Radiotherapy and MVA-MUC1-IL-2 vaccine act synergistically for inducing specific immunity to MUC-1 tumor antigen.

Background: We previously demonstrated that tumor irradiation potentiates cancer vaccines using genetic modification of tumor cells in murine tumor models. To investigate whether tumor irradiation augments the immune response to MUC1 tumor antigen, we have tested the efficacy of tumor irradiation combined with an MVA-MUC1-IL2 cancer vaccine (Transgene TG4010) for murine renal adenocarcinoma (Renca) cells transfected with MUC1.

Methods: Established subcutaneous Renca-MUC1 tumors were treated with 8 Gy radiation on day 11 and peritumoral injections of MVA-MUC1-IL2 vector on day 12 and 17, or using a reverse sequence of vaccine followed by radiation.

Soy Isoflavones Promote Radioprotection of Normal Lung Tissue by Inhibition of Radiation-Induced Activation of Macrophages and Neutrophils.

Introduction: Radiation therapy for lung cancer is limited by toxicity to normal lung tissue that results from an inflammatory process, leading to pneumonitis and fibrosis. Soy isoflavones mitigate inflammatory infiltrates and radiation-induced lung injury, but the cellular immune mediators involved in the radioprotective effect are unknown.

Methods: Mice received a single dose of 10 Gy radiation delivered to the lungs and daily oral treatment of soy isoflavones.

Radiation-Induced Esophagitis is Mitigated by Soy Isoflavones.

Introduction: Lung cancer patients receiving radiotherapy present with acute esophagitis and chronic fibrosis, as a result of radiation injury to esophageal tissues. We have shown that soy isoflavones alleviate pneumonitis and fibrosis caused by radiation toxicity to normal lung. The effect of soy isoflavones on esophagitis histopathological changes induced by radiation was investigated.

Axitinib Improves Radiotherapy in Murine Xenograft Lung Tumors.

A third of patients with non-small cell lung cancer (NSCLC) present with un-resectable stage III locally advanced disease and are currently treated by chemo-radiotherapy but the median survival is only about 21months. Using an orthotopic xenograft model of lung carcinoma, we have investigated the combination of radiotherapy with the anti-angiogenic drug axitinib (AG-013736, Pfizer), which is a small molecule receptor tyrosine kinase inhibitor that selectively targets the signal transduction induced by VEGF binding to VEGFR receptors. We have tested the combination of axitinib with radiotherapy in nude mice bearing human NSCLC A549 lung tumors.

Radioprotection of lung tissue by soy isoflavones.

Introduction: Radiation-induced pneumonitis and fibrosis have restricted radiotherapy for lung cancer. In a preclinical lung tumor model, soy isoflavones showed the potential to enhance radiation damage in tumor nodules and simultaneously protect normal lung from radiation injury. We have further dissected the role of soy isoflavones in the radioprotection of lung tissue.

Differential effect of soy isoflavones in enhancing high intensity radiotherapy and protecting lung tissue in a pre-clinical model of lung carcinoma.

Background: Radiotherapy of locally-advanced non-small cell lung cancer is limited by radiation-induced pneumonitis and fibrosis. We have further investigated the role of soy isoflavones to improve the effect of a high intensity radiation and reduce lung damage in a pre-clinical lung tumor model.

Methods: Human A549 NSCLC cells were injected i.

Jump-landing differences between varsity, club, and intramural athletes: the Jump-ACL Study.

Abnormal movement patterns have been identified as important prospective risk factors for lower extremity injury, including anterior cruciate ligament injury. Specifically, poor neuromuscular control during the early landing phase has been associated with increased injury risk. Although it is commonly assumed that higher division collegiate athletes generally exhibit better movement patterns than lower division athletes, few studies compare the biomechanical differences on basic tasks such as jump landing between various levels of athletic groups.

B-DIM impairs radiation-induced survival pathways independently of androgen receptor expression and augments radiation efficacy in prostate cancer.

