A systematic review of inter-individual differences in the DNA repair processes involved in melphalan monoadduct repair in relation to treatment outcomes

Kan, Maia van; Burns, Kathryn; Helsby, Nuala A.

doi:10.1007/s00280-021-04340-z

Cited by 11 publications

(4 citation statements)

References 43 publications

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“…Studies on ERCC1 rs3212961 were controversial, although the rs3212961 C allele was associated with a shorter overall survival in gastric cancer patients [39] and a higher risk for non-Hodgkin lymphoma development [40], which were consistent with results of the present study. However, we found no evidence for the relation between the three SNPs of the PARP4 gene examined in the present study and DNA damage or lung oxidation, although rs17080653, another intronic variant in PARP4, showed a protective effect on head and neck cancer [41] and inter-individual differences in DNA repair processes [42].…”

Section: Discussioncontrasting

confidence: 92%

Modification Effect of PARP4 and ERCC1 Gene Polymorphisms on the Relationship between Particulate Matter Exposure and Fasting Glucose Level

Kim

Lee

Hong

2022

IJERPH

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Particulate matter (PM) has been linked to adverse health outcomes, including insulin resistance (IR). To evaluate the relationships between exposures to PM10, PM2.5–10, and PM2.5; the serum level of fasting glucose, a key IR indicator; and effects of polymorphisms of two repair genes (PARP4 and ERCC1) on these relations, PMs exposure data and blood samples for glucose measurement and genotyping were collected from 527 Korean elders. Daily average levels of PMs during 8 days, from 7 days before examination to the health examination day (from lag day 7 to lag day 0), were used for association analyses, and mean concentrations of PM10, PM2.5–10, and PM2.5 during the study period were 43.4 µg/m3, 19.9 µg/m3, and 23.6 µg/m3, respectively. All three PMs on lag day 4 (mean, 44.5 µg/m3 for PM10, 19.9 µg/m3 for PM2.5–10, and 24.3 µg/m3 for PM2.5) were most strongly associated with an increase in glucose level (percent change by inter-quartile range-change of PM: (β) = 1.4 and p = 0.0023 for PM10; β = 3.0 and p = 0.0010 for PM2.5–10; and β = 2.0 and p = 0.0134 for PM2.5). In particular, elders with PARP4 G-C-G or ERCC1 T-C haplotype were susceptible to PMs exposure in relation to glucose levels (PARP4 G-C-G: β = 2.6 and p = 0.0006 for PM10, β = 3.5 and p = 0.0009 for PM2.5–10, and β = 1.6 and p = 0.0020 for PM2.5; ERCC1 T-C: β = 2.2 and p = 0.0016 for PM10, β = 3.5 and p = 0.0003 for PM2.5–10, and β = 1.2 and p = 0.0158 for PM2.5). Our results indicated that genetic polymorphisms of PARP4 and ERCC1 could modify the relationship between PMs exposure and fasting glucose level in the elderly.

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Section: Discussioncontrasting

confidence: 92%

Modification Effect of PARP4 and ERCC1 Gene Polymorphisms on the Relationship between Particulate Matter Exposure and Fasting Glucose Level

Kim

Lee

Hong

2022

IJERPH

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“…Melphalan acts by alkylating DNA and causing single-strand DNA breaks as well as other DNA lesions, primarily repaired through the base excision repair (BER) pathway. 6 Poly (ADP-ribose) polymerases (PARP) are a family of enzymes that catalyze the transfer of ADP-ribose to target proteins (poly ADP-ribosylation) and are involved in nucleic acid metabolism, modulation of chromatin structure, DNA synthesis, and DNA repair. 7 PARP are a pivotal component of the BER complex, which consists of DNA ligase III, DNA polymerase β, and the XRCC1 proteins, and contributes to BER response to single-strand DNA breaks.…”

