Predictive Role of Midtreatment Changes in Survivin, GSTP1, and Topoisomerase 2α Expressions for Pathologic Complete Response to Neoadjuvant Chemotherapy in Patients With Locally Advanced Breast Cancer

Eralp, Yeşim; Keskın, Serkan; Akişık, Ebru E.; İğci, Abdullah; Müslümanoğlu, Mahmut; Yılmaz, Seher; Tunacı, Mehtap; Çamlıca, Hakan; Tuzlali, Sıtkı; Saip, Pınar; Dalay, Nejat; Ozmen,; Topuz, Erkan

doi:10.1097/coc.0b013e318243913f

Cited by 11 publications

(8 citation statements)

References 49 publications

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“…As immortalization is also a first step of carcinogenesis and a variety of human cancer cells including breast, colon, kidney, lung, and ovarian cancer cells share not only genomic instability, loss of senescence genes, mutation in p53 genes, and high proliferation rate but also the constitutively high expression of GSTP1 [ 25 – 27 ], the role of GSTP1 in HaCaT cells might be distinct from that of the normal cells. This is also supported by the fact that, in addition to its enzyme activity in the conjugation of reduced glutathione to a wide variety of electrophilic substrates, GSTP1 was also found to inhibit the two important nonsubstrate ligands by direct protein-protein interactions, c-Jun N-terminal kinase (JNK) and TNF receptor-associated factor 2 (TRAF2), a member of the TNF receptor-associated factor protein of JNK and p38-MAPK signalling complexes [ 28 – 30 ]. As these two MAP kinases are associated with signalling pathways of stress response and apoptosis [ 30 – 32 ], their inhibition by the high level of GSTP1 might be beneficial in inhibition of apoptosis and maintenance of high proliferation rate in HaCaT cells.…”

Section: Discussionmentioning

confidence: 99%

Effects of Ginger Phenylpropanoids and Quercetin on Nrf2-ARE Pathway in Human BJ Fibroblasts and HaCaT Keratinocytes

Schadich

Hlaváč

Volná

et al. 2016

BioMed Research International

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Quercetin and phenylpropanoids are well known chemoprotective compounds identified in many plants. This study was aimed at determining their effects on activation of Nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant response element (Nrf2-ARE) signalling pathway and expression of its important downstream effector phase II detoxification enzyme glutathione-S-transferase P1 (GSTP1) in BJ foreskin fibroblasts and skin HaCaT keratinocytes. Cell lines and their corresponding Nrf2-ARE luciferase reporter cells were treated by ginger phenylpropanoids and quercetin for 10 h and the level of Nrf2 activity was subsequently determined. Both, ginger phenylpropanoids and quercetin, significantly increased the level of Nrf2 activity. Subsequent western blot analyses of proteins showed the increased expression level of glutathione-S-transferase P1 (GSTP1) in BJ cells but not in HaCaT cells. Such phenomenon of unresponsive downstream target expression in HaCaT cells was consistent with previous studies showing a constitutive expression of their GSTP1. Thus, while both ginger phenylpropanoids and quercetin have the property of increasing the level of Nrf2 both in HaCaT and in BJ cells, their effects on its downstream signalling were mediated only in BJ cells.

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Section: Discussionmentioning

confidence: 99%

Effects of Ginger Phenylpropanoids and Quercetin on Nrf2-ARE Pathway in Human BJ Fibroblasts and HaCaT Keratinocytes

Schadich

Hlaváč

Volná

et al. 2016

BioMed Research International

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“…Finally, the finding that GSTP1-positive prostate cancer subset is substantially over-represented among prostate cancers from Black compared White men could be of importance from the standpoint of treatment of lethal prostate cancer, providing a potential biological underpinning, at least in part, for the observed disparate outcomes for Black men. In breast cancer, the presence or absence of GSTP1 expression predicts response to cytotoxic chemotherapy, particularly to the taxanes docetaxel and paclitaxel (58)(59)(60)(61) . Forced expression of the enzyme in GSTP1-negative breast cancer cells confers docetaxel resistance (58) .…”

Section: Discussionmentioning

confidence: 99%

GSTP1 positive prostatic adenocarcinomas are more common in Black than White men in the United States

