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21.
Reactions of closo-1-Me-2-Iodobutyl-1,2-closo-dicarborane, 1-Me-2-I(CH2)4-C2B10H10, with l-dopa methyl ester can produce carboranyl l-dopa methyl esters in 54% yield in the presence of sodium hydroxide. The appended closo-carboranes can be decapitated with sodium hydroxide in a mixed solvent of ethanol and deionized water to produce highly water-soluble carboranyl levodopa in 64% yield. All the new compounds were characterized by 1H, 13C, 11B NMR, FT-IR spectroscopy and elemental analysis. The highly water soluble carboranyl levodopa 4 shows promising efficacy of anti-tumors in vitro in the presence of slow neutron beams. 相似文献
22.
Dennis T. Villareal Caroline M. Apovian Robert F. Kushner Samuel Klein 《Obesity (Silver Spring, Md.)》2005,13(11):1849-1863
Obesity causes serious medical complications and impairs quality of life. Moreover, in older persons, obesity can exacerbate the age‐related decline in physical function and lead to frailty. However, appropriate treatment for obesity in older persons is controversial because of the reduction in relative health risks associated with increasing body mass index and the concern that weight loss could have potential harmful effects in the older population. This joint position statement from the American Society for Nutrition and NAASO, The Obesity Society reviews the clinical issues related to obesity in older persons and provides health professionals with appropriate weight‐management guidelines for obese older patients. The current data show that weight‐loss therapy improves physical function, quality of life, and the medical complications associated with obesity in older persons. Therefore, weight‐loss therapy that minimizes muscle and bone losses is recommended for older persons who are obese and who have functional impairments or medical complications that can benefit from weight loss. 相似文献
23.
Therapeutic angiogenesis promises to aid the healing and regeneration of tissues suffering from a compromised vascular supply. Ischaemia therapy has so far primarily focused on delivering isolated angiogenic growth factors. The limited success of these strategies in clinical trials, however, is increasingly forcing researchers to recognize the difficulties associated with trying to mimic the angiogenic process, due to its natural complexity. Instead, a new school of thought is gradually emerging, focusing on how to induce angiogenesis at its onset, by utilizing hypoxia, the primary angiogenic stimulus in physiological, as well pathological states. This shift in therapeutic approach is underlined by the realization of the importance of depressed HIF-1 α-mediated gene programming in non-healing ischemic tissues, which could explain their apparent habituation to chronic hypoxic stress and the limited capacity to generate adaptive angiogenesis. Hypoxia-based strategies, then effectively aim to override the habituated angiogenic cellular response, re-start the regenerative process and drive it to completion. Here we make a distinction between those strategies that utilize hypoxia in vitro as a preconditioning tool to optimize the angiogenic potential of tissue/cells before transplantation, vs. strategies that aim to induce hypoxia-induced signaling in vivo, directly, through pharmacological means or gene transfer. We then discuss possible future directions for the field, as it moves into the phase of clinical trials. 相似文献
24.
The paper by Raptis et al. concludes that proton therapy has an advantage over photon therapy with respect to the induction of a second cancer. Furthermore, the authors conclude that physiological movements and radiobiological parameters do not affect the general trend of lower risk associated with proton therapy. The work is based on a modeling framework which is different from most previously used models on the same subject. This invited commentary puts the findings of the paper in context with other published modeling studies on second cancer risk after proton and photon radiation therapy for breast cancer. 相似文献
25.
Multidrug resistance (MDR) is a major problem in cancer chemotherapy. As P-glycoprotein is the key molecule in MDR, many investigators have constructed anti-P-glycoprotein monoclonal antibodies (MAbs). Those antibodies, including MRK16 and C219, were used for elucidation of the mechanism of MDR and for overcoming of MDR. This article describes the characterization of the antibodies against the P-glycoprotein and other proteins of multidrug-resistant tumor cells, and discusses the therapeutic implication of the antibodies.Abbreviation ADCC
antibody-dependent cell-mediated cytotoxicity 相似文献
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27.
