Topoisomerase II alpha expression and the Ki-67 labeling index correlate with prognostic factors in estrogen receptor-positive and human epidermal growth factor type-2-negative breast cancer

Tokiniwa, Hideaki; Horiguchi, Jun; Takata, Daisuke; Kikuchi, Mami; Rokutanda, Nana; Nagaoka, Rin; Sato, Ayako; Odawara, Hiroki; Tozuka, Katsunori; Oyama, Tetsunari; Takeyoshi, Izumi

doi:10.1007/s12282-011-0291-4

Cited by 25 publications

(16 citation statements)

References 32 publications

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“…Abnormal levels of expression of MDR1, MRP1, BMI1 and Topo II were found to be important in impairing tumor chemosensitivity, resulting in MDR (20)(21)(22)(23). P-gp is the best-known and principal mediator of MDR.…”

Section: Discussionmentioning

confidence: 99%

“…Topo II, which can bind to chemotherapeutic agents, with binding of these drugs to the α chain of Topo II inhibiting the proliferation and duplication of DNA in tumor cells (17). Upregulating the expression of Topo II by transfection has been reported to enhance the cytotoxicity of chemotherapy drugs (23,29). Thus, the ability of Mda-7/IL-24 to enhance Topo II expression in Raji and Daudi suggests that it may enhance sensitivity to chemotherapy in vivo.…”

Section: Discussionmentioning

confidence: 99%

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Mda-7/IL-24 enhances sensitivity of B cell lymphoma to chemotherapy drugs

Zhao

Sun

et al. 2016

Oncology Reports

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Abstract. ) is a cytokine encoded by a tumor suppressor gene of the IL-10 family, also known as the melanoma differentiation associated gene-7 (Mda-7) and first discovered in human melanoma cells. Mda-7/IL-24 has been shown to inhibit the proliferation of various human tumor cell lines, but its effect on the sensitivity of B cell lymphoma to chemotherapy agents is not yet clear. The present study investigated the effects of Mda-7/IL-24 overexpression on the sensitivity of human B cell lymphoma cells to chemotherapy, as well as its mechanism of action. The sensitivity of stable Mda-7/IL-24 overexpressing Raji and Daudi cells to cis-diamminedichloroplatinum (CDDP), epirubicin and vinblastine (VCR) were assessed by the MTS method, and the IC 50 value calculated. Cell apoptosis and the intracellular accumulation of Rhodamine-123 were assayed by flow cytometry. The expression of multidrug resistance gene 1 (MDR1), B-cell-specific Moloney murine leukemia virus insertion site 1 (BMI1), topoisomerase II (Topo II) and multidrug resistance-related protein 1 (MRP1) mRNA and protein were analyzed by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blotting, respectively. In addition, western blot analysis was also used to investigate the effect of Mda-7/IL-24 on activity of GTP-RhoA-ERK signaling pathway in Raji and Daudi cells. Growth inhibition and apoptosis rates of Mda-7/IL-24 overexpressing Raji and Daudi cells were higher than those of non-transfected cells and cells transfected with vector alone when treated with CDDP, epirubicin and VCR. The IC 50 values of CDDP, epirubicin and VCR were lower for Mda-7/IL-24-overexpressing Raji and Daudi cells than for non-transfected cells and cells transfected with empty vector. Intracellular accumulation of Rhodamine-123 and the expression of Topo II were higher, while the levels of MDR1, BMI and MRP1 mRNA and protein were lower, in Mda-7/IL-24 overexpressing Raji and Daudi cells. Furthermore, the activities of GTP-RhoA-ERK signaling pathway in Raji and Daudi cells were suppressed. These results indicated that Mda-7/IL-24 enhanced the sensitivity of B lymphoma cells to chemotherapy agents by altering the expression of multidrug-resistance genes via downregulating GTP-RhoA-ERK signaling pathway, suggesting that treatment of B cell lymphomas with Mda-7/IL-24 could avoid MDR.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Mda-7/IL-24 enhances sensitivity of B cell lymphoma to chemotherapy drugs

