Mouse Models of Breast Cancer Share Amplification and Deletion Events with Human Breast Cancer

Breast tumor heterogeneity has been well documented through the use of multiplatform –omic studies in human tumors. However, there is no integrative database to capture the heterogeneity within mouse models of breast cancer. This project identifies genomic copy number alterations (CNAs) in 600 tumors across 27 major mouse models of breast cancer through the application of a predictive algorithm to publicly available gene expression data. It was found that despite the presence of strong oncogenic drivers in most mouse models, CNAs are extremely common but heterogeneous both between models and within models. Many mouse CNA events are largely conserved in human tumors and in the mouse we show that they are associated with secondary tumor characteristics such as tumor histology, metastasis, as well as enhanced oncogenic signaling. These data serve as an important resource in guiding investigators when choosing a mouse model to understand the gene copy number changes relevant to human breast cancer.     

A point prevalence survey of hospital inpatients to define the proportion with palliation as the primary goal of care and the need for specialist palliative care

The direct burden of people whose goal of care is a palliative approach has not been estimated in the acute care setting. Using a single time point, cross-sectional survey of all inpatient beds, an estimate was generated across a network of three South Australian public hospitals. One in three inpatients had a palliative approach as the goal of care and of these, only one in five had been referred to specialist palliative care services. Those referred were significantly more likely to have cancer and be younger men. Active recognition and documentation that a palliative approach frames the goals of care for this person needs to be incorporated more systematically into clinical practice in the acute care setting. At the same time, triggers for needs-based referral for specialist assessment should be implemented. Specialist palliative care services must also provide direct care for a wider range of patients than just those with cancer.     

A case report of tumor lysis syndrome after stage-one ALPPS

Rationale:Tumor lysis syndrome is a potentially lethal condition caused by rapid cell death, releasing a high level of toxic cytokines. It is common in patients with hematological malignancy but rare in solid tumors.Patient concerns:A 64-year-old patient presented to our unit with a 17.3-cm hepatocellular carcinoma and marginal liver reserve. The first-stage operation of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) was performed.Diagnosis:The patient was found to be anuric with grossly deranged electrolytes after the first-stage operation. Tumor lysis syndrome was diagnosed.Interventions:The patient was transferred to the intensive care unit for aggressive fluid administration and continuous venovenous hemofiltration for the management of tumor lysis syndrome.Outcomes:The patient recovered and then underwent the second-stage operation of ALPPS with extended right hepatectomy 8 days after the initial operation without any long-term sequelae.Lessons:ALPPS is a relatively new technique in liver surgery, entailing an increased risk of tumor lysis syndrome due to an in situ tumor after the first-stage operation. Clinicians should have a high index of suspicion regarding this potentially lethal complication with prompt management.     

Arginase Inhibition by Ethylacetate Extract of Caesalpinia sappan Lignum Contributes to Activation of Endothelial Nitric Oxide Synthase

Caesalpinia sappan (C. sappan) is a medicinal plant used for promoting blood circulation and removing stasis. During a screening procedure on medicinal plants, the ethylacetate extract of the lignum of C. sappan (CLE) showed inhibitory activity on arginase which has recently been reported as a novel therapeutic target for the treatment of cardiovascular diseases such as atherosclerosis. CLE inhibited arginase II activity prepared from kidney lysate in a dose-dependent manner. In HUVECs, inhibition of arginase activity by CLE reciprocally increased NOx production through enhancement of eNOS dimer stability without any significant changes in the protein levels of eNOS and arginase II expression. Furthermore, CLE-dependent arginase inhibition resulted in increase of NO generation and decrease of superoxide production on endothelium of isolated mice aorta. These results indicate that CLE augments NO production on endothelium through inhibition of arginase activity, and may imply their usefulness for the treatment of cardiovascular diseases associated with endothelial dysfunction.     