Increased consumption of cruciferous vegetables is associated with decreased risk in prostate cancer (PCa). The active compound in cruciferous vegetables appears to be the self dimerized product [3,3'-diindolylmethane (DIM)] of indole-3-carbinol (I3C). Nutritional grade B-DIM (absorption-enhanced) has proven safe in a Phase I trial in PCa.

Soy isoflavones radiosensitize lung cancer while mitigating normal tissue injury.

Background: We have demonstrated that soy isoflavones radiosensitize cancer cells. Prostate cancer patients receiving radiotherapy (RT) and soy tablets had reduced radiation toxicity to surrounding organs. We have now investigated the combination of soy with RT in lung cancer (NSCLC), for which RT is limited by radiation-induced pneumonitis.

Monitoring sunitinib-induced vascular effects to optimize radiotherapy combined with soy isoflavones in murine xenograft tumor.

Using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to monitor vascular changes induced by sunitinib within a murine xenograft kidney tumor, we previously determined a dose that caused only partial destruction of blood vessels leading to "normalization" of tumor vasculature and improved blood flow. In the current study, kidney tumors were treated with this dose of sunitinib to modify the tumor microenvironment and enhance the effect of kidney tumor irradiation. The addition of soy isoflavones to this combined antiangiogenic and radiotherapy approach was investigated based on our studies demonstrating that soy isoflavones can potentiate the radiation effect on the tumors and act as antioxidants to protect normal tissues from treatment-induced toxicity.

Soy isoflavones augment radiation effect by inhibiting APE1/Ref-1 DNA repair activity in non-small cell lung cancer.

Introduction: Soy isoflavones sensitize cancer cells to radiation both in vitro and in vivo. To improve the effect of radiotherapy for non-small cell lung cancer, we assessed the potential of using a complementary approach with soy isoflavones.

Methods: Human A549 non-small cell lung cancer cells were treated with soy isoflavones, radiation, or both and tested for cell growth.

Dynamic contrast-enhanced magnetic resonance imaging of sunitinib-induced vascular changes to schedule chemotherapy in renal cell carcinoma xenograft tumors.

In an attempt to develop better therapeutic approaches for metastatic renal cell carcinoma (RCC), the combination of the antiangiogenic drug sunitinib with gemcitabine was studied. Using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), we have previously determined that a sunitinib dosage of 20 mg/kg per day increased kidney tumor perfusion and decreased vascular permeability in a preclinical murine RCC model. This sunitinib dosage causing regularization of tumor vessels was selected to improve delivery of gemcitabine to the tumor.

Daidzein effect on hormone refractory prostate cancer in vitro and in vivo compared to genistein and soy extract: potentiation of radiotherapy.

Purpose: Genistein, the major bioactive isoflavone of soybeans, acts as a radiosensitizer for prostate cancer (PCa) both in vitro and in vivo. However, pure genistein promoted increased metastasis to lymph nodes. A mixture of soy isoflavones (genistein, daidzein, glycitein) did not cause increased metastasis, but potentiated radiotherapy.

Dynamic contrast-enhanced magnetic resonance imaging of vascular changes induced by sunitinib in papillary renal cell carcinoma xenograft tumors.

To investigate further the antiangiogenic potential of sunitinib for renal cell carcinoma (RCC) treatment, its effects on tumor vasculature were monitored by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) using an orthotopic KCI-18 model of human RCC xenografts in nude mice. Tumor-bearing mice were treated with various doses of sunitinib, and vascular changes were assessed by DCE-MRI and histologic studies. Sunitinib induced dose-dependent vascular changes, which were observed both in kidney tumors and in normal kidneys by DCE-MRI.

HSP27 mediates SPARC-induced changes in glioma morphology, migration, and invasion.

Secreted protein acidic and rich in cysteine (SPARC) regulates cell-extracellular matrix interactions that influence cell adhesion and migration. We have demonstrated that SPARC is highly expressed in human gliomas, and it promotes brain tumor invasion in vitro and in vivo. To further our understanding regarding SPARC function in glioma migration, we transfected SPARC-green fluorescent protein (GFP) and control GFP vectors into U87MG cells, and assessed the effects of SPARC on cell morphology, migration, and invasion after 24 h.

