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My Aashis
My Aashis is a highly anticipated online store. We offer a broad range of high-quality and ethically sourced products, including jewelry, home decorations, and contemporary furniture. We are committed to providing our customers with the best shopping experience, and we promise that you will be able to find everything you desire in our store. Please don't hesitate to write us if you get any questions or comments about myaashis. Visit - https://www.myaashis.com
July 25, 2023
JC
Crush cancer with CRISPR
Primary glioblastoma (GBM) is a highly aggressive central nervous system (CNS) cancer that is challenging to treat, with a median survival of 12–15 months despite multimodal treatment regimens. GBM is highly diffuse and infiltrates the normal brain parenchyma, which makes it impossible to surgically remove the tumor, and residual tumors will inevitably recur. In addition, GBM has significant tumor heterogeneity, with subpopulations of cells displaying different mutations, copy number aberrations, gene expression patterns, and epigenetic status. This heterogeneity renders treatment targeting specific molecular processes (https://www.creative-biolabs.com/targeted-delivery/module-delivery-systems.htm) ineffective, as it can generate tumor recurrence from clones with different genetic compositions.
Temozolomide (TMZ) is currently the first-line chemotherapeutic agent for GBM, and the methylation status of the O-6-methylguanine-DNA methyltransferase (MGMT) promoter determines the sensitivity to TMZ treatment. Although TMZ-based therapies have shown relatively few side effects and prolonged survival in patients with GBM, the majority of patients will still manage disease progression. At the time of tumor recurrence, 23% of MGMT-silenced GBM patients exhibited hypermutated tumors associated with poor survival. For patients with recurrent astrocytomas and oligodendrogliomas, this percentage is even higher. TMZ increases the incidence of somatic mutations, which, coupled with the instability of the tumor genome and loss of the DNA mismatch repair (MMR) pathway, leads to hypermutation. And critically, there are no effective treatments for hypermutated gliomas. Therefore, there is an urgent need to develop new therapeutic strategies to effectively eliminate GBM cells, regardless of their mutational and epigenetic characteristics.
Recently, a collaboration of researchers from the Gladstone Institutes, the University of California, Berkeley, and other institutions published a paper in Cell Reports entitled: Targeting the non-coding genome and temozolomide signature enables CRISPR-mediated glioma oncolysis. The study develops a CRISPR-based cancer-crushing method that targets the non-coding repeats specific to cancer cells to remove them for the treatment of glioblastoma.
The CRISPR system, derived from the adaptive immune systems of bacteria and archaea, is capable of introducing RNA-guided DNA double-strand breaks (DSBs) at targeted sites in the genome, allowing programmable gene editing in human cells. And a potential risk of CRISPR therapies is precisely because of the cytotoxic effects that may result from the DNA double-strand breaks they produce.
Previously, George Church, Luhan Yang, and others used CRISPR-Cas9 gene editing to achieve 62 and 25 gene edits in porcine cell lines and primary cells in vivo in living pigs, respectively, in order to construct gene-edited pigs that could be used for human organ transplantation. But we don't yet know how many such DNA double-strand breaks can eliminate a cell and whether this could be utilized as an effective way to fight cancer.
In this latest study, targeting CNS cancers, the team proposes to harness the cytotoxic effects of DNA double-strand breaks generated during CRISPR-Cas9 gene editing by targeting unique repetitive sequences in the tumor genome as a new strategy for treating recurrent hypermutated gliomas.
Specifically, the team identified germ cell defects in the DNA damage response (DDR) gene that may contribute to the high mutational load of primary GBM tumors, as well as somatic mutations in the TERT promoter, which is critical for the immortalization of GBM cells. Furthermore, recurrent GBM is genetically distinct from primary GBM, with the former having additional mutations associated with malignant progression and hypermutation.
The study also found that recurrent GBM hypermutations induced by treatment with TMZ, a first-line chemotherapeutic agent for GBM, can result in unique, cancer-specific, non-coding repeat sequences. Importantly, these non-coding repeats can be targeted by CRISPR-Cas9, which cleaves the cancer cell genome at these sites, fragmenting the genome and leading to DNA damage and cell death, thereby selectively removing patient-derived recurrent GBM cell lines while preserving normal cells.
This CRISPR-based cancer smashing approach presents an innovative therapeutic paradigm that is independent of the genetic and epigenetic origins of tumors, translating tumor mutational load and TMZ signaling from chemotherapeutic agents in hypermutated cancers into a potential therapeutic pathway.
Jan 25
Movers by the Sea
Our expert teams specialize in moving and packing throughout San Diego and Orange Counties, known for speedy, professional, and skilled services. Our 26-ft trucks come fully equipped with our own tools, floor & door protection, dollies, moving blankets, and tie-downs. We offer comprehensive solutions for loading, unloading, packing, and unpacking, catering to office, apartment, or house relocations, insurance pack outs/backs, or moves within the same complex or storage facility.
Jan 25
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