Dietary Intake and Serum Levels of Iron in Relation to Oxidative Stress in Breast Cancer Patients

Iron may induce oxidative stress via production of reactive oxygen species, facilitating mammary carcinogenesis. This study investigated the role of iron in relation to oxidative stress as a potential risk factor in the development of breast cancer (BC). BC patients (n = 121) and healthy age-matched controls (n = 149) were entered into the study. Iron and antioxidant vitamins intakes were estimated using a quantitative food frequency questionnaire. Thirty one subjects from each group provided blood samples for measurement of serum iron, plasma malondialdehyde (MDA) and ferric reducing ability of plasma (FRAP). Total and non-heme iron intake of BC patients were lower than those of the controls. However, the serum iron level was significantly higher in BC patients. Plasma MDA levels were also significantly higher in BC patients whereas no significant difference in FRAP values were observed between the two groups. Log-transformed serum iron concentration showed no significant correlation with MDA or FRAP. These results suggest that serum iron overload may be a breast cancer risk factor possibly due to increased oxidative stress

Additive Value of B-Type Natriuretic Peptide on Rest 201Tl-Dipyridamole Stress 99mTc-Sestamibi Gated Myocardial SPECT in Patients with Normal Left Ventricular Systolic Function

We evaluated whether BNP has additive value to SPECT in patients with normal left ventricular (LV) systolic function. Data from 224 consecutive patients who underwent rest 201Tl-dipyridamole stress 99mTc-sestamibi gated SPECT and coronary angiography due to chest pain were analyzed. Patients with true positive SPECT showed significant higher BNP level than those with false positive defect (38.5 (19.0–79.8) versus 19.0 (9.3–35.8), P = .01). Patients with true negative SPECT also showed significantly lower BNP level than those with false negative SPECT (39.0 (23.0–77.0) versus 22.0 (15.0–43.0), P = .002). In multivariate analyses, elevated BNP level (using a cut-off value of 23.0 pg/mL) was the strongest and independent predictor of CAD in overall patients (OR 2.75, 95% CI: 1.50–5.023, P = .001) and patients with positive SPECT (OR 3.34, 95% CI: 1.51–7.37, P = .003). The area under the receiver-operating characteristic curve for CAD in overall patients and patients with positive SPECT was 0.673 (95% CI: 0.603–0.743, P < .001) and 0.694 (95% CI: 0.602–0.786, P < .001), respectively. This study suggests that BNP level has additive diagnostic value to SPECT findings in predicting CAD in patients with normal LV systolic function

Titanium dioxide nanoparticles enhance thrombosis through triggering the phosphatidylserine exposure and procoagulant activation of red blood cells

Background Expanding biomedical application of anatase titanium dioxide (TiO2) nanoparticles (NPs) is raising the public concern on its potential health hazards. Here, we demonstrated that TiO2 NPs can increase phosphatidylserine (PS) exposure and procoagulant activity of red blood cells (RBCs), which may contribute to thrombosis. Results We conducted in vitro studies using RBCs freshly isolated from healthy male volunteers. TiO2 NPs exposure (≦ 25 μg/mL) induced PS exposure and microvesicles (MV) generation accompanied by morphological changes of RBCs. While ROS generation was not observed following the exposure to TiO2 NPs, intracellular calcium increased and caspase-3 was activated, which up-regulated scramblase activity, leading to PS exposure. RBCs exposed to TiO2 NPs could increase procoagulant activity as measured by accelerated thrombin generation, and enhancement of RBC-endothelial cells adhesion and RBC-RBC aggregation. Confirming the procoagulant activation of RBC in vitro, exposure to TiO2 NPs (2 mg/kg intravenously injection) in rats increased thrombus formation in the venous thrombosis model. Conclusion Collectively, these results suggest that anatase TiO2 NPs may harbor prothrombotic risks by promoting the procoagulant activity of RBCs, which needs attention for its biomedical application.This research was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea Government (MSIP) (2015R1A2A2A01011705), National Natural Science Foundation of China (No.82020108027 and No.82003500) as well as the Talent Introduction Program of Postdoctoral International Exchange Program (No. YJ20190263)

