Other Novel Targeted Therapies in Lung Cancer
Kishan J. Pandya, Julie R. Brahmer, Manuel Hidalgo in Lung Cancer, 2016
For SCLC, most promising of the small molecules still in preclinical development is ABT737 (65). ABT737 is an inhibitor of the antiapoptotic proteins Bcl-2, Bcl-xL, and Bcl-w, which was discovered using nuclear magnetic resonance-based screening and structure-based design (65). Two chemical compounds binding to sites at the hydrophobic pocket on Bcl-xL were identified and then chemically joined. The resultant molecule was modified to improve affinity for the binding site and decrease nonspecific binding to human albumin. ABT737 displays a two- to threefold order of magnitude greater binding affinity (Ki < 1 nM) than previously described Bcl-2–binding molecules. Similar to Bad, ABT737 binds and inhibits antiapoptotic Bcl-2 family proteins but does not directly activate the proapoptotic proteins, Bax and Bak (65). ABT737 alone caused complete regression of established SCLC tumor xenografts and shows synergy with chemotherapy and radiation in various tumor cell lines including NSCLC. The drug was well tolerated with minor hematologic toxicity. These preclinical data suggest that ABT737 may be effective for the treatment of SCLC and may enhance the efficacy of chemotherapy and radiation in NSCLC.
Polyenes for prevention and treatment of invasive fungal infections
Mahmoud A. Ghannoum, John R. Perfect in Antifungal Therapy, 2019
The rate of infusion may also impact toxicity. Therefore, rapid infusions should be avoided [272]. Despite pharmacodynamic studies that illustrate the concentration-dependent nature of AmBd’s fungicidal activity [14,50], continuous infusion of the daily dose over 24 hours as a strategy to reduce nephrotoxicity has been investigated [142,143,273,274]. For AmBd, continuous infusion has decreased infusion-related reactions, nephrotoxicity, and mortality relative to a 4-hours infusion [142]. Other open-labeled trials have also documented the reductions in nephrotoxicity [143]. It is unknown, however, whether such data applies to LBFAmB, since these preparations were not studied. Models accounting for human serum albumin fail to show significant pharmacodyanmic differences between methods of administration [14]. In addition, such a method of administration cannot be recommended due to lack of efficacy data in patients with documented infections.
Culture systems for the human embryo
David K. Gardner, Ariel Weissman, Colin M. Howles, Zeev Shoham in Textbook of Assisted Reproductive Techniques, 2017
To this end, recombinant human albumin is available, which eliminates the problems inherent with using blood-derived products and can lead to the standardization of media formulations. Recombinant human albumin has now been shown to be as effective as bloodderived albumin in supporting fertilization (116) and embryo development, and its efficacy has been proven in a prospective randomized trial (117). Significantly, embryos cultured in the presence of recombinant albumin exhibit an increased tolerance to cryopreservation (118). Historically, its clinical use has been restricted by price; however, with costs of such recombinant products falling, it makes this an appropriate time to re-evaluate its clinical use.
Shedding light on experimental intra-articular drugs for treating knee osteoarthritis
Published in Expert Opinion on Investigational Drugs, 2023
Yang Zhao, Qianhua Ou, Yu Cai, Guangfeng Ruan, Yan Zhang, Changhai Ding
Human serum albumin has long been safely administered as a 5% solution in treatment for shock, burns, and plasma volume expansion [127]. The low molecular weight fraction of 5% human serum albumin (LMWF −5A), with aspartyl-alanyl diketopiperazine considered as its active component, has been shown to have multiple anti-inflammatory and immune modulating effects [52,128]. In the context of KOA, LMWF − 5A is reported to trigger anti-inflammatory signaling in synovial fibroblasts, and this may be a primary component of its therapeutic mode of action in relieving OA pain [53]. Despite the unclear preclinical evidence, it has been investigated as an IA drug for pain control. A phase 2 clinical trial demonstrated that a single IA injection of LMWF − 5A was safe and effective in improving the pain of moderate to severe KOA over 12 weeks [54]. More recently, a study investigated the safety and efficacy of multiple (3 biweekly) IA injections of LMWF − 5A in KOA and reported that repeated IA injections of LMWF − 5A are safe and are effective in relieving pain in KOA through 20 weeks [55]. Considering the lack of highly acknowledged results and underlying mechanism of LMWF − 5A, we still need more rigorous evidence to properly assess its therapeutic potential.
Resveratrol loaded glycyrrhizic acid-conjugated human serum albumin nanoparticles for tail vein injection II: pharmacokinetics, tissue distribution and bioavailability
Published in Drug Delivery, 2020
Mingfang Wu, Chen Zhong, Yiping Deng, Qian Zhang, Xiaoxue Zhang, Xiuhua Zhao
In recent years, nano-carriers have significant advantages in anticancer drug delivery system (DDSs). It can enhance the high permeability and retention effect of the drug in solid tumor and improve the circulation time in the blood. In addition, multi-functional nano-carriers can endow them with targeting function and improve the selective uptake efficiency of cells (Moros et al., 2013; Wang et al., 2016; Yin et al., 2017; Wang et al., 2018). Human serum albumin (HSA) is a kind of human-derived substance, which has the characteristics of non-toxicity, non-immunogenicity and good biocompatibility (Kratz, 2008). Human serum albumin exists in a large number of human blood, has excellent water solubility and safety, and has been widely used as a multifunctional drug delivery carrier (Deng et al., 2018; Hoonjan et al., 2018). In addition, the functional groups such as carboxyl and amino groups on the surface of albumin are beneficial to the surface functionalization of albumin nanoparticles (Mo et al., 2007; Yu et al., 2014). Drugs that use human serum albumin as a carrier can enhance the dissolution rate and saturation solubility of drugs by intravenous injection. Cumulative data show that when the poorly hydrophilic drug binds to human serum albumin, the bioavailability of the drug can be increased (Kumar et al., 2013; Taneja & Singh, 2017).
Effect of intraoperative dexmedetomidine on renal function after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: a randomized, placebo-controlled trial
Published in International Journal of Hyperthermia, 2019
Young Song, Do-Hyeong Kim, Tae Dong Kwon, Dong Woo Han, Seung Hyuk Baik, Hwan Ho Jung, Ji Young Kim
Hemodynamic monitoring included the cardiac index (CI) and stroke volume variation (SVV) derived from the VigileoTM System (Edwards Lifesciences, Irvine, CA) and central venous pressure (CVP) obtained from the internal jugular vein. Anesthesia was maintained with sevoflurane inhalation and remifentanil infusion. Mean arterial pressure (MAP) was maintained between 60 and 80 mmHg with adequate fluid resuscitation and the use of norepinephrine. Goal-directed fluid therapy was performed under the guidance of SVV with concomitant consideration of preoperative deficit, maintenance and surgical loss. Balanced crystalloid (Plasma Solution A Inj.; CJ Pharma, Seoul, Korea) was administered as a primary resuscitation fluid and balanced synthetic colloid (Volulyte; Fresenius Kabi, Bad Homburg, Germany) was administered up to 1000 ml to compensate for blood loss. Packed red blood cells (pRBC) were transfused when the hematocrit was <25%. A 20% human albumin solution (SK chemical, Seoul, Korea) was administered to maintain serum albumin concentration at >2.0 g/dL. Active cooling with a cooling mattress forced air and infusion of cold fluids was performed during HIPEC. After surgery, all participants were transferred to the ICU with or without extubation at the attending anesthesiologist’s discretion. Postoperative care was performed by the attending physician and intensivist.