China
Africa
Explore chapters and articles related to this topic
Endocrine Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
The analogues zindoxifene, bazedoxifene, and pipendoxifene (Figure 8.10) are all based on the related 2-phenylindole ring system. Zindoxifene (formally D-16726 and NSC-341952), first described in 1984 by ASTA Medica, was the first indole-based SERN to be developed in the 1980s and 1990s for the treatment of breast cancer, although it failed to demonstrate significant efficacy toward breast cancer in the clinic, and so was not progressed. However, it served as a lead structure for this 2-phenylindole class of SERMs, and the analog bazedoxifene was derived from the major active metabolite of zindoxifene (i.e., D-15414).
Structure-Function Elucidation of Flavonoids by Modern Technologies
Published in Dilip Ghosh, Pulok K. Mukherjee, Natural Medicines, 2019
Ritu Varshney, Neeladrisingha Das, Rutusmita Mishra, Partha Roy
DAPI or 4′,6-diamidino-2-phenylindole is a florescent dye used to stain the nucleus of a cell. This stain has the property of binding to the A-T rich regions in the DNA (Eriksson et al. 1993) and the DAPI-DNA complex emits fluorescence. Most of the modern anticancer drugs focus on DNA damage, as it leads to apoptosis and other forms of cell death (Kawanishi and Kiraku 2004; Havelka et al. 2007; Cheung-Ong et al. 2013). This method is mainly used for deducing the DNA damage inside the cells by microscopic visualization. The main principle behind this assay is that the binding of DAPI to the ds-DNA produces a ~20-fold fluorescence enhancement (Barcellona et al. 1990). This is observed due to displacement of water molecules from both DNA as well as DAPI. DAPI also binds to RNA at selective A-U intercalation (Tanious et al. 1992) but the intensity of fluorescence is comparatively low compared to that of DNA. The cells treated with cytotoxic drugs will have nuclear damage (Cheung-Ong et al. 2013), and the fragmented DNA will have clusters of DAPI-DNA complexes that can be distinguished morphologically under a microscopic. Based upon the image, the quantification and a relative dosage-survival analysis can be carried out. As far as the fluorescence characteristic is concerned, the excitation and emission maximum of DAPI (bound to ds-DNA) is 358 and 461 nm, respectively. DAPI is usually excited by a UV lamp, but xenon and mercury-arc lamps can also be used for the excitation.
An Intervention Trial on Precursor Lesions for Oesophageal Cancer in a High Incidence Area of China
Published in Maryce M. Jacobs, Vitamins and Minerals in the Prevention and Treatment of Cancer, 2018
Nubia Muñoz, Massimo Crespi, Jurgen Wahrendorf, Lu Jian Bang
Compliance with the treatment, assessed by inspection of follow-up records kept by the “barefoot doctors” and by changes in the blood levels 2 and 13.5 months after initiation of the treatment, was excellent. The final examination of the 567 subjects (93 percent) also included oesophagoscopy with at least two biopsies taken. Histologic slides were read independently and blindly by three pathologists. After a final diagnosis was reached by consensus, the code for treatment assignment was opened. The prevalence of micronuclei was also evaluated. For these studies, smears were prepared from exfoliated cells obtained from the buccal mucosa and oesophagus in subsamples of 200 and 170 subjects respectively. The smears were evaluated for the presence of micronuclei by means of 41-6-diamidino-2-phenylindole fluorescent staining.
Telomerase reverse transcriptase (TERT) promotes neurogenesis after hypoxic-ischemic brain damage in neonatal rats
Published in Neurological Research, 2022
Jiao Li, Hai-Ting Liu, Jing Zhao, Hong-Ju Chen
Neonatal rats were anesthetized with 10% chloral hydrate, fixed, perfused with 30 mL of saline, and slowly perfused with 10 mL of 4% paraformaldehyde (PFA). Their brains were then removed and fixed with 4% PFA for 48 h, and frozen sections of 50 µm thickness produced. Sections with consistent positions in each group were used for immunofluorescence staining. Brain sections were incubated with primary antibodies including TERT (sc-377,511, Santa Cruz, CA, USA), Nestin (Abcam), doublecortin (DCX; Abcam), NeuN (Abcam), glial fibrillary acidic protein (GFAP; Abcam), oligodendrocyte marker 4 (O4; R&D, Minneapolis, MN, USA), and myelin basic protein (MBP; Abcam). After incubation with secondary antibodies conjugated with fluorescein, sections were stained with 4′,6-diamidino-2-phenylindole (DAPI). Fluorescent images were obtained using a fluorescence microscope (Nikon 80i, Japan).
