Drugging DNA repair to target T-ALL cells

Dasgupta, Yashodhara; Golovine, Konstantin; Nieborowska‐Skorska, Margaret; Luo, Li; Matławska-Wasowska, Ksenia; Mullighan, Charles G.; Skórski, Tomasz

doi:10.1080/10428194.2017.1397662

Cited by 48 publications

(23 citation statements)

References 15 publications

(17 reference statements)

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“…These systems can regulate the release of entrapped drug molecules by specific external stimuli such as light, temperature, magnetic fields, or by internal enzymes (Ruiz-Hernández et al., 2011 ). New synthetic pH-dependent colon delivery systems combination with timed-release, ion-sensitive or ROS-response property are being developed (Dasgupta et al., 2018 ; Sacks et al., 2018 ). Enzyme as a kind of unique stimulant has been more and more used as trigger in controlled release system (Xiong et al., 2012 ).…”

Section: Discussionmentioning

confidence: 99%

An efficient enzyme-triggered controlled release system for colon-targeted oral delivery to combat dextran sodium sulfate (DSS)-induced colitis in mice

Jin

et al. 2021

Drug Delivery

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Oral route colon-targeted drug delivery systems (CDDSs) are desirable for the treatment of ulcerative colitis (UC). However, CDDSs are challenging owing to the physiological and anatomical barriers associated with the gastrointestinal tract (GIT). In this study, we developed an effective enzyme-triggered controlled release system using curcumin–cyclodextrin (CD–Cur) inclusion complex as core and low molecular weight chitosan and unsaturated alginate resulting nanoparticles (CANPs) as shell. The formed CD–Cur–CANPs showed a narrow particle-size distribution and a compact structure. In vitro drug release determination indicated that CD–Cur–CANPs showed pH-sensitive and α-amylase-responsive release characteristics. Furthermore, in vivo experiments demonstrated that oral administration of CD–Cur–CANPs had an efficient therapeutic efficacy, strong colonic biodistribution and accumulation, rapid macrophage uptake, promoted colonic epithelial barrier integrity and modulated production of inflammatory cytokines, reshaped the gut microbiota in mice with dextran sodium sulfate (DSS)-induced colitis. Taken together, our synthetic CD–Cur–CANPs are a promising synergistic colon-targeted approach for UC treatment.

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Section: Discussionmentioning

confidence: 99%

An efficient enzyme-triggered controlled release system for colon-targeted oral delivery to combat dextran sodium sulfate (DSS)-induced colitis in mice

Jin

et al. 2021

Drug Delivery

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“…Microarray data sets were obtained from NCBI GEO (GSE13041). Gene expression profiling was performed as described before [29–30]. Microarray was subset for D-NHEJ genes and HR genes.…”

Section: Methodsmentioning

confidence: 99%

Eradication of LIG4-deficient glioblastoma cells by the combination of PARP inhibitor and alkylating agent

et al. 2018

Self Cite

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Cancer cells often accumulate spontaneous and treatment-induced DNA damage i.e. potentially lethal DNA double strand breaks (DSBs). Targeting DSB repair mechanisms with specific inhibitors could potentially sensitize cancer cells to the toxic effect of DSBs. Current treatment for glioblastoma includes tumor resection followed by radiotherapy and/or temozolomide (TMZ) – an alkylating agent inducing DNA damage. We hypothesize that combination of PARP inhibitor (PARPi) with TMZ in glioblastoma cells displaying downregulation of DSB repair genes could trigger synthetic lethality. In our study, we observed that PARP inhibitor (BMN673) was able to specifically sensitize DNA ligase 4 (LIG4)-deprived glioblastoma cells to TMZ while normal astrocytes were not affected. LIG4 downregulation resulting in low effectiveness of DNA-PK–mediated non-homologous end-joining (D-NHEJ), which in combination with BMN673 and TMZ resulted in accumulation of lethal DSBs and specific eradication of glioblastoma cells. Restoration of the LIG4 expression caused loss of sensitivity to BMN673+TMZ. In conclusion, PARP inhibitor combined with DNA damage inducing agents can be utilized in patients with glioblastoma displaying defects in D-NHEJ.

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“…These proteins coordinate checkpoint regulation and block cell cycle progression to allow sufficient time for DNA repair. If the damage is too severe, cells can be either eliminated by cell death or induced to an irreversible exit from cell cycle at the G1 or G2 phase [ 40 ], therefore preventing inappropriate cell cycle progression in the presence of unrepaired damage. Following double strands break (DSB), proteins acting as sensors of DNA damage signal the lesion to ATM and ATR.…”

Section: Therapy-induced Senescencementioning

confidence: 99%

Cancer Response to Therapy-Induced Senescence: A Matter of Dose and Timing

Mongiardi

Pellegrini

Pallini

et al. 2021

Cancers

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Cellular senescence participates to fundamental processes like tissue remodeling in embryo development, wound healing and inhibition of preneoplastic cell growth. Most senescent cells display common hallmarks, among which the most characteristic is a permanent (or long lasting) arrest of cell division. However, upon senescence, different cell types acquire distinct phenotypes, which also depend on the specific inducing stimuli. Senescent cells are metabolically active and secrete a collection of growth factors, cytokines, proteases, and matrix-remodeling proteins collectively defined as senescence-associated secretory phenotype, SASP. Through SASP, senescent cells modify their microenvironment and engage in a dynamic dialog with neighbor cells. Senescence of neoplastic cells, at least temporarily, reduces tumor expansion, but SASP of senescent cancer cells as well as SASP of senescent stromal cells in the tumor microenvironment may promote the growth of more aggressive cancer subclones. Here, we will review recent data on the mechanisms and the consequences of cancer-therapy induced senescence, enlightening the potentiality and the risk of senescence inducing treatments.

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Drugging DNA repair to target T-ALL cells

Cited by 48 publications

References 15 publications

An efficient enzyme-triggered controlled release system for colon-targeted oral delivery to combat dextran sodium sulfate (DSS)-induced colitis in mice

An efficient enzyme-triggered controlled release system for colon-targeted oral delivery to combat dextran sodium sulfate (DSS)-induced colitis in mice

Eradication of LIG4-deficient glioblastoma cells by the combination of PARP inhibitor and alkylating agent

Cancer Response to Therapy-Induced Senescence: A Matter of Dose and Timing

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