Implanted adipose progenitor cells as physicochemical regulators of breast cancer

Multipotent adipose-derived stem cells (ASCs) are increasingly used for regenerative purposes such as soft tissue reconstruction following mastectomy; however, the ability of tumors to commandeer ASC functions to advance tumor progression is not well understood. Through the integration of physical sciences and oncology approaches we investigated the capability of tumor-derived chemical and mechanical cues to enhance ASC-mediated contributions to tumor stroma formation. Our results indicate that soluble factors from breast cancer cells inhibit adipogenic differentiation while increasing proliferation, proangiogenic factor secretion, and myofibroblastic differentiation of ASCs. This altered ASC phenotype led to varied extracellular matrix (ECM) deposition and contraction thereby enhancing tissue stiffness, a characteristic feature of breast tumors. Increased stiffness, in turn, facilitated changes in ASC behavior similar to those observed with tumor-derived chemical cues. Orthotopic mouse studies further confirmed the pathological relevance of ASCs in tumor progression and stiffness in vivo. In summary, altered ASC behavior can promote tumorigenesis and, thus, their implementation for regenerative therapy should be carefully considered in patients previously treated for cancer.     

Efficacy of thymosin α-1 plus peginterferon α-2a combination therapy compared with peginterferon α-2a monotherapy in HBeAg-positive chronic hepatitis B: A prospective, multicenter, randomized, open-label study

Abstract Objective. Thymosin α-1 plus interferon α-2a offers superior efficacy over interferon α-2a alone in patients with chronic hepatitis B. The aim was to compare the antiviral efficacy of thymosin α-1 plus peginterferon α-2a and peginterferon α-2a alone in HBeAg-positive chronic hepatitis B patients. Materials and methods. HBeAg-positive CHB patients were enrolled in this prospective, randomized, open-label study. Fifty-one patients were assigned to either combination (26 patients; 180 μg of peginterferon α-2a weekly for 48 weeks and 1.6 mg of thymosin α-1 twice a week for the first 12 weeks) or monotherapy (25 patients; 180 μg of peginterferon α-2a weekly for 48 weeks) groups. Results. The rates of the combined response, defined as HBeAg seroconversion, HBV DNA suppression, and normalization of serum ALT, were 4/26 (15.4%) and 3/25 (12.0%) for the combination group and the monotherapy group at the end of treatment (p = 0.725), and 6/26 (23.1%) and 5/25 (20.0%) at the end of follow-up (p = 0.789), respectively. Based on multiple logistic regression analysis, a >2 log(10) IU/mL reduction of HBV DNA at week 12 was identified as an independent predictor for combined response (OR, 9.72; 95% CI, 1.33-71.06; p = 0.025) at the end of follow-up. A lower pretreatment HBV DNA level (≤7 log(10) IU/mL) was another predictor for combined response (OR, 9.64; 95% CI, 1.23-75.32; p = 0.031). No significant differences in adverse events were observed. Conclusions. The short-term addition of thymosin α-1 was not superior to peginterferon α-2a alone in HBeAg-positive CHB patients on the basis of antiviral efficacy.     

DNA cleavage and opening reactions of human topoisomerase IIα are regulated via Mg2+-mediated dynamic bending of gate-DNA

Topoisomerase II resolves intrinsic topological problems of double-stranded DNA. As part of its essential cellular functions, the enzyme generates DNA breaks, but the regulation of this potentially dangerous process is not well understood. Here we report single-molecule fluorescence experiments that reveal a previously uncharacterized sequence of events during DNA cleavage by topoisomerase II: nonspecific DNA binding, sequence-specific DNA bending, and stochastic cleavage of DNA. We have identified unexpected structural roles of Mg(2+) ions coordinated in the TOPRIM (topoisomerase-primase) domain in inducing cleavage-competent DNA bending. A break at one scissile bond dramatically stabilized DNA bending, explaining how two scission events in opposing strands can be coordinated to achieve a high probability of double-stranded cleavage. Clamping of the protein N-gate greatly enhanced the rate and degree of DNA bending, resulting in a significant stimulation of the DNA cleavage and opening reactions. Our data strongly suggest that the accurate cleavage of DNA by topoisomerase II is regulated through a tight coordination with DNA bending.     

