Combined radiotherapy and chemotherapy
Michael C. Joiner, Albert J. van der Kogel in Basic Clinical Radiobiology, 2018
As a consequence of this cell-cycle phase selective cytotoxicity of chemotherapeutic agents, the remaining surviving cells could in principle be synchronized. If radiation could be delivered when these ‘synchronized’ cells have reached a more radiosensitive phase of the cell cycle (e.g. G2–mitosis), a tremendous potentiation of the radiation effect could be observed. Such a mechanism of interaction between drugs and ionizing radiation has often been reported in pre-clinical experimental models (e.g. [23]). However, in the clinic, due to much greater intra-tumour heterogeneity and also the difficulty in assessing the appropriate timing between drug administration and radiotherapy delivery, it is unlikely that cell synchronization can be successfully exploited. Furthermore, considering that radiotherapy is typically delivered on a fractionated basis, it is also likely that this effect would be lost after a few fractions.
Cell Biology
C.S. Sureka, C. Armpilia in Radiation Biology for Medical Physicists, 2017
Cell synchronization is a process by which cells at different stages of the cell cycle are brought to the same phase. Thus, a synchronized culture is one in which cells of similar age progress as a group through the division.
Role of Nonhistone Chromosomal Proteins in Selective Gene Expression
Gerald M. Kolodny in Eukaryotic Gene Regulation, 2018
While taken together these results seem to support control of histone gene readout residing at least in part at the transcriptional level, caution must be exercised in interpreting the in vitro translation and transcription experiments. The limits of detection of histones synthesized in vitro when very small quantities of RNA template are available leave something to be desired. Interpretation of data from in vitro nuclear transcription experiments is complicated by an inability to establish definitively the initiation of RNA chains in vitro and by the presence of endogenous nuclear histone mRNA sequences. Results from in vitro chromatin transcription experiments can be misleading since trancription is carried out with bacterial RNA polymerase, and endogenous chromatin-associated RNA sequences can also interfere with evaluation of nucleic acid hybridization. It must also be pointed out that because, in the experiments just described, hybridization was carried out in RNA excess using unlabeled RNA and a 3H-labeled histone DNA complementary to the mRNAs for the five histones, the presence of rapidly turning over histone mRNA sequences in the nuclear RNA or in the nuclear or chromatin transcripts of G, cells might not have been detected. In fact, Melli et al.521 have detected the presence of histone mRNA sequences in the nucleus throughout the cell cycle of HeLa cells by hybridizing 3H-labeled RNA with excess sea urchin histone DNA. However, there are some reservations concerning the experiments of Melli et al.521 (1) The method utilized for cell synchronization was double thymidine block, a procedure which results in at least 20% of the G1 and G2 cells actually being S phase cells (as measured by 3H-thymidine labeling and autoradiography). This is in contrast to experiments in which the HeLa cDNA probe was used and in which G1, cells were obtained by mitotic selective detachment, a procedure which yields a population of Gi cells containing less than 0.1 % S phase cells. (2) Hybridization analysis of HeLa cell RNAs was carried out with sea urchin DNA and there appears to be only 10 to 15% sequence homology between human and sea urchin histone sequences.556
Pharmaceutical strategies in improving anti-tumour efficacy and safety of intraperitoneal therapy for peritoneal metastasis
Published in Expert Opinion on Drug Delivery, 2021
Puxiu Wang, Xiujuan Qu, Xiaofang Che, Qiuhua Luo, Xing Tang, Yunpeng Liu
Some microtubule-arresting drugs (such as paclitaxel) have been proven to improve gene transfection efficiency, and can be co-applied with therapeutic genes in tumor therapy [96]. The underlying mechanism may be such that low dosage paclitaxel promoted endosome/lysosome escape and nuclear entry of the genes by inducing cell synchronization at the G2-M phase. Low-dosage paclitaxel encapsulated nanoparticles (P-DPP), delivered the co-encapsulated paclitaxel and VSVMP to the same tumor cells and provided a good platform for their synergistic action [97]. Combination of paclitaxel loaded TPM also could increase the efficacy of siRNA therapy [98]. Positively charged PEGylated cationic liposome (PCat) formed multi-lamellar structures with negatively charged siRNA and improved their stability and cellular uptake [99]. In addition, the combination of TPM and PCat-siSurvivin could improve the transfection of siRNA and anti-tumor efficacy by synergistic effect: a combinatorial therapy involving cisplatin and siRNA-mediated DJ-1 protein suppression was tested for metastatic ovarian cancer [100]. PEG-coated poly (propyleneimine) (PPI) nanoparticles were further conjugated with Luteinizing hormone-releasing hormone (LHRH) peptide to be used as tumor cell targeting vectors of siRNA. In conclusion, the combination of IP gene therapy and chemotherapeutic agents seems to be a potent strategy with which to improve the anti-tumor efficacy through different cellular pathways.
