ATR inhibition sensitizes liposarcoma to doxorubicin by increasing DNA damage

Liposarcomas account for approximately 20% of all adult sarcomas and have limited therapeutic options outside of surgery. Inhibition of ataxia-telangiectasia and Rad3 related protein kinase (ATR) has emerged as a promising chemotherapeutic strategy in various cancers. However, its activation, expression, and function in liposarcoma remain unkown. In this study, we investigated the expression, function, and potential of ATR as a therapeutic target in liposarcoma. Activation and expression of ATR in liposarcoma was analyzed by immunohistochemistry, which was further explored for correlation with patient clinical characteristics. ATR-specific siRNA and the ATR inhibitor VE-822 were applied to determine the effect of ATR inhibition on liposarcoma cell proliferation and anti-apoptotic activity. Migration activity and clonogenicity were examined using wound healing and clonogenic assays. ATR (p-ATR) was overexpressed in 88.1% of the liposarcoma specimens and correlated with shorter overall survival in patients. Knockdown of ATR via specific siRNA or inhibition with VE-822 suppressed liposarcoma cell growth, proliferation, migration, colony-forming ability, and spheroid growth. Importantly, ATR inhibition significantly and synergistically enhanced liposarcoma cell line chemosensitivity to doxorubicin. Our findings support ATR as critical to liposarcoma proliferation and doxorubicin resistance. Therefore, the addition of ATR inhibition to a standard doxorubicin regimen is a potential treatment strategy for liposarcoma.     

Real Time Three-Dimensional Echocardiography for the Evaluation of Cardiomyopathy

Cardiomyopathy refers to a set of diseases that are characterized by myocardial dysfunction. Classically, two-dimensional echocardiography has been used in the diagnosis of these disorders and to help guide their management. Three-dimensional transthoracic echocardiography is now increasingly being used in the diagnosis, management, and prognostication of intrinsic cardiomyopathies. In this article, we summarize the available data on the use of three-dimensional transthoracic echocardiography in various forms of intrinsic cardiomyopathy as well as some of its advantages over traditional two-dimensional transthoracic echocardiography. (Echocardiography 2012;29:76-87)     

Book Review

Neurochemistry of the Aging Nervous System. A review of CNS Aging and its Neuropharmacology: Experimental and Clinical Aspects (Vol. 15, Interdisciplinary Topics in Gerontology), edited by W. Meier-Ruge. Basel, Switzerland: S. Karger, 1979. Pp. viii + 218, 45 illustrations, 30 tables, soft cover, ISBN: 3-8055-2980-5, $52.75.     

Assessment of the Fundamental Flexural Guided Wave in Cortical Bone by an Ultrasonic Axial-Transmission Array Transducer

The fundamental flexural guided wave (FFGW), as modeled, for example, by the A0 Lamb mode, is a clinically useful indicator of cortical bone thickness. In the work described in this article, we tested so-called multiridge-based analysis, based on the crazy climber algorithm and short-time Fourier transform, for assessment of the FFGW component recorded by a clinical array transducer featuring a limited number of elements. Methods included numerical finite-element simulations and experiments in bone phantoms and human radius specimens (n = 41). The proposed approach enabled extraction of the FFGW component and determination of its group velocity. This group velocity was in good agreement with theoretical predictions and possessed reasonable sensitivity to cortical width (r² = 0.51, p < 0.001) in the in vitro experiments. It is expected that the proposed approach enables related clinical application. Further work is still needed to analyze in more detail the challenges related to the impact of the overlying soft tissue.     

Psychosocial and Spiritual Care in Hospice: Differences Between Nursing,Social Work,and Clergy

A chart review of the most recent home visits from nursing, social work, and clergy to 37 home hospice patients indicated that all but two psychosocial and spiritual issues examined were addressed by hospice staff on home visits. Spirituality and, secondly, death anxiety were the most frequently discussed variables. Clergy addressed more spiritual issues than the other two professions, and social work addressed more psychosocial issues than the other two professions. These findings underscore the important roles that clergy and social work play on the hospice team, and imply that hospice should make a renewed commitment to psychosocial and spiritual care. [Article copies available for a fee from The Haworth Document Delivery Service: 1-800-342-9678. E-mail address: getinfo@haworth.com]     

Fractures of the lateral humeral condyle: role of the cartilage hinge in fracture stability.

This study investigates the hypothesis that the integrity of the cartilage hinge at the distal humeral epiphysis determines the stability of fractures of the lateral humeral condyle. Sixteen patients with lateral humeral condyle fractures were studied with radiographs and magnetic resonance imaging (MRI). The clinical course of each patient was compared using these imaging studies to determine whether initial fracture displacement and the integrity of the cartilage hinge correlated with fracture stability. Radiographically, 4 fractures were considered unstable (with initial fracture displacement >3 mm) and 12 were stable (initial displacement < or =3 mm). On MRI, 6 fractures were complete (with disruption of the lateral cartilage hinge) and 10 were incomplete. All unstable fractures had complete fractures on MRI. Ten of the 12 patients with radiographically stable injuries had incomplete fractures on MRI. None of these displaced during treatment. Two patients had radiographically stable fractures and complete fractures on MRI. One of these fractures displaced, confirming the hypothesis that the stability of lateral humeral condyle fractures is related to the integrity of the cartilage hinge.     

Natural orifice surgery: initial US experience utilizing the StomaphyXTM device to reduce gastric pouches after Roux-en-Y gastric bypass

Introduction

Weight gain after gastric bypass can occur in up to 10% of patients 5 years following and in about 20% of patients 10 years following surgery. The nadir weight is usually reached within the first 2 years after bypass surgery. However, weight may slowly be regained for numerous reasons. This phenomenon has been studied extensively, but there is often no one reason this occurs. Once psychological and dietary reasons have been investigated, revisional surgery may be the only alternative for treatment. Revisional gastric bypass surgery is associated with a much higher morbidity and mortality when compared with a primary gastric bypass procedure.

Patients and methods

Thirty-nine patients underwent endoluminal gastric pouch reduction with the StomaphyX^TM device after informed consent. The StomaphyX^TM device is a sterile, single-use device for use in endoluminal transoral tissue approximation and ligation in the gastrointestinal (GI) tract.

Results

Average age was 47.8 (29–64) years, and 36/39 (92.3%) patients were female. Average body mass index (BMI) and weight prior to the StomaphyX^TM procedure were 39.8 (22.7–63.2) kg/m² and 108.0 kg (65.90–172.2 kg). The average preprocedure excess body weight was 51.1 kg. Weight loss at 2 weeks (n = 39) was 3.8 kg (7.4% excess body weight loss, EBWL), at 1 month (n = 34) was 5.4 kg (10.6% EBWL), at 2 months (n = 26) was 6.7 kg (13.1% EBWL), at 3 months (n = 15) was 6.7 kg (13.1% EBWL), at 6 months (n = 14) was 8.7 kg (17.0% EBWL), and at 1 year (n = 6) was 10.0 kg (19.5% EBWL). No major complications were observed. The minor complications that were seen included a sore throat lasting less than 48 h in 34/39 patients (87.1%) and epigastric pain that lasted for a few days in 30/39 patients (76.9%). Three patients with chronic diarrhea had their symptoms resolved after the procedure. Eight patients with gastroesophageal reflux disease reported improvement in their symptoms post procedure.

Conclusions

Endoluminal revision of gastric bypass patients with weight gain using the StomaphyX^TM procedure may offer an alternative to open or laparoscopic revisional bariatric surgery.