Safety of dental extractions in coronary drug-eluting stenting patients without stopping multiple antiplatelet agents

Background:

The risk of excessive bleeding prompts physicians to stop multiple antiplatelet agents before minor surgery, which puts coronary stenting patients at risk for adverse thrombotic events.

Hypothesis:

We hypothesized that most dental extractions can be carried out safely without stopping multiple antiplatelet agents.

Methods:

All dental extraction patients who had undergone coronary stenting and who were also on oral multiple antiplatelet agents therapy were enrolled. One hundred patients underwent dental procedures without stopping antiplatelet agents. All wounds were sutured and followed up at 24 hours, 1 week, and 1 month after the procedure. There were 2233 patients who had not taken oral antiplatelet agents from a health promotion center and had teeth extracted by the same method. After performing propensity‐score matching for the entire population, a total of 100 matched pairs of patients were created. The primary outcome was a composite of excessive intraextraction blood loss, transfusion, and rehospitalization for bleeding, and the secondary outcome was a composite of death, nonfatal myocardial infarction, target lesion revascularization, and stent thrombosis within 1 month after the procedure.

Results:

There were 2 excessive intraextraction bleeding cases that continued at the extraction site for 4 and 5 hours, respectively, in the coronary stenting patients, and 1 excessive intraextraction bleeding case that continued for 3 hours in the control patients. There were no cases of transfusion, rehospitalization for bleeding, or major cardiovascular events for the 2 propensity‐matched groups.

Conclusions:

We found that most dental extractions in coronary stenting patients can be carried out safely without stopping multiple antiplatelet agents. The authors have no conflicts of interest to disclose. This study was supported in part by a grant from Yuhan Corporation, Ltd., Seoul, The Republic of Korea.     

The Impact of Stressor Patterns on Clinical Features in Patients With Tako‐tsubo Cardiomyopathy: Experiences of Two Tertiary Cardiovascular Centers

Background:

Tako‐tsubo cardiomyopathy (TTC) is typically triggered by an acute emotional or physical stress event. The aim of this study was to investigate the impact of stressor patterns on clinical features, laboratory parameters, and electrocardiographic and echocardiographic findings in patients with TTC.

Hypothesis:

Clinical features are different according to stressor patterns.

Methods:

Of 137 patients enrolled from the TTC registry database, 14 patients had emotional triggers (E group), 96 had physical triggers (P group), and 27 had no triggers (N group).

Results:

Most clinical presentations and in‐hospital courses were similar among the groups. However, the E group had a higher prevalence of chest pain (P = 0.006) and palpitation (P = 0.006), whereas the P group had a higher prevalence of cardiogenic shock (P = 0.040), than other groups. The P group had a significantly higher heart rate (P = 0.001); higher high‐sensitivity C‐reactive protein (P = 0.006), creatine kinase MB fraction (P = 0.045), and N terminal‐probrain natriuretic peptide (P = 0.036) levels; higher left ventricular end‐diastolic pressure (P = 0.019) and left ventricular end‐systolic diameter (P = 0.002); but lower left ventricular ejection fraction (P = 0.018). The E group had lesser prevalence of apical ballooning pattern (P = 0.038) than other groups. The P group required more frequent use of inotropics (P = 0.041) and diuretics (P = 0.047) and had significantly longer intensive care unit (P = 0.014) and in‐hospital stays (P = 0.001).

Conclusions:

The clinical features of TTC are different according to preceding stressor patterns. The TTC group with preceding physical stressors was less likely to have preserved cardiovascular reserve and more likely to require hemodynamic support than other groups. The overall prognosis of TTC is excellent, regardless of triggering stressors. Clin. Cardiol. 2011 DOI: 10.1002/clc.22053 The authors have no funding, financial relationships, or conflicts of interest to disclose.     

The Relationship Between Arterial Stiffness and Nonalcoholic Fatty Liver Disease

Aim  

Nonalcoholic fatty liver disease (NAFLD) is currently the most common form of chronic liver disease and some studies have documented its link with cardiovascular risk factors. This study aimed to investigate the association between arterial stiffness and NAFLD.