SPARC-induced increase in glioma matrix and decrease in vascularity are associated with reduced VEGF expression and secretion.

Glioblastomas are heterogeneous tumors displaying regions of necrosis, proliferation, angiogenesis, apoptosis and invasion. SPARC, a matricellular protein that negatively regulates angiogenesis and cell proliferation, but enhances cell deadhesion from matrix, is upregulated in gliomas (Grades II-IV). We previously demonstrated that SPARC promotes invasion while concomitantly decreasing tumor growth, in part by decreasing proliferation of the tumor cells.

Recognition and management of an orbital blowout fracture in an amateur boxer.

Study Design: Case report.

Objectives: To identify key elements in the recognition and management of a patient with an orbital blowout fracture and make recommendations on diagnosis, treatment, referral, imaging, and return to sports.

Background: Orbital blowout fractures are uncommon but important injuries for physical therapists to recognize.

A standardized protocol for the initial evaluation and documentation of mild brain injury.

Objective: To present a protocol for the initial assessment and documentation of mild brain injury, a protocol that is used within the Department of Physical Education at the United States Military Academy.

Background: Recently, much attention has been given to the assessment and management of mild brain injury by the sports medicine community. Although the classification of and management strategies for mild brain injury have been well disputed, most experts agree on the essentials of the sideline or initial evaluation.

Genetic manipulation of carotenoid biosynthesis in the green sulfur bacterium Chlorobium tepidum.

The green sulfur bacterium Chlorobium tepidum is a strict anaerobe and an obligate photoautotroph. On the basis of sequence similarity with known enzymes or sequence motifs, nine open reading frames encoding putative enzymes of carotenoid biosynthesis were identified in the genome sequence of C. tepidum, and all nine genes were inactivated.

Expression of human intestinal mucin is modulated by the beta-galactoside binding protein galectin-3 in colon cancer.

Background & Aims: Alterations in the production of the beta-galactoside binding protein galectin-3 and of MUC2 intestinal mucin have been independently correlated with the malignant behavior of human colon cancer cells. MUC2 mucin is a major ligand for galectin-3, and colon cancer cells that differ quantitatively in MUC2 expression may also vary in expression of galectin-3. The current study was designed to investigate the relationship between galectin-3 production and MUC2 mucin synthesis by human colon cancer cells.

Collection of free-living nymphs and adults of Amblyomma hebraeum (Acari: Ixodidae) with pheromone/carbon dioxide traps at 5 different ecological sites in heartwater endemic regions of South Africa.

The capture of free-living adults and nymphs of Amblyomma hebraeum, the main vector of heartwater in domestic and wild ruminants in South Africa, by means of attraction-aggregation-attachment-pheromone/carbon dioxide traps at five endemic localities in South Africa is described. Although the traps were used successfully at each of the localities, no determination of their efficiency in relation to the actual abundance of ticks at a particular site was made. This study confirmed that the traps could be used in a variety of ecological areas to locate populations of free-living adult A.

Inhibition of gastric mucin synthesis by Helicobacter pylori.

Background & Aims: Mucins are high-molecular-weight glycoproteins that protect the gastric epithelium. Previous data suggested that gastric surface-type mucin is decreased in Helicobacter pylori-infected patients and restored after eradication of the infection. Our aim was to determine the effect of H.

Liver colonization by human colon cancer cells is reduced by antisense inhibition of MUC2 mucin synthesis.

Background & Aims: Alterations in the production of epithelial mucins have been correlated with advanced tumor stage in the colon, but direct evidence for a role of specific mucin genes in liver metastasis is lacking. The current study was designed to establish more directly the role of MUC2 in colon cancer metastasis.

Methods: MUC2 levels were manipulated in highly metastatic human colon cancer cells using eukaryotic expression constructs designed to express a portion of MUC2 complementary DNA in antisense orientation.

Metastasis of human colon cancer is altered by modifying expression of the beta-galactoside-binding protein galectin 3.

Background & Aims: Galectin 3 is a beta-galactoside-binding protein whose expression has been correlated with advanced tumor stage in the colon, but direct evidence for a role in metastasis is