Zhao

Sun

et al. 2016

Oncology Reports

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“…It was observed almost 10 years ago that P53 is a substrate for AMPK. In fact, P53 (via downstream proteins) significantly contributes to the overall response to gluconeogenesis and may induce autophagy (38-40). We subsequently determined whether phosphorylation was increased at these sites in MCF-7 cells exposed in cell culture to metformin (Supplementary Figure 3).…”

Section: Discussionmentioning

confidence: 99%

Lack of Effect of Metformin on Mammary Carcinogenesis in Nondiabetic Rat and Mouse Models

Thompson

Grubbs

Bode

et al. 2015

Cancer Prevention Research

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Epidemiologic studies have shown that diabetics receiving the biguanide metformin, as compared to sulfonylureas or insulin, have a lower incidence of breast cancer. Metformin increases levels of activated AMPK and decreases circulating IGF-1; encouraging its potential use in both cancer prevention and therapeutic settings. In anticipation of clinical trials in non-diabetic women, the efficacy of metformin in non-diabetic rat and mouse mammary cancer models was evaluated. Metformin was administered by gavage or in the diet, at a human equivalent dose, in standard mammary cancer models: (1) methylnitrosourea (MNU)-induced ER+ mammary cancers in rats, and (2) MMTV-Neu/P53KO ER- mammary cancers in mice. In the MNU rat model, metformin dosing (150 or 50 mg/Kg BW/day, by gavage) was ineffective in decreasing mammary cancer multiplicity, latency, or weight. Pharmacokinetic studies of metformin (150 mg/kg BW/day, by gavage) yielded plasma levels (Cmax and AUC) higher than humans taking 1.5 g/day. In rats bearing small palpable mammary cancers, short-term metformin (150 mg/kg BW/day) treatment increased levels of phospho-AMPK and phospho-p53 (Ser20) but failed to reduce Ki67 labeling or expression of proliferation-related genes. In the mouse model, dietary metformin (1500 mg/kg diet) did not alter final cancer incidence, multiplicity, or weight. Metformin did not prevent mammary carcinogenesis in two mammary cancer models; raising questions about metformin efficacy in breast cancer in non-diabetic populations.

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“…Other AIC biomarkers, including growth differentiating factors-15 (GDF-15), CBR1, AKR1A1 and AKR7A2 protein, and topoisomerase2β (Top2β) were studied in different populations and can also be used 15 16. In childhood cancer survivors GDF-15, a member of TGF superfamily, can be used as a marker of AIC 17.…”

Section: Discussionmentioning

confidence: 99%

Successful recovery and allogeneic stem cell transplant following chemotherapy-induced severe cardiomyopathy: literature review of management and prognostic factors

et al. 2016

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Chemotherapy-induced cardiomyopathy is one of the major possible hazards that can result from potential cardiotoxic agents while treating cancer. Prognostic risk factors include the rate of drug administration, history of hypertension, female gender, extremes of age, previous history of mediastinal irradiation, cumulative dose and pre-existing heart disease. Close monitoring of the patients, timely diagnosis, use of well-known biomarkers including cardiac troponins, NT-ProBNP and imaging studies like 2D Echo or cardiac MRI are essential. Emerging biomarkers include carbonyl reductases (CBR1 and CBR3), aldo-keto reductases (AKR, type 1A1, 1C3, 7A2) and topoisomerase2β (Top2β). β blockers and ACE inhibitors have not only been shown to slow down the progression of cardiac dysfunction but also produce symptomatic improvement. Our case report describes a patient with acute myeloblastic leukaemia who developed severe cardiomyopathy acutely after starting the anthracycline-based regimen. Nevertheless, with timely intervention her symptoms improved and subsequently she successfully received allogeneic stem cell transplantation.

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Topoisomerase II alpha expression and the Ki-67 labeling index correlate with prognostic factors in estrogen receptor-positive and human epidermal growth factor type-2-negative breast cancer

Cited by 25 publications

References 32 publications

Mda-7/IL-24 enhances sensitivity of B cell lymphoma to chemotherapy drugs

Mda-7/IL-24 enhances sensitivity of B cell lymphoma to chemotherapy drugs

Lack of Effect of Metformin on Mammary Carcinogenesis in Nondiabetic Rat and Mouse Models

Successful recovery and allogeneic stem cell transplant following chemotherapy-induced severe cardiomyopathy: literature review of management and prognostic factors

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