Chfr is linked to tumour metastasis through the downregulation of HDAC1

Chfr is a ubiquitin ligase that functions in the mitotic checkpoint by delaying entry into metaphase in response to mitotic stress. It has been suggested that Chfr is a tumour suppressor as Chfr is frequently silenced in human cancers. To better understand how Chfr activity relates to cell-cycle progression and tumorigenesis, we sought to identify Chfr-interacting proteins using affinity purification combined with mass spectrometry. Histone deacetylase 1 (HDAC1), which represses transcription by deacetylating histones, was newly isolated as a Chfr-interacting protein. Chfr binds and downregulates HDAC1 by inducing its polyubiquitylation, both in vitro and in vivo. Ectopic expression of Chfr in cancer cells that normally do not express it results in downregulation of HDAC1, leading to upregulation of the Cdk inhibitor p21^(CIP1/WAF1) and the metastasis suppressors KAI1 and E-cadherin. Coincident with these changes, cells arrest in the G1 phase of the cell cycle and become less invasive. Collectively, our data suggest that Chfr functions as a tumour suppressor by regulating HDAC1

Reversible Proximal Renal Tubular Dysfunction after One-Time Ifosfamide Exposure

The alkylating agent ifosfamide is an anti-neoplastic used to treat various pediatric and adult malignancies. Its potential urologic toxicities include glomerulopathy, tubulopathy and hemorrhagic cystitis. This report describes a case of proximal renal tubular dysfunction and hemorrhagic cystitis in a 67-year-old male given ifosfamide for epitheloid sarcoma. He was also receiving an oral hypoglycemic agent for type 2 diabetes mellitus and had a baseline glomerular filtration rate of 51.5 mL/min/1.73 m2. Despite mesna prophylaxis, the patient experienced dysuria and gross hematuria after a single course of ifosfamide plus adriamycin. The abrupt renal impairment and serum/urine electrolyte imbalances that ensued were consistent with Fanconi's syndrome. However, normal renal function and electrolyte status were restored within 14 days, simply through supportive measures. A score of 8 by Naranjo adverse drug reaction probability scale indicated these complications were most likely treatment-related, although they developed without known predisposing factors. The currently undefined role of diabetic nephropathy in adult ifosfamide nephrotoxicity merits future investigation

Complete biologic response to taxane based chemotherapy confirmed by [18F]FDG PET/CT and surgery in a cancer of unknown primary site

Cancers of an unknown primary site are heterogenous with respect to their clinical and pathologic features. They are generally very aggressive, but specific favorable subsets have a better prognosis. For these favorable subsets, taxane based chemotherapy is very effective for a subset of woman with papillary serous peritoneal adenocarcinoma. A 52 year-old woman underwent [18F]-FDG PET/CT for routine health screening. On PET/CT, multiple hypermetabolic lymph nodes were detected in the paraaortic spaces, and there were no other hypermetabolic abnormalities. The patient was diagnosed with an unknown primary cancer that probably originated from the ovary or peritoneum, according to clinical studies and biopsy results. This was not a typical case of a favorable subset of cancer of an unknown primary site, but the tumor showed complete biologic response to taxane based chemotherapy as revealed by PET/CT, and necrotic tumor cells were confirmed by surgery

Clinical Characteristics of Coronary Drug-Eluting Stent Fracture: Insights from a Two-Center DES Registry

Stent fracture (SF) has been implicated as a risk factor for in-stent restenosis, but its incidence and clinical characteristics are not well established. Therefore we investigated the conditions associated with stent fracture and its clinical presentation and outcome. Between 2004 and 2007, consecutive cases of SF were collected from the Seoul National University Hospital. Clinical characteristics and outcome of patients with fractured stents were compared with a ten-fold cohort of age and gender matched controls (n = 236). A total of 4,845 patients received percutaneous coronary intervention and 3,315 patients (68.4%) underwent angiographic follow-up. Twenty-eight fractured stents were observed in 24 patients. The incidence of SF was 0.89% for sirolimus-eluting stents (SES) and 0.09% for paclitaxel-eluting stents. Chronic kidney disease, stent implantation in the right coronary artery (RCA), and SES use were independent predictors of drug-eluting stent fracture by multivariate analysis. SF was significantly associated with binary restenosis (11.4% vs 41.7%, P < 0.001) and increased risk of target lesion revascularization (8.1% vs 33.3%, P = 0.001). Patients with SF but without significant restenosis showed excellent outcome despite only medical treatment. In conclusion, SF is associated with increased rates of restenosis and repeat revascularization. Significant risk factors include chronic kidney disease, RCA intervention, and SES use