Unravelling the complexity of metastasis - molecular understanding and targeted therapies

Despite recognizing the devastating consequences of metastasis, we are not yet able to effectively treat cancer that has spread to vital organs. The inherent complexity of genomic alterations in late-stage cancers, coupled with numerous heterotypic interactions that occur between tumour and stromal cells, represent fundamental challenges in our quest to understand and control metastatic disease. The incorporation of genomic and other systems level approaches, as well as technological breakthroughs in imaging and animal modelling, have galvanized the effort to overcome gaps in our understanding of metastasis. Future research carries with it the potential to translate the wealth of new knowledge and conceptual advances into effective targeted therapies.     

Tumor-derived JAGGED1 promotes osteolytic bone metastasis of breast cancer by engaging notch signaling in bone cells

Despite evidence supporting an oncogenic role in breast cancer, the Notch pathway's contribution to metastasis remains unknown. Here, we report that the Notch ligand Jagged1 is a clinically and functionally important mediator of bone metastasis by activating the Notch pathway in bone cells. Jagged1 promotes tumor growth by stimulating IL-6 release from osteoblasts and directly activates osteoclast differentiation. Furthermore, Jagged1 is a potent downstream mediator of the bone metastasis cytokine TGFβ that is released during bone destruction. Importantly, γ-secretase inhibitor treatment reduces Jagged1-mediated bone metastasis by disrupting the Notch pathway in stromal bone cells. These findings elucidate a stroma-dependent mechanism for Notch signaling in breast cancer and provide rationale for using γ-secretase inhibitors for the treatment of bone metastasis.     

Secondary cold agglutinin disease associated with Hashimoto disease

Our case involves a 53 year old woman. Three years ago, she was investigated because of normal hemoglobin levels despite very a low erythrocyte count, which was revealed during the preoperative evaluation for ovarian cyst operation. The Direct Coombs test was found to be positive against complement and negative against IgG. Cold agglutinin titer was 1/448 (+). Due to the polyclonal IgM increase, secondary cold agglutinin disease (CAD) was considered but no factor could be found that would lead to cold agglutinin disease. During the post-operative follow-up, cold agglutinin titers increased with fluctuations in the patient. Twenty-four months after transabdominal hysterectomy and bilateral salpingooopherectomy operation, diagnosis of Hashimoto disease was made upon detection of subclinical hypothyroidism. No case of Hashimoto disease associated with CAD caused by polyclonal IgM has been reported until the present time.     

Right and left ventricular adaptation to training determined by conventional echocardiography and tissue Doppler imaging in young endurance athletes

OBJECTIVE: Some findings of left ventricular (LV) functions in athletes are controversial. On the other hand, studies concerning the right ventricle (RV) are limited. The aim of the study was to assess the effects of endurance training on LV and RV systolic and diastolic function. METHODS: A total of 60 (54 male, 6 female) athletes (mean age 20.7 +/- 2.5 years) and 60 (51 male, 9 female) healthy subjects (mean age 21.3 +/- 2.6 years) were included in the study. Standard echocardiographic examination and pulsed wave Doppler and tissue Doppler imaging (TDI) were performed. RESULTS: Except LV and RV ejection fraction, all M-mode echocardiographic parameters of the athletes were found to be significantly greater compared to untrained subjects. LV cavity dimension enlarged (> 55 mm) in 23 (38.4%) athletes but none of the controls. Of 54 male and 6 female athletes 33 (61.1%) and 5 (83.3%) had left vantricular hypertrophy. Athletes also had a greater RV free-wall thickness and mass index. None of the control subjects had either LV or RV hypertrophy. The mean LVMI/RVMI ratio was 3.77 +/- 1.59 and 3.40 +/- 1.32 in athletes and controls, respectively (p = 0.5). The mean E/A and Em/Am ratios and Sm velocities of both ventricles were significantly higher in athletes compared to untrained subjects (p < 0.001). CONCLUSION: Our study shows that despite an increase in left and right ventricular mass indexes, the LVMI/RVMI ratio stays stable. Training results in a better systolic and diastolic function.     

Gastric perforation in an extremely low birth weight infant recovered with percutaneous peritoneal drainage

Neonatal gastric perforation is an uncommon but life-threatening condition, which is mainly encountered in premature infants. Primary surgical repair is the principal mode of the treatment. Gastric perforation in neonates improving with percutaneous peritoneal drainage alone has not been described previously. Therefore, an extremely low birth weight infant is presented herein in order to emphasize that gastric perforation may improve with percutaneous peritoneal drainage alone. Isolated gastric perforations in newborn infants may be improved with percutaneous peritoneal drainage alone without need for primary surgical repair.     

Comparison of iodine-125 plaque brachytherapy and gamma knife stereotactic radiosurgery treatment outcomes for uveal melanoma patients

Graefe's Archive for Clinical and Experimental Ophthalmology - To compare the efficacies of iodine-125 brachytherapy (IBT) and gamma knife stereotactic radiosurgery (GKRS) in the treatment of...