Vidal

Zheng

Hicks

et al. 2020

Preprint

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GSTP1 is a member of the Glutathione-S-transferase (GSTS) family silenced by CpG island DNA hypermethylation in 90-95% of prostate cancers. However, prostate cancers expressing GSTP1 have not been well characterized. We used immunohistochemistry against GSTP1 to examine 1673 primary prostatic adenocarcinomas on TMAs with redundant sampling from the index tumor from prostatectomies. GSTP1 protein was positive in at least one TMA core in 7.7% of cases and in all TMA cores in 4.4% of cases. The percentage of adenocarcinomas from Black patients who had any GSTP1 positive TMA cores was 14.9%, which was 2.5 times higher than the percentage from White patients (5.9%; P < 0.001). Further, the percentages of tumors from Black patients who had all TMA spots positive for GSTP1 (9.5%) was 3-fold higher than the percentage from White patients (3.2%; P<0.001). The increased percentage of GSTP1 positive cases in Black men was present only in ERG positive cases. By in situ hybridization, GSTP1 mRNA expression was concordant with protein staining, supporting the lack of silencing of at least some GSTP1 alleles in GSTP1-positive tumor cells. This is the first report revealing that the GSTP1-positive prostate cancer subset is substantially over-represented among prostate cancers from Black compared to White men. This observation should prompt additional studies to determine whether GSTP1 positive cases represent a distinct molecular subtype of prostate cancer and whether GSTP1 expression could provide a biological underpinning for the observed disparate outcomes for Black men.

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“…The cell line is particularly attractive for development of new treatment strategies for breast cancers that are unresponsive to conventional chemotherapy. For example, IOWA-1T cells have relative overexpression of GSTP1, which was reported to be responsible for doxorubicin resistance 26,27 and may contribute to doxorubicin resistance of IOWA-1T cells.…”

Section: Discussionmentioning

confidence: 99%

A Novel Animal Model for Locally Advanced Breast Cancer

et al. 2014

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Background Locally advanced breast cancer (LABC) poses complex management issues due to failure of response to chemotherapy and progression to local complications such as skin erosion, superinfection and lymphedema. Most cell line and animal models are not adequate to study LABC. Methods A patient-derived xenograft (IOWA-1T) from a patient with LABC was characterized for expression profile, short tandem repeat (STR) profile, oncogenic mutations, xenograft growth and response to therapy. Results STR profile authenticated the cell line as derived from a human female. The primary tumor and derived xenografts were weakly ERα-positive (<5%), PgR-negative and HER2 non-amplified. Expression array profile compared to MCF-7 and BT-549 cell lines indicate that IOWA-1T was more closely related to basal breast cancer. IOWA-1T harbors a homozygous R248Q mutation of the TP53 gene and in vitro invasion assay was comparable to BT-549, and greater than MCF-7. IOWA-1T xenografts developed palpable tumors in 9.6±1.6 days, compared to 49±13 days for parallel experiments with BT-20 cells (p<0.002). Tumor xenografts became locally advanced, growing to >2 cm in 21.6±2 days characterized by skin erosion necessitating euthanasia. The SUMO inhibitor anacardic acid inhibited the outgrowth of IOWA-1T xenografts, while doxorubicin had no effect on tumorigenesis. Conclusions IOWA-1T is a novel cell line with an expression pattern consistent with basal breast cancer. Xenografts recapitulated LABC and provide a novel model for testing therapeutic drugs that may be effective in cases resistant to conventional chemotherapy.

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Predictive Role of Midtreatment Changes in Survivin, GSTP1, and Topoisomerase 2α Expressions for Pathologic Complete Response to Neoadjuvant Chemotherapy in Patients With Locally Advanced Breast Cancer

Abstract: Downregulation of GSTP1 is a significant predictor of pCR and improved progression-free survival during anthracycline-based and taxane-based neoadjuvant chemotherapy in patients with locally advanced breast cancer.

Cited by 11 publications

References 49 publications

Effects of Ginger Phenylpropanoids and Quercetin on Nrf2-ARE Pathway in Human BJ Fibroblasts and HaCaT Keratinocytes

Effects of Ginger Phenylpropanoids and Quercetin on Nrf2-ARE Pathway in Human BJ Fibroblasts and HaCaT Keratinocytes

GSTP1 positive prostatic adenocarcinomas are more common in Black than White men in the United States

A Novel Animal Model for Locally Advanced Breast Cancer

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