Matrix detachment and proteasomal inhibitors diminish Sulf-2 expression in breast cancer cell lines and mouse xenografts

Sulfatase 2 (Sulf-2) has been previously shown to be upregulated in breast cancer. Sulf-2 removes sulfate moieties on heparan sulfate proteoglycans which in turn modulate heparin binding growth factor signaling. Here we report that matrix detachment resulted in decreased Sulf-2 expression in breast cancer cells and increased cleavage of poly ADP-ribose polymerase. Silencing of Sulf-2 promotes matrix detachment induced cell death in MCF10DCIS cells. In an attempt to identify Sulf-2 specific inhibitor, we found that proteasomal inhibitors such as MG132, Lactacystin and Bortezomib treatment abolished Sulf-2 expression in multiple breast cancer cell lines. Additionally, we show that Bortezomib treatment of MCF10DCIS cell xenografts in mouse mammary fat pads significantly reduced tumor size, caused massive apoptosis and more importantly reduced Sulf-2 levels in vivo. Finally, our immunohistochemistry analysis of Sulf-2 expression in cohort of patient derived breast tumors indicates that Sulf-2 is significantly upregulated in autologous metastatic lesions compared to primary tumors (p < 0.037, Pearson correlation, Chi-Square analysis). In all, our data suggest that Sulf-2 might play an important role in breast cancer progression from ductal carcinoma in situ into an invasive ductal carcinoma potentially by resisting cell death.     

Ventricular arrhythmias and left ventricular myocardial function in chronic chagasic patients

To study the relationship of complex ventricular arrhythmias to the presence and extent of myocardial damage, 556 chronic chagasic patients were submitted to an extensive protocol, including left ventricular cineangiography and Holter monitoring, and properly classified according to clinical, electrocardiographic and hemodynamic findings. Stages of the clinical-hemodynamic classification corresponded to increasing degrees of myocardial damage, age, prevalence and complexity of ventricular arrhythmias. Myocardial damage (particularly left ventricular dilatation) was the most important clinical factor linked to the presence of complex ventricular arrhythmias. A clear difference in terms of ventricular function was found only when arrhythmias were grouped into simple (Lown grades I and II) and complex (grades III and IV) forms. It is recommended that any classification for chagasic patients must be based on signs of myocardial involvement, instead of clinical or electrocardiographic findings alone. Evaluation should include accurate determination of left ventricular myocardial function, along with the search for the presence of complex ventricular arrhythmias and abnormalities of conduction.     

Successful treatment of pulmonary mucormycosis in an allogenic bone-marrow transplant recipient with combined medical and surgical therapy

Mucormycosis is a rare, but severe, complication in allogenic bone-marrow recipients with a mortality rate of about 80%. Moreover, its incidence appears to have increased within the last decade. We report a case of pulmonary and nasal mucormycosis in a 55-y-old patient, which occurred 1 y after BMT. Treatment combining 4 months of amphotericin B, early surgical resection of infected tissue and discontinuation of immunosuppressive treatment allowed the cure of this mould infection.     

Small-diameter (2 mm) laparoscopy in the evaluation of liver disease

Background: Percutaneous liver biopsy fails to demonstrate cirrhosis in approximately 32% of cases when compared with laparoscopy with liver biopsy. The aim of this study is to determine the usefulness of small-diameter (2 mm) laparoscopes compared with larger laparoscopes. Methods: Patients undergoing diagnostic laparoscopy for various liver diseases were evaluated with small-diameter (2 mm) laparoscopes either alone or in combination with a 5 or 10 mm laparoscope. Results: Twenty patients were enrolled in this study. Small-diameter laparoscopes provided appropriate visualization of the abdominal organs and proper guidance to liver biopsy in 9 cases. In the remaining 11 cases a larger laparoscope was used for the following reasons: short length of the trocar/introducer in a morbidly obese patient (1), liver mass located in the anterosuperior aspect of the liver precluding good visualization with forward lenses (1), and inability to properly visualize the anterosuperior aspect of the liver (9). No complications were noted with the use of the small-diameter laparoscopes alone. Conclusion: There is a need for an oblique-viewing minilaparoscope that allows visualization comparable to the larger laparoscopes.     

The Relationship Between Renal Resistive Index,Arterial Stiffness,and Atherosclerotic Burden: The Link Between Macrocirculation and Microcirculation

The renal resistive index (RRI) measured by Doppler sonography is a marker of microvascular status that can be generalized to the whole of the arterial tree. Its association with large‐vessel dysfunction, such as arterial stiffness or the atherosclerotic burden, can help to establish physiopathological associations between macrocirculation and microcirculation. The authors conducted a cross‐sectional study of hypertensive patients (n=202) and a healthy control group (n=16). Stiffness parameters, atherosclerotic burden, and determination of the RRI in both kidneys were performed. The average RRI was 0.69±0.08 and was significantly greater in patients with diabetes and chronic kidney disease. Renal resistive index positively correlated with age, creatinine, and albuminuria. Positive correlations were found with arterial stiffness parameters (pulse wave velocity, ambulatory arterial stiffness index, and 24‐hour pulse pressure), as well as atherosclerotic burden and endothelial dysfunction measured as asymmetric dimethylarginine in serum. In the multivariate analysis, independent factors for increased RRI were age, renal function, 24‐hour diastolic blood pressure, and arterial stiffness. The authors concluded that there is an independent association between renal hemodynamics and arterial stiffness. This, together with the atherosclerotic burden and endothelial dysfunction, suggests that there is a physiopathologic relationship between macrovascular and microvascular impairment.