Hasan Farajipour Susan Rahimian Mohsen Taghizadeh 《Journal of cellular biochemistry》2019,120(5):6886-6893
The retina is the neural portion and light-sensitive layer of the eye, which has been observed in most of the vertebrates. The retina is composed of light-sensitive cells that absorb light and convert it into neural signals. These signals are sent to the brain for visual recognition. It has been shown that many pathogenesis conditions, including inflammation, angiogenesis, oxidative stress, and imbalanced histone modifications in the retina are associated with initiation and progression of retinal diseases (ie, glaucoma, diabetic retinopathy, and age-related macular degeneration). Currently available treatments include laser surgery, freezing, stem-cell therapy, shrinking abnormal blood vessels. It has some limitations, such as invasive methods, high costs, and many side effects. Hence, finding a new therapeutic platform for stopping or slowing of the disease progression is required. Curcumin is a natural product, which is associated with a wide range of properties, such as antioxidant, anti-inflammatory, antiangiogenic, and antitumor activates. It exerts therapeutic effects via activation/inhibition cellular and molecular targets involved in various diseases, such as retinal diseases. Increasing evidence revealed that curcumin can be used as a therapeutic option in the treatment of different retinal diseases. Here, we summarized various clinical and preclinical studies that used curcumin as a therapeutic agent in the treatment of retinal disorders. 相似文献
28.
Kristina Wallenius Tobias Kroon Therese Hagstedt Lars Löfgren Maria Sörhede-Winzell Jeremie Boucher Daniel Lindén Nicholas D. Oakes 《Journal of lipid research》2022,63(3):100176
Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to increase ketone bodies in patients with type 2 diabetes; however, the underlying mechanisms have not been fully elucidated. Here we examined the effect of the SGLT2 inhibitor dapagliflozin (1 mg/kg/day, formulated in a water, PEG400, ethanol, propylene glycol solution, 4 weeks) on lipid metabolism in obese Zucker rats. Fasting FFA metabolism was assessed in the anesthetized state using a [9,10-3H(N)]-palmitic acid tracer by estimating rates of plasma FFA appearance (Ra), whole-body FFA oxidation (Rox), and nonoxidative disposal (Rst). In the liver, clearance (Kβ-ox) and flux (Rβ-ox) of FFA into β-oxidation were estimated using [9,10-3H]-(R)-bromopalmitate/[U-14C]palmitate tracers. As expected, dapagliflozin induced glycosuria and a robust antidiabetic effect; treatment reduced fasting plasma glucose and insulin, lowered glycated hemoglobin, and increased pancreatic insulin content compared with vehicle controls. Dapagliflozin also increased plasma FFA, Ra, Rox, and Rst with enhanced channeling toward oxidation versus storage. In the liver, there was also enhanced channeling of FFA to β-oxidation, with increased Kβ-ox, Rβ-ox and tissue acetyl-CoA, compared with controls. Finally, dapagliflozin increased hepatic HMG-CoA and plasma β-hydroxybutyrate, consistent with a specific enhancement of ketogenesis. Since ketogenesis has not been directly measured, we cannot exclude an additional contribution of impaired ketone body clearance to the ketosis. In conclusion, this study provides evidence that the dapagliflozin-induced increase in plasma ketone bodies is driven by the combined action of FFA mobilization from adipose tissue and diversion of hepatic FFA toward β-oxidation. 相似文献
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30.
Lili Guo Alexander A. Shestov Andrew J. Worth Kavindra Nath David S. Nelson Dennis B. Leeper Jerry D. Glickson Ian A. Blair 《The Journal of biological chemistry》2016,291(1):42-57
The antitumor agent lonidamine (LND; 1-(2,4-dichlorobenzyl)-1H-indazole-3-carboxylic acid) is known to interfere with energy-yielding processes in cancer cells. However, the effect of LND on central energy metabolism has never been fully characterized. In this study, we report that a significant amount of succinate is accumulated in LND-treated cells. LND inhibits the formation of fumarate and malate and suppresses succinate-induced respiration of isolated mitochondria. Utilizing biochemical assays, we determined that LND inhibits the succinate-ubiquinone reductase activity of respiratory complex II without fully blocking succinate dehydrogenase activity. LND also induces cellular reactive oxygen species through complex II, which reduced the viability of the DB-1 melanoma cell line. The ability of LND to promote cell death was potentiated by its suppression of the pentose phosphate pathway, which resulted in inhibition of NADPH and glutathione generation. Using stable isotope tracers in combination with isotopologue analysis, we showed that LND increased glutaminolysis but decreased reductive carboxylation of glutamine-derived α-ketoglutarate. Our findings on the previously uncharacterized effects of LND may provide potential combinational therapeutic approaches for targeting cancer metabolism. 相似文献