scholarly journals Impact of Expression Levels of Platinum-uptake Transporters Copper Transporter 1 and Organic Cation Transporter 2 on Resistance to Anthracycline/Taxane-based Chemotherapy in Triple-negative Breast Cancer

2015 ◽  
Vol 9 ◽  
pp. BCBCR.S27534
Author(s):  
Risa Takeda ◽  
Ayano Naka ◽  
Naoki Ogane ◽  
Yoichi Kameda ◽  
Kae Kawachi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Organic Cation ◽  
Organic Cation Transporter ◽  
Platinum Drugs ◽  
Ki 67 ◽  
Copper Transporter ◽  
Organic Cation Transporter 2 ◽  
Uptake Transporters ◽  
Copper Transporter 1

Adding platinum drugs to anthracycline/taxane (ANC-Tax)-based neoadjuvant chemotherapy (NAC) improves pathological complete response (pCR) rates in triple-negative breast cancer (TNBC). Copper transporter 1 (CTR1) and organic cation transporter 2 (OCT2) critically affect the uptake and cytotoxicity of platinum drugs. We immunohistochemically determined CTR1 and OCT2 levels in pre-chemotherapy biopsies from 105 patients with HER2-negative breast cancer treated with ANC-Tax-based NAC. In the TNBC group, Ki-67high [pathological good response (pGR), P = 0.04] was associated with response, whereas CTR1high (non-pGR, P = 0.03), OCT2high (non-pGR, P = 0.01; non-pCR, P = 0.03), and combined CTR1high and/or OCT2high (non-pGR, P = 0.005; non-pCR, P = 0.003) were associated with non-response. In multivariate analysis, Ki-67high was an independent factor for pGR and CTR1 for non-pGR. Combined CTR1/OCT2 was a strong independent factor for non-pGR. However, no variables were associated with response in luminal BC. These results indicate that platinum uptake transporters are predominantly expressed in ANC-Tax-resistant TNBCs, which implies that advantage associated with adding platinum drugs may depend on high drug uptake.

scholarly journals EFFECTS OF CURCUMIN AND NANOCURCUMIN ON CISPLATIN-INDUCED NEPHROTOXICITY IN RAT: COPPER TRANSPORTER 1 AND ORGANIC CATION TRANSPORTER 2 AS DRUG TRANSPORTERS

2018 ◽  
Vol 10 (1) ◽  
pp. 172
Author(s):  
Deliana Nur Ihsani Rahmi ◽  
Melva Louisa ◽  
Vivian Soetikno
Keyword(s):  
Single Dose ◽  
Organic Cation ◽  
Rat Kidney ◽  
Kidney Tissue ◽  
Organic Cation Transporter ◽  
Copper Transporter ◽  
Renal Tubular Cells ◽  
Organic Cation Transporter 2 ◽  
Renal Tubular ◽  
Copper Transporter 1

Objective: This study aimed to investigate the efficacy of curcumin (CMN) and nanocurcumin (NC) at preventing cisplatin (CDPP)-inducednephrotoxicity.Methods: Two membrane transporters, copper transporter 1 (CTR1) and organic cation transporter 2 (OCT2), have been identified involved in activeaccumulation of CDPP into renal tubular cells. We analyzed OCT2 transcription levels in rat kidney tissue and determined whether renoprotectivemechanism of CMN involves CTR1. Rats were randomly divided into five groups: (1) Control, (2) CDPP (7 mg/kg as single dose (i.p.), (3) CDPP+CMN(7 mg/kg CDPP as a single dose, i.p.+100 mg/kg/day of CMN), (4) CDPP+50 mg NC (7 mg/kg CDPP as single dose, i.p.+50 mg/kg/day NC), and(5) CDPP+100 mg NC (7 mg/kg CDPP as single dose, i.p.+100 mg/kg/day NC). Quantitative reverse transcription-polymerase chain reaction wasperformed to calculate relative expression of CTR1 and OCT2 genes in rat kidney.Results: Expression of CTR1 was unassociated with administration of CMN or NC, indicating CTR1 is uninvolved in renoprotective mechanism of CMN.The administration of 100 mg/kg/day NC increased expression of OCT2; this increase was higher compared with normal expression levels. This maybe due to another regulatory mechanism from the CMN itself.Conclusion: NC has a better renoprotective effect compared with curcumin, suggested by the increased OCT2 expression on its administration inCDPP-treated rats.

Relevance of copper transporter 1 and organic cation transporters 1–3 for oxaliplatin uptake and drug resistance in colorectal cancer cells

Metallomics ◽  
2018 ◽  
Vol 10 (3) ◽  
pp. 414-425 ◽  
Author(s):  
I. Buß ◽  
A. Hamacher ◽  
N. Sarin ◽  
M. U. Kassack ◽  
G. V. Kalayda
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Organic Cation ◽  
Organic Cation Transporter ◽  
Organic Cation Transporters ◽  
Copper Transporter ◽  
Colorectal Cancer Cells ◽  
Organic Cation Transporter 2 ◽  
Organic Cation Transporter 1 ◽  
Copper Transporter 1

Copper transporter 1 and organic cation transporter 2 mediate oxaliplatin uptake in sensitive and resistant colorectal cancer cells. Organic cation transporter 1 is involved in oxaliplatin uptake only in sensitive cells underscoring its relevance for oxaliplatin resistance.

scholarly journals Distinct Somatic Alteration Features Identified by Gene Panel Sequencing in Korean Triple-Negative Breast Cancer with High Ki67 Expression

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 416
Author(s):  
Woo Young Sun ◽  
Jina Lee ◽  
Bong Kyun Kim ◽  
Jong Ok Kim ◽  
Joonhong Park
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Hormone Receptor ◽  
Mutation Frequency ◽  
Triple Negative ◽  
Genetic Difference ◽  
Her2 Positive ◽  
Ki 67 ◽  
Hormone Receptor Positive ◽  
Somatic Alteration

This study aimed to clarify the genetic difference between Korean triple-negative breast cancer (TNBC) and other breast cancer (BC) subtypes. TNBC was defined as the absence of hormonal receptors and human epidermal growth factor receptor 2 (HER2) amplification. DNA panel of the Ion Torrent Oncomine Comprehensive Assay (OCA) v3 was performed to identify somatic alteration in 48 specimens. In a total of 102 alterations (37 nonsense, 35 missense, 8 frameshift and 22 amplifications), 30 nucleotide alterations (24 nonsense, 1 missense, and 5 frameshift) were newly identified. The eight most commonly altered genes were PIK3CA, TP53, ERBB2, BRCA2, FANCD2, AKT1, BRCA1, and FANCA. TNBC had significantly lower mutation frequency in PIK3CA (TNBC vs. hormone receptor-positive and HER2-negative BC [HRPBC], p = 0.009), but higher mutation frequency in TP53 (TNBC vs. HRPBC, p = 0.036; TNBC vs. hormone receptor-positive and HER2- positive BC [HHPBC], p = 0.004). TNBC showed frequently higher Ki-67 expression than any positive BC (p = 0.004) due to HRPBC (p < 0.001). TNBC with high Ki-67/unmutated PIK3CA/mutated TP53 appears at a younger age (52.2 ± 7.6 years), compared to other subtypes (63.7 ± 11.0 years). TNBC with high Ki-67/unmutated PIK3CA/mutated TP53 may be related to relatively early onset BCThese findings demonstrate the genomic heterogeneity between TNBC and other BC subtypes and could present a new approach for molecular targeted therapy in TNBC patients.

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