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Drug Targeting to Tumors: Principles, Pitfalls and (Pre-) Clinical Progress
Published in Lajos P. Balogh, Nano-Enabled Medical Applications, 2020
Twan Lammers, Fabian Kiessling, Wim E. Hennink, Gert Storm
To overcome this shortcoming, to better predict how well nanomedicines (and also standard chemotherapeutic drugs) will work in patients, and to thereby improve the time- and cost-effectiveness of clinical translation, it would be worthwhile to consider establishing a well-defined panel of animal models—comparable to the NCI-60 set of cancer cell lines—to test (and head-to-head compare) the efficacy of all formulations which are close to being evaluated in patients. Depending on the tumor type to be treated, such a panel could for instance include 1 representative subcutaneous xenograft model, 1 representative subcutaneous syngeneic model, 1 orthotopic model, 1 metastatic model and ideally also 1 transgenic model. By attempting to (pre-) define which rodent tumor models are representative for the clinical situation, by validating these choices via standard chemotherapeutic interventions (i.e. those which are currently used clinically), and by evaluating how well novel (nanomedicine) formulations are able to improve therapeutic outcome in such models, it should in principle be possible to much better predict how well new therapeutic entities might eventually perform in patients, to more reliably compare novel to established treatments, and to thereby substantially facilitate the time- and cost-effectiveness of clinical translation.
Radiogenomics
Published in Jun Deng, Lei Xing, Big Data in Radiation Oncology, 2019
Barry S. Rosenstein, Gaurav Pandey, Corey W. Speers, Jung Hun Oh, Catharine M.L. West, Charles S. Mayo
As noted earlier, efforts to develop a “pan-cancer” genomic signature of radiation response have been reported. In these initial studies, cell line sensitivity to ionizing radiation was evaluated across the NCI-60 panel of cancer cell lines (Torres-Roca et al. 2005; Eschrich et al. 2009). Genes associated with intrinsic radiosensitivity (measured as surviving fraction at 2 Gy, SF2) at the RNA level were then identified. Network analysis was used to identify 10 hub genes from which a radio sensitivity index (RSI) was derived. The group assessed the performance of RSI in various disease types with varying levels of success (Eschrich et al. 2009, 2012; Ahmed et al. 2015; Strom et al. 2015). Importantly, RSI was shown to predict benefit from adjuvant radiotherapy in breast cancer patients and has progressed to prospective evaluation in a clinical trial.
Selenium-mediated epigenetic regulation of selenoprotein expression in colorectal cancer
Published in Gary Bañuelos, Zhi-Qing Lin, Dongli Liang, Xue-bin Yin, Selenium Research for Environment and Human Health: Perspectives, Technologies and Advancements, 2019
Real-time RT-PCR data are presented as means ± SE and were analyzed using GraphPad Prism (v.4, La Jolla, CA, USA). Differences with p < 0.05 are considered significant. The CellMiner’s NCI-60 Analysis Tool, which integrates datasets of 60 human cancer cell lines routinely used for comparative molecular analyses (Reinhold et al. 2012), was used to compare average transcript expression patterns of genes encoding for selenoproteins and DNA methyltransferases, as well as to compare gene-specific methylation levels.
Ultrasound-assisted green synthesis of triazole-based azomethine/thiazolidin-4-one hybrid inhibitors for cancer therapy through targeting dysregulation signatures of some Rab proteins
Published in Green Chemistry Letters and Reviews, 2023
Aboubakr H. Abdelmonsef, Ahmed M. El-Saghier, Asmaa M. Kadry
Twelve compounds 1a, 1b, 3a-3d, 4a–4d, 5c, and 6c were selected by National Cancer Institute (NCI) according to the protocol of the Drug Evaluation Branch of the National Cancer Institute, Bethesda, USA, for in vitro anticancer screening (42,43). The prepared analogs were tested at single concentration of 10−5 M and the culture was incubated for 48 hours. End-point determinations were made with a protein binding dye, Sulforhodamine B (SRB). All the screened compounds reduced the growth of most cancer cell lines to 32% or less. Additionally, they are called active and subsequently passed for further evaluation toward NCI-60 human tumor cell lines derived from nine different cancers: leukemia, melanoma, lung, colon, CNS, ovarian, renal, prostate, and breast.