A mathematical algorithm for quantification of CT image noise

Quantification of computed tomography (CT) noise helps in determination of radiation dosage requirements for adequate image quality. Clinical methods used include calculation of the standard deviation (SD) of a selected region of interest (ROI). In industry, wavelet decomposition has been used for image compression while removing high‐frequency noise. We evaluated a cohort of 74 consecutive patients referred for coronary artery calcium scoring and quantitated noise within a 16×16 ROI in the ascending aorta using the traditional SD method and also using a two‐dimensional dyadic wavelet decomposition method. Clinically, noise has been shown to be proportional to patient weight and also body mass index (BMI), which is a derived value from height and weight. Noise for both methods was plotted against patient parameters of height, weight, waist circumference and calculated BMI. A regression line was calculated and coefficient of determination (CoD) calculated for each. The CoD was better for height, weight, and waist circumference using the wavelet method as compared to the traditional SD method. The wavelet method of quantification of image noise may be an improved method as compared to the SD method. This method could help further refine an imaging system's determination of radiation dosage requirements to obtain a satisfactory quality image.     

Up-regulation of ABCB1/P-glycoprotein by escaping promoter hypermethylation indicates poor prognosis in hematologic malignancy patients with and without bone marrow transplantation

We investigated the correlation between MDR1 promoter methylation status and MDR1 expression in 228 hematologic malignancies patients and 90 healthy controls. High level of MDR1 mRNA correlated to promoter hypomethylation and strongly associated with poor prognosis indicated by 2-year survival rates, poor CR rate (without BMT) and high relapse rate (with BMT). Furthermore, relative luciferase activity of methylated MDR1 at promoter −50 region was significantly higher than that of the unmethylated. In addition, MDR1 in K562 cells elevated significantly after 5-Aza-dC treatment. In summary, MDR1 promoter hypomethylation conferred its up-regulation and indicated poor prognosis in patients with and without BMT.     

Sudden unexpected death due to severe pulmonary and cardiac sarcoidosis

In this paper we report the autopsy findings of a 57 year old woman who died unexpectedly at home. She had been complaining of shortness of breath, episodes of dry coughing, and nausea. Her past medical and social history was unremarkable. She had no previous history of any viral or bacterial disease and no history of oncological disorders. Autopsy revealed multiple grayish-white nodular lesions in the pleura and epicardial fat and areas resembling fibrosis on the cut surface of the anterior and posterior wall of the left ventricle and interventricular septum. Histological examination of the lungs and heart revealed multiple well-formed noncaseating epithelioid cell granulomas with multinucleated giant cells. Death was attributed to myocardial ischemia due to vasculitis of intramural coronary artery branches associated with sarcoidosis. Sarcoidosis is a multisystemic disease of unknown etiology characterized by the formation of noncaseating epithelioid cell granulomas in the affected organs and tissues. The diagnosis of sarcoidosis in this case was established when other causes of granulomatous disease such as tuberculosis, berylliosis, hypersensitivity pneumonitis, and giant cell myocarditis had been reasonably excluded.     

Interstitial laser phototherapy assisted by magnetic resonance imaging: a new technique for monitoring laser-tissue interaction

The rapid technological advances of magnetic resonance imaging, laser fiberoptics, and compatible probes may allow treatment of deep and sometimes surgically unreachable tumors of the head and neck with minimal morbidity through interstitial laser phototherapy. In this study, a new application of magnetic resonance imaging was developed to monitor and quantify laser-induced tissue damages. Pig skin was exposed to increased levels of argon laser (514.5 nm) at energy densities between 62.5 and 375 J/cm2 as determined by an accurate and reproducible method of dosimetry. Thermal profiles were recorded using an infrared sensor and T1- and T2-weighted magnetic resonance images were taken; afterward, biopsies were performed to quantitate the level of tissue damage. Our results demonstrate that above a certain threshold of laser energy, the magnetic resonance imaging findings are temperature dependent. Appropriate development of a scale matching laser energies, temperature profiles, T1- and T2-weighted magnetic resonance images, and histological quantitation of tissue destruction will allow us to optimize the three-dimensional control and monitoring of laser-tissue interactions.