interview data about IUD exposure at conception among these mothers were compared with interview data from 2 sets of controls: (1) 915 mothers of infants with other major defects and (2) a subset of the first group consisting of 169 mothers with chromosomally defective infants. No significant increase in the incidence of IUD use was found for cases when compared with either control group. Estimates of the relative risk were 1.28 (95% confidence limits [CL]of 0.29 to 5.67) and 1.78 (95% CL of 0.25 to 12.82) when the first and second groups of controls were used, respectively. These risk figures were not significantly different from 1.0. The evidence accumulated thus far militates against a teratogenic role for the IUD. 相似文献
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9.
Safra J Pospísilová M Kavalírová A 《Journal of pharmaceutical and biomedical analysis》2006,41(3):1022-1024
Eight phenolic acids were analyzed by capillary zone electrophoresis. On-line analyte preconcentration was carried out by hydrodynamic injection of large volume of sample followed by removal of the bulk of the low conductivity sample matrix by polarity switching. The optimal electrolyte system consisted of 50mM sodium tetraborate of pH 9.0 (adjusted with 0.1 M phosphoric acid) containing 2% of alpha-cyclodextrin. The separations were carried out with a fused silica capillary (effective length 50 cm, i.d. 50 microm) and monitored at 200 nm. Under optimized preconcentration conditions (sample injection 99 s at 100 mbar and the polarity switching time 1.0 min) linear calibration ranges (0.1-2.0 microg/ml, R=0.9979-0.9995), favourable limits of detection (0.01-0.025 microg/ml) and good repeatability of the peak areas (R.S.D.: 2.76-5.69%, n=6) were achieved. 相似文献
10.