Identification of novel cis-mutations in the GJA8 gene in a 3-generation Iranian family with autosomal dominant congenital nuclear cataract
Published in Ophthalmic Genetics, 2022
Neda Jabbarpour, Hassan Saei, Mohammad Hossein Jabbarpoor Bonyadi, Mortaza Bonyadi
Congenital cataracts are clinically and genetically diverse. There are more than 300 genes identified to be involved in the development of congenital cataract, including syndromic and non-syndromic cataracts (1). Non-syndromic cataracts are inherited in 8.3 to 25% of cases, of which 76–89% are inherited as autosomal dominant, 7% as autosomal recessive, and 2–10% as X-linked. Congenital cataract, which could lead to blindness or amblyopia in infants, is estimated to have an incidence of 1 to 6 in 10,000 live birth (2). The C × 50 and C × 46‘s N-terminal domains are hotspots for genetic variants related to congenital cataracts (1). Gap junction proteins, encoded by connexin family of genes (abbreviated CX), are frequently identified by their molecular weights, for example, C × 50 (GJA8) is the 50 kDa connexin protein. An alternative nomenclature is the gap junction protein system, which classifies connexins according to their α (GJA) and β (GJB) forms (3). These proteins provide a pathway for the intercellular exchanges of ions, small metabolites, and second messengers which are essential for cell synchronization, growth and development (4). Three connexin isoforms known as C × 43, C × 46, and C × 50 are reported to be expressed in mammalian lens (5). Gap Junction protein alpha-8 (GJA8) gene encodes a transmembrane connexin protein (CX50) essential for the maturation of lens fiber cells and their growth. This protein is a connexin of the ocular lens, which maintains ionic and water balance and transparency and optical properties of the lens (6). Several previous studies have shown the association of this gene with zonular pulverulent cataracts, nuclear progressive cataracts, and cataract-microcornea syndrome with autosomal dominant pattern in the pedigree (7–10).
An Olive Leaf Extract Rich in Polyphenols Promotes Apoptosis in Cervical Cancer Cells by Upregulating p21Cip/WAF1 Gene Expression
Published in Nutrition and Cancer, 2019
Donatella Vizza, Simona Lupinacci, Giuseppina Toteda, Francesco Puoci, Parisi Ortensia I, Anna De Bartolo, Danilo Lofaro, Luca Scrivano, Renzo Bonofiglio, Antonella La Russa, Martina Bonofiglio, Anna Perri
Human cervix cancer cells, HeLa (ATCC), were grown in Minimum Essential Medium (Sigma Aldrich, Milano, Italy) containing 10% Fetal Bovine Serum (FBS, Sigma Aldrich), 1% Glutammine (Sigma Aldrich), 1% non-essential amminoacids (Sigma Aldrich) and 1 mg ml−1 penicillin/streptomycin (P/S), (Sigma Aldrich). All experiments were performed, after 24 h of cell synchronization, in serum free medium. The control was treated with the vehicle [ethanol/water 40/60 (v/v) (untreated, −)].
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