Section: Introductionmentioning

confidence: 99%

<i>PARP1</i> and <i>POLD2</i> as prognostic biomarkers for multiple myeloma in autologous stem cell transplant

et al. 2023

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Multiple Myeloma (MM) is an incurable plasma cell malignancy often treated by autologous stem cell transplant (ASCT). Clinical response to ASCT has been associated with DNA repair efficiency. Here we interrogated the role of the base excision DNA repair (BER) pathway in MM response to ASCT. Across 450 clinical samples and six disease stages, expression levels of genes in the BER pathway were found to be highly upregulated during the development of MM. In a separate cohort of 559 patients with MM treated with ASCT, expression of BER pathway members MPG and PARP3 was positively associated with overall survival (OS) while expression of PARP1, POLD1, and POLD2 was negatively associated with OS. In a validation cohort of 356 patients with MM treated with ASCT, PARP1 and POLD2 findings were replicated. In patients with MM who never received ASCT (n=319), PARP1 and POLD2 were not associated with OS, suggesting that the prognostic effect of these genes may be treatmentdependent. In pre-clinical models of MM, synergy was observed in anti-tumor activity when poly (ADP-ribose) polymerase (PARP) inhibitors (olaparib, talazoparib) were used in combination with melphalan. The negative prognosis associated with PARP1 and POLD2 expression along with the apparent melphalan sensitizing effect of PARP inhibition may suggest this pathway as a potential biomarker in patients with MM in the setting of ASCT. Further understanding of the role of the BER pathway in MM is vital to improve therapeutic strategies related to ASCT.

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“…Melphalan (Mel) is a bifunctional alkylating agent widely used at the clinical level in the treatment of multiple types of cancer and other diseases [ 1 , 2 , 3 , 4 ]. The effectiveness of killing cancer cells of this drug is based on the ability to react extensively with DNA, RNA, and proteins to form interstrand DNA crosslinks, inducing multiple kinds of molecular lesions [ 5 , 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

Solid-State Formation of a Potential Melphalan Delivery Nanosystem Based on β-Cyclodextrin and Silver Nanoparticles

Sierpe

Donoso-González

Lang

et al. 2023

IJMS

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Melphalan (Mel) is an antineoplastic widely used in cancer and other diseases. Its low solubility, rapid hydrolysis, and non-specificity limit its therapeutic performance. To overcome these disadvantages, Mel was included in β-cyclodextrin (βCD), which is a macromolecule that increases its aqueous solubility and stability, among other properties. Additionally, the βCD–Mel complex has been used as a substrate to deposit silver nanoparticles (AgNPs) through magnetron sputtering, forming the βCD–Mel–AgNPs crystalline system. Different techniques showed that the complex (stoichiometric ratio 1:1) has a loading capacity of 27%, an association constant of 625 M−1, and a degree of solubilization of 0.034. Added to this, Mel is partially included, exposing the NH2 and COOH groups that stabilize AgNPs in the solid state, with an average size of 15 ± 3 nm. Its dissolution results in a colloidal solution of AgNPs covered by multiple layers of the βCD–Mel complex, with a hydrodynamic diameter of 116 nm, a PDI of 0.4, and a surface charge of 19 mV. The in vitro permeability assays show that the effective permeability of Mel increased using βCD and AgNPs. This novel nanosystem based on βCD and AgNPs is a promising candidate as a Mel nanocarrier for cancer therapy.

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A systematic review of inter-individual differences in the DNA repair processes involved in melphalan monoadduct repair in relation to treatment outcomes

Cited by 11 publications

References 43 publications

Modification Effect of PARP4 and ERCC1 Gene Polymorphisms on the Relationship between Particulate Matter Exposure and Fasting Glucose Level

Modification Effect of PARP4 and ERCC1 Gene Polymorphisms on the Relationship between Particulate Matter Exposure and Fasting Glucose Level

<i>PARP1</i> and <i>POLD2</i> as prognostic biomarkers for multiple myeloma in autologous stem cell transplant

Solid-State Formation of a Potential Melphalan Delivery Nanosystem Based on β-Cyclodextrin and Silver Nanoparticles

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