Carbon nanotubes promote alveolar macrophages toward M2 polarization mediated epithelial-mesenchymal transition and fibroblast-to-myofibroblast transdifferentiation
Published in Nanotoxicology, 2021
Xiang Zhang, Min Luo, Jiaxiang Zhang, Zhuomeng Yao, Jiaojiao Zhu, Shuxin Yang, Qixing Zhu, Tong Shen
Dulbecco’s modified eagle medium (DMEM) and fetal bovine serum (FBS) were purchased from Hyclone (Logan, UT), interferon-gamma (IFN-γ), and interleukin (IL)-4 were from Peprotech (Rocky Hill, NJ), lipopolysaccharide (LPS), 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide (MTT) and 4′,6-diamidino-2-phenylindole (DAPI) were from Sigma-Aldrich (St. Louis, MO), phycoerythrin-conjugated anti-F4/80 (PE-F4/80, 123110), fluorescein isothiocyanate-conjugated anti-CD11c (FITC-CD11c, 117306), and FITC-conjugated anti-CD206 (FITC-CD206, 141703) were purchased from Biolegend (San Diego, CA). Rat monoclonal anti-F4/80 (ab60343), rabbit polyclonal anti-CD206 (ab64693), rabbit polyclonal anti-IRF4 antibody (ab104803), rabbit monoclonal anti-IRF5 antibody (ab181553), mouse monoclonal anti-E-cad (ab76055), rabbit monoclonal anti-Vim (ab92547), rabbit monoclonal anti-α-SMA (ab32575), rabbit polyclonal anti-COL I (ab34710), mouse monoclonal anti-β-actin (ab20272) and TGF-β inhibitor LY364947 (ab141890) were purchased from Abcam (Cambridge, MA). Rabbit monoclonal anti-CD11c (97585) was from Cell Signaling Technology (Beverley, MA). ELISA Kit was from Calvin Biotechnology Co., Ltd (Suzhou, China), Pierce Chromogenic Endotoxin Quant Kit (A39552S) was from Thermo Fisher Scientific (Waltham, MA), IgG was from Zhongshan Jinqiao Biotechnology Co., Ltd (Beijing, China).
Pulmonary toxicity of synthetic amorphous silica – effects of porosity and copper oxide doping
Published in Nanotoxicology, 2021
Niels Hadrup, Kukka Aimonen, Marit Ilves, Hanna Lindberg, Rambabu Atluri, Nicklas M. Sahlgren, Nicklas R. Jacobsen, Kenneth K. Barfod, Trine Berthing, Alan Lawlor, Hannu Norppa, Henrik Wolff, Keld A. Jensen, Karin S. Hougaard, Harri Alenius, Julia Catalan, Ulla Vogel
The level of DNA strand breaks was assessed in BAL cells, and lung and liver tissue in the intratracheal instillation study as tail percent DNA, measured by the comet assay using the IMSTAR system as previously described (Jackson et al. 2013). Negative and positive controls included on all slides were A549 cells exposed to 0 or 30 µM of H2O2, respectively. The frequency of micronuclei was scored in 2000 normochromatic erythrocytes from peripheral blood per mouse, as previously described (Lindberg et al. 2012), 28 d post-instillation. At the same time-point, the lungs of animals treated with the highest dose of each material were assessed for DNA double-strand breaks by the γ-H2AX assay (Plappert-Helbig et al. 2019). Immunofluorescent γ-H2AX staining was performed on formalin-fixed paraffin-embedded lung samples after deparaffination and antigen retrieval by boiling. An autostainer was used for primary (rabbit monoclonal anti-gamma H2AX phospho-Ser139) and secondary (goat anti-rabbit IgG) antibody incubations and for tyramide amplification of the fluorescent signal (Alexa Fluor™ 488 Tyramide SuperBoost™ Kit; ThermoFisher Scientific) according to manufacturer’s instructions. Samples were counterstained with 4′,6-diamidino-2-phenylindole and digitized with 20x fluorescent scanning. Expression of γ-H2AX foci was analyzed by a digital microscope application. For each sample, all nuclei in four randomly selected annotations (200 × 200 µm) were classified as negative, weak positive (≤3 foci), positive (>3 foci), or apoptotic (pan-stained nucleus).