Novel applications of an injectable radiopaque hydrogel tissue marker for management of thoracic malignancies.

Background: Radiopaque markers (otherwise known as fiducials) are used clinically to mark sites of biopsy or resection, which aids with targeting of local therapy, including surgery and radiation therapy. We performed a human cadaveric imaging series with a novel, injectable, radiopaque, absorbable hydrogel marker to demonstrate its potential in the management of thoracic malignancies.

Methods: Baseline CT imaging was performed on three unfixed cadaveric specimens.

Human immunodeficiency virus infection as a prognostic factor in surgical patients with non-small cell lung cancer.

Background: The purpose of this study was to assess the effect of human immunodeficiency virus (HIV) infection on postoperative survival among non-small cell lung cancer (NSCLC) patients.

Methods: A retrospective cohort study compared 22 HIV-infected lung cancer patients to 2,430 lung cancer patients with HIV-unspecified status who underwent resection at Johns Hopkins Hospital from 1985 to 2009. Subcohort comparative analyses were performed using individual matching methods.

Induction therapy for thymic malignancies.

Thymic malignancies are rare tumors of the chest that express a broad range of biological behaviors. Surgery remains the mainstay of therapy, and complete surgical resection is the primary predictor of long-term survival. Although there is a paucity of clinical trials assessing the role of induction/adjuvant chemotherapy and/or radiation therapy in the treatment of thymic malignancies, existing data suggest that induction therapy should be offered for the treatment of advanced-stage disease, and postoperative radiation for specific stages.

Pulmonary resection for isolated pancreatic adenocarcinoma metastasis: an analysis of outcomes and survival.

Objectives: This study was conducted to determine if pulmonary metastasectomy (PM) for isolated pancreatic cancer metastases is safe and effective.

Methods: This was a retrospective case-control study of patients undergoing PM at our institution from 2000 to 2009 for isolated lung metastasis after resection for pancreatic cancer. Clinical and pathologic data were compared with a matched reference group.

Femtosecond laser treatment enhances DNA transfection efficiency in vivo.

Background: Gene therapy with plasmid DNA is emerging as a promising strategy for the treatment of many diseases. One of the major obstacles to such therapy is the poor transfection efficiency of DNA in vivo.

Methods: In this report, we employed a very low power, near-infrared femtosecond laser technique to enhance the transfection efficiency of intradermally and intratumorally administered DNA plasmid.

Prospects of RNA interference therapy for cancer.

RNA interference (RNAi) is a powerful gene-silencing process that holds great promise in the field of cancer therapy. The discovery of RNAi has generated enthusiasm within the scientific community, not only because it has been used to rapidly identify key molecules involved in many disease processes including cancer, but also because RNAi has the potential to be translated into a technology with major therapeutic applications. Our evolving understanding of the molecular pathways important for carcinogenesis has created opportunities for cancer therapy employing RNAi technology to target the key molecules within these pathways.

Rapid upregulation of endothelial P-selectin expression via reactive oxygen species generation.

Endothelial cell ICAM-1 upregulation in response to TNF-alpha is mediated in part by reactive oxygen species (ROS) generated by the endothelial membrane-associated NADPH oxidase and occurs maximally after 4 h as the synthesis of new protein is required. However, thrombin-stimulated P-selectin upregulation is bimodal, the first peak occurring within minutes. We hypothesize that this early peak, which results from the release of preformed P-selectin from within Weibel-Palade bodies, is mediated in part by ROS generated from the endothelial membrane-associated xanthine oxidase.

The physiology of endothelial xanthine oxidase: from urate catabolism to reperfusion injury to inflammatory signal transduction.

Xanthine oxidoreductase (XOR) is a ubiquitous metalloflavoprotein that appears in two interconvertible yet functionally distinct forms: xanthine dehydrogenase (XD), which is constitutively expressed in vivo; and xanthine oxidase (XO), which is generated by the posttranslational modification of XD, either through the reversible, incremental thiol oxidation of sulfhydryl residues on XD or the irreversible proteolytic cleavage of a segment of XD, which occurs at low oxygen tension and in the presence of several proinflammatory mediators. Functionally, both XD and XO catalyze the oxidation of purines to urate. However, whereas XD requires NAD+ as an electron acceptor for these redox reactions, thereby generating the stable product NADH, XO is unable to use NAD+ as an electron acceptor, requiring instead the reduction of molecular oxygen for this purine oxidation and generating the highly reactive superoxide free radical.

Endothelial cells potentiate phagocytic killing by macrophages via platelet-activating factor release.

The immunomodulatory function of endothelial cells (EC) includes the initiation of leukocyte margination, diapedesis, and activation through the upregulation of various cell surface-associated molecules. However, the effect that EC have on the phagocytic function of neighboring monocytes and macrophages is less well described. To address this issue, microvascular EC were cocultured with murine peritoneal macrophages, first in direct contact, then in a noncontact coculture system, and macrophage phagocytosis and phagocytic killing were assessed.

Use of leukocyte depletion to decrease injury after lung preservation and rewarming ischemia: an experimental model.

Background: Hypothermia is critical for proper lung preservation. Ideally, the lungs should be maintained at the optimal preservation temperature during the entire ischemic interval. Lung rewarming during implantation is commonly observed.

L-arginine administration during reperfusion improves pulmonary function.

Background: Nitric oxide is crucial to the maintenance of vascular homeostasis. Because nitric oxide levels decline upon lung reperfusion, infusion of L-arginine, a nitric oxide precursor, during reperfusion might prove effective at ameliorating reperfusion injury.

Methods: Neonatal piglet heart-lung blocks were preserved with Euro-Collins solution for 12 hours, rewarmed at room temperature for 1 hour, and reperfused for 10 minutes with either whole blood (n = 5), whole blood containing L-arginine (10 mmol/L; n = 6), or leukocyte-depleted blood (n = 6) on an isolated, blood-perfused, working heart-lung circuit.

Normocalcemic blood or crystalloid cardioplegia provides better neonatal myocardial protection than does low-calcium cardioplegia.

Although standard blood cardioplegia provides good myocardial protection for cardiac operations in adults, protection of the cyanotic, immature myocardium remains suboptimal. Calcium, which has been implicated in reperfusion injury and in the development of "stone heart" in mature myocardium, is routinely lowered in standard cardioplegic solutions. Immature, neonatal myocardium has lower intracellular calcium stores and is more reliant on extracellular calcium for contraction.

Fluosol cardioplegia results in complete functional recovery: a comparison with blood cardioplegia.

Blood cardioplegia is considered by many to be the preferred solution for myocardial protection. Proposed benefits include the ability to deliver oxygen and the ability to maintain metabolic substrate stores. However, the decreased capacity of blood to release oxygen at hypothermic conditions as well as the presence of deleterious leukocytes, platelets, and complement may limit complete functional recovery.