Tumor–microenvironment interactions studied by zonal transcriptional profiling of squamous cell lung carcinoma

Invasion is a critical step in lung tumor progression. The interaction between tumor cells and their surroundings may play an important role in tumor invasion and metastasis. To better understand the mechanisms of tumor invasion and tumor–microenvironment interactions in lung tumors, total RNA was isolated from the inner tumor, tumor invasion front, adjacent lung, and distant normal lung tissue from 17 patients with primary squamous cell lung carcinoma using punch‐aided laser capture microdissection. Messenger RNA expression profiles were obtained by microarray analysis, and microRNA profiles were generated from eight of these samples using TaqMan Low Density Arrays. Statistical analysis of the expression data showed extensive changes in gene expression in the inner tumor and tumor front compared with the normal lung and adjacent lung tissue. Only a few genes were differentially expressed between tumor front and the inner tumor. Several genes were validated by immunohistochemistry. Evaluation of the microRNA data revealed zonal expression differences in nearly a fourth of the microRNAs analyzed. Validation of selected microRNAs by in situ hybridization demonstrated strong expression of hsa‐miR‐196a in the inner tumor; moderate expression of hsa‐miR‐224 in the inner tumor and tumor front, and strong expression of hsa‐miR‐650 in the adjacent lung tissue. Pathway analysis placed the majority of genes differentially expressed between tumor and nontumor cells in intrinsic processes associated with inflammation and extrinsic processes related to lymphocyte physiology. Genes differentially expressed between the inner tumor and the adjacent lung/normal lung tissue affected pathways of arachidonic acid metabolism and eicosanoid signaling. © 2012 Wiley Periodicals, Inc.     

Does footwear affect articular cartilage volume change after a prolonged run?

The aim of this study was to investigate knee intra-articular cartilage volume changes after a prolonged running bout in three footwear conditions. Twelve participants performed 75-minute running bouts in the three footwear conditions. Before and after each running bout, magnetic resonance imaging (MRI) scans were obtained using a high-resolution 3.0 Tesla MRI. Three-dimensional reconstruction of the cartilage plates of the patella, the femur, and the tibia was created to quantify cartilage volume change due to the 75-minute running bout. Three-dimensional biomechanical data were also collected using an integrated motion capture and force treadmill system. There were no statistically significant differences among shoe conditions for all anatomical regions. However, significant cartilage volume reductions at all anatomical sites were observed after the 75-minute running bout in each footwear condition. These data suggest that the intra-articular knee cartilage undergoes a significant reduction in cartilage volume during a prolonged run that may indicate an increase in joint loading. There was a considerable variation in cartilage volume between participants across footwear conditions indicating an individual cartilage volume response to footwear. An individualistic approach to footwear recommendations may help in minimizing this change in cartilage.     

Highly flexible nitinol mesh to encase aortocoronary saphenous vein grafts: first clinical experiences and angiographic results nine months postoperatively

Saphenous vein graft patency is frequently limited by degeneration. Experimental studies have indicated that rigid external support of venous grafts by a flexible, tubular nitinol mesh may improve graft patency. The study presented was part of a prospective, randomized, multicenter first-in-man trial investigating the safety and effectiveness of nitinol-supported venous grafts in coronary artery bypass graft (CABG) surgery. From our clinic, 25 subjects with multivessel coronary artery disease requiring saphenous vein graft CABG of the right coronary artery (RCA) and the circumflex artery were entered into the trial. Subjects were randomized to receive a mesh-supported graft on one of these arteries; the other vessel received an untreated vein graft. Graft patency was assessed by coronary angiography nine months after surgery. The implantation of mesh grafts was simple and safe. In 10 cases, a nitinol mesh-supported venous graft was anastomosed to the circumflex artery and in 15 cases to the RCA. All patients survived the observation period. A total of 72% of the patients underwent control coronary angiography. The patency rate of mesh-supported grafts was 27.8% nine months postoperatively. Conventional vein grafts showed an 85.7% patency, and arterial grafts had a 100% patency. No complications directly related to the implantation of mesh-supported grafts were observed. The promising experimental results of mesh-supported venous grafts could not be reproduced in the study presented. A critical item seems to be correct selection of nitinol mesh diameter, the anastomotic method and fixation of the mesh tube to the venous graft.     

Expandable metal stents for malignant hilar biliary obstruction

Most patients with malignant hilar stenoses are candidates for palliation. For this purpose, biliary drainage plays a major role in improving liver function and managing or avoiding cholangitis. Endoscopic interventions are less invasive than the percutaneous approach and should be considered as the first-line drainage procedures in most cases. Transhepatic interventions should be reserved for endoscopic failures or performed as a complementary approach in a combined procedure. After successful endoscopic access to biliary obstruction, implantation of self-expandable metal stents offers advantages over plastic endoprostheses in terms of stent patency and number of reinterventions.     

Detection of chromosomal imbalances in retinoblastoma by matrix-based comparative genomic hybridization

The genetic hallmark of retinoblastoma is mutation or deletion of the RB1 gene, whereas other genetic alterations that are also required are largely unknown. To screen for genomic imbalances on a genomewide level, we studied a series of 17 primary retinoblastomas by matrix-based comparative genomic hybridization (matrix-CGH). The matrix-CGH chip contained 6,000 immobilized genomic DNA fragments covering the human genome, with an average resolution of about 500 kb. The most frequent imbalances detected were gains on chromosome arms 1q (12 of 17), 6p (10 of 17), 2p (5 of 17), and 19q (4 of 17) and loss on 16q (7 of 17). Candidate regions could be narrowed to small intervals by the identified minimally overlapping regions on 1q22, 1q32.1q32.2, 2p24.1, and 6p21.33-p21.31. Furthermore, two as-yet-unknown high-level amplifications were detected, each in a single patient, on chromosome bands 1p34.2 and 1p33. Thus, this study identified new chromosomal regions and therefore potential candidate genes that may play a role in retinoblastoma.     

Prostaglandin E2 induces vasodilation and pruritus,but no protein extravasation in atopic dermatitis and controls

BACKGROUND: Prostaglandin E(2) (PGE(2)) has well-established vasodilatory effects, whereas its effects on protein extravasation and its sensory effects are less clear. OBJECTIVE: Vasoactive effects of PGE(2) were correlated to its ability to evoke pain or itch in healthy volunteers and patients with atopic dermatitis (AD). METHODS: Intradermal microdialysis was used to apply PGE(2) (10(-8)-10(-4) M) via microdialysis capillaries in 8 patients and 8 controls. Large pore size membranes (3000 kd) enabled simultaneous analysis of protein extravasation. Itch and pain sensations were measured psychophysically, and superficial blood flow was measured by laser Doppler imaging. RESULTS: PGE(2) dose dependently provoked intense local vasodilation, weak pruritus, and pain, but no protein extravasation. No differences were found between patients with AD and controls for any parameter. CONCLUSION: We conclude that PGE(2) is a potent vasodilator and a weak pruritic agent in normal skin and in patients with AD, but does not provoke increased protein extravasation.