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Harry Feld Paul Nathan Dilsukh Raninga Jacob Shani 《Catheterization and cardiovascular interventions》1992,26(1):12-14
Subclavian artery stenosis causing severely symptomatic angina in a patient with a previous left internal mammary artery bypass to the left anterior descending artery was treated successfully with percutaneous transluminal angioplasty. Baseline arteriography clearly revealed subclavian and coronary steal by evidence of competitive flow of nonopacified blood from the left vertebral artery. Although there was a difference of only 15 mm Hg between the right and left brachial arteries, there was a palpable difference in the upstroke of these pulses. The stenosis in the subclavian artery was successfully dilated with percutaneous transluminal angioplasty. Angiographic evidence of subclavian steal resolved following balloon dilatation, and the patient's angina was completely resolved. © 1992 Wiley-Liss, Inc. 相似文献
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Prahlad V. Raninga Andy C. Lee Debottam Sinha Yu-Yin Shih Deepak Mittal Ashwini Makhale Amanda L. Bain Devathri Nanayakarra Kathryn F. Tonissen Murugan Kalimutho Kum Kum Khanna 《International journal of cancer. Journal international du cancer》2020,146(1):123-136
Triple-negative breast cancer (TNBCs) is a very aggressive and lethal form of breast cancer with no effective targeted therapy. Neoadjuvant chemotherapies and radiotherapy remains a mainstay of treatment with only 25–30% of TNBC patients responding. Thus, there is an unmet clinical need to develop novel therapeutic strategies for TNBCs. TNBC cells have increased intracellular oxidative stress and suppressed glutathione, a major antioxidant system, but still, are protected against higher oxidative stress. We screened a panel of antioxidant genes using the TCGA and METABRIC databases and found that expression of the thioredoxin pathway genes is significantly upregulated in TNBC patients compared to non-TNBC patients and is correlated with adverse survival outcomes. Treatment with auranofin (AF), an FDA-approved thioredoxin reductase inhibitor caused specific cell death and impaired the growth of TNBC cells grown as spheroids. Furthermore, AF treatment exerted a significant in vivo antitumor activity in multiple TNBC models including the syngeneic 4T1.2 model, MDA-MB-231 xenograft and patient-derived tumor xenograft by inhibiting thioredoxin redox activity. We, for the first time, showed that AF increased CD8+Ve T-cell tumor infiltration in vivo and upregulated immune checkpoint PD-L1 expression in an ERK1/2-MYC-dependent manner. Moreover, combination of AF with anti-PD-L1 antibody synergistically impaired the growth of 4T1.2 primary tumors. Our data provide a novel therapeutic strategy using AF in combination with anti-PD-L1 antibody that warrants further clinical investigation for TNBC patients. 相似文献
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Prahlad V. Raninga Giovanna Di Trapani Slavica Vuckovic Maneet Bhatia Kathryn F. Tonissen 《Oncotarget》2015,6(17):15410-15424
Multiple myeloma (MM) is a hematological malignancy characterized by the aberrant accumulation of clonal plasma cells in the bone marrow. Despite recent advancement in anti-myeloma treatment, MM remains an incurable disease. This study showed higher intrinsic oxidative stress and higher Trx1 and TrxR1 protein levels in MM cells compared to normal cells. Drug-induced Trx1 (PX-12) and TrxR1 (Auranofin) inhibition disrupted redox homeostasis resulting in ROS-induced apoptosis in MM cells and a reduction in clonogenic activity. Knockdown of either Trx1 or TrxR1 reduced MM cell viability. Trx1 inhibition by PX-12 sensitized MM cells to undergo apoptosis in response to the NF-кβ inhibitors, BAY 11-7082 and curcumin. PX-12 treatment decreased the expression of the NF-кβ subunit p65 in MM cells. Bortezomib-resistant MM cells contained higher Trx1 protein levels compared to the parental cells and PX-12 treatment resulted in apoptosis. Thus, increased Trx1 enhances MM cell growth and survival and exerts resistance to NF-кβ inhibitors. Therefore inhibiting the thioredoxin system may be an effective therapeutic strategy to treat newly diagnosed as well as relapsed/refractory MM. 相似文献
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Subclavian artery stenosis causing severely symptomatic angina in a patient with a previous left internal mammary artery bypass to the left anterior descending artery was treated successfully with percutaneous transluminal angioplasty. Baseline arteriography clearly revealed subclavian and coronary steal by evidence of competitive flow of nonopacified blood from the left vertebral artery. Although there was a difference of only 15 mm Hg between the right and left brachial arteries, there was a palpable difference in the upstroke of these pulses. The stenosis in the subclavian artery was successfully dilated with percutaneous transluminal angioplasty. Angiographic evidence of subclavian steal resolved following balloon dilatation, and the patient's angina was completely resolved. 相似文献
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