VEGF, VEGFR2 and GSTM1 polymorphisms in outcome of multiple myeloma patients treated with thalidomide-based regimens

Lopes‐Aguiar, Leisa; Delamain, Márcia Torresan; Brito, Angelo Borsarelli Carvalho; Lourenço, Gustavo Jacob; Costa, Ericka Francislaine Dias; Oliveira, Gislaine B.; Vassallo, José; Souza, Cármino Antônio de; Lima, Carmen Sílvia Passos

doi:10.1038/bcj.2017.58

Cited by 6 publications

(6 citation statements)

References 15 publications

(30 reference statements)

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“…In our research, we observed the association of the GSTM1 present genotype with shorter OS (at the level of tendency) and PFS of MM patients. Multivariate Cox analysis showed that patients with GSTM1 present genotype had lower chances for longer PFS, which is consistent with the research of Lopes-Aguiar et al (19). They noted shorter OS and event-free survival (EFS) in patients with GSTM1 present genotype who did not receive ASCT after chemotherapy (19).…”

Section: Discussionsupporting

confidence: 91%

“…Multivariate Cox analysis showed that patients with GSTM1 present genotype had lower chances for longer PFS, which is consistent with the research of Lopes-Aguiar et al (19). They noted shorter OS and event-free survival (EFS) in patients with GSTM1 present genotype who did not receive ASCT after chemotherapy (19). It is possible that the presence of the GSTM1 gene and activity of the respective GST enzyme affects the treatment of MM patients.…”

Section: Discussionsupporting

confidence: 91%

“…Both MM and CLL are derived from B cells, which points to the role of GSTT1 and GSTM1 polymorphisms in the pathogenesis of B-cell malignancies. Few studies are focused on GSTT1 and GSTM1 polymorphisms in MM (18, 19). In our research, we observed the association of the GSTM1 present genotype with shorter OS (at the level of tendency) and PFS of MM patients.…”

Section: Discussionmentioning

confidence: 99%

“…In the current study, we investigated the influence of polymorphisms in GSTT1, GSTM1 , and TNF- α genes as genetic indicators of risk and progression of MM. A few similar studies have assessed the significance of GSTT1 and GSTM1 polymorphisms in MM (18, 19). However, these reports did not examine the relationship between the efficacy of bortezomib treatment ( in vivo and in vitro ) and combination with −308 G>A and −238G>A TNF -α polymorphisms.…”

Section: Introductionmentioning

confidence: 99%

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The Association of GSTT1, GSTM1, and TNF-α Polymorphisms With the Risk and Outcome in Multiple Myeloma

et al. 2019

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Oxidative stress and systemic inflammation are closely linked with increased risk of cancer development. Tumor necrosis factor alpha (TNF-α) is one of the pro-inflammatory cytokines. Glutathione S-transferases (GSTs) are enzymes involved in oxidative stress handling. Polymorphisms of genes encoding mentioned molecules may potentially influence the risk and the outcome in neoplastic diseases. Multiple myeloma (MM) is a hematological malignancy characterized by clonal, atypical plasma cell proliferation. In the present study we investigated the association of deletion polymorphisms in GSTT1/GSTM1 genes and single nucleotide polymorphisms (SNPs) in the TNF-α gene at positions −308/−238 with the risk and outcome in MM and sensitivity to bortezomib under in vitro conditions. One hundred newly diagnosed MM patients and 100 healthy blood donors were genotyped by means of multiplex PCR (for GSTs) and PCR-RFLP (for TNF-α). In a subgroup of 50 MM patients, bone marrow cells were treated with bortezomib in vitro. Patients with −238GA+AA or GSTT1-null genotypes had 2.0 (p = 0.002) or 2.29 (p = 0.013) fold increased risk of MM. The interaction effects and risk of MM were observed in GSTT1/GSTM1-null (OR = 2.82, p = 0.018), −308/−238GA+AA (OR = 5.63, p < 0.001), as well as in all combinations of −308 with GSTs. The −308/−238GA+AA genotypes in comparison to GG were associated with earlier MM onset−61.14 vs. 66.86 years (p = 0.009) and 61.72 vs. 66.52 years (p = 0.035), respectively. Patients with GSTM1-present had shorter progression-free-survival (15.17 vs. 26.81 months, p = 0.003) and overall-survival (22.79 vs. 34.81 months, p = 0.039) compared with GSTM1-null. We did not observe relationship between response rate and studied polymorphisms. The in vitro study revealed significantly higher number of apoptotic cells at 12 nM of bortezomib in GSTT1-present, GSTM1-null/present, −308GG and −238GG/GA+AA genotypes. Our findings comprise large analysis of studied polymorphisms in MM.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Association of GSTT1, GSTM1, and TNF-α Polymorphisms With the Risk and Outcome in Multiple Myeloma

et al. 2019

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“…In parallel, DE analysis performed on iVECs highlighted the upregulation of GSTM1 and PALD1 in cells derived from old vs. young donors. GSTM1 is generally activated in presence of oxidative stress and inflammatory conditions ( Lopes-Aguiar et al, 2017 ), while PALD1 is an endothelial-specific gene inhibiting endothelial junction stability ( Nitzsche, 2016 ). To test if these genes were actually dysregulated in human donors, we analyzed human skin biopsies and found that CD31+ VECs from old vs. young healthy donors indeed expressed higher levels of PALD1 (194.9 ± 30.0% vs. 100.0±24.3% after normalization, Figure 2D and F ; Videos 4 and 5 ) and GSTM1 ( Figure 2—figure supplement 3 ).…”

Section: Resultsmentioning

confidence: 99%

Direct reprogramming of human smooth muscle and vascular endothelial cells reveals defects associated with aging and Hutchinson-Gilford progeria syndrome

Bersini

Schulte

Huang

et al. 2020

eLife

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Vascular dysfunctions are a common feature of multiple age-related diseases. However, modeling healthy and pathological aging of the human vasculature represents an unresolved experimental challenge. Here, we generated induced vascular endothelial cells (iVECs) and smooth muscle cells (iSMCs) by direct reprogramming of healthy human fibroblasts from donors of different ages and Hutchinson-Gilford Progeria Syndrome (HGPS) patients. iVECs induced from old donors revealed upregulation of GSTM1 and PALD1, genes linked to oxidative stress, inflammation and endothelial junction stability, as vascular aging markers. A functional assay performed on PALD1 KD VECs demonstrated a recovery in vascular permeability. We found that iSMCs from HGPS donors overexpressed bone morphogenetic protein (BMP)−4, which plays a key role in both vascular calcification and endothelial barrier damage observed in HGPS. Strikingly, BMP4 concentrations are higher in serum from HGPS vs. age-matched mice. Furthermore, targeting BMP4 with blocking antibody recovered the functionality of the vascular barrier in vitro, hence representing a potential future therapeutic strategy to limit cardiovascular dysfunction in HGPS. These results show that iVECs and iSMCs retain disease-related signatures, allowing modeling of vascular aging and HGPS in vitro.

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Integration of transcriptomics and metabolomics reveals anlotinib-induced cytotoxicity in colon cancer cells

Jia

Zhang

Tian

et al. 2021

Gene

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VEGF, VEGFR2 and GSTM1 polymorphisms in outcome of multiple myeloma patients treated with thalidomide-based regimens

Cited by 6 publications

References 15 publications

The Association of GSTT1, GSTM1, and TNF-α Polymorphisms With the Risk and Outcome in Multiple Myeloma

The Association of GSTT1, GSTM1, and TNF-α Polymorphisms With the Risk and Outcome in Multiple Myeloma

Direct reprogramming of human smooth muscle and vascular endothelial cells reveals defects associated with aging and Hutchinson-Gilford progeria syndrome

Integration of transcriptomics and metabolomics reveals anlotinib-induced cytotoxicity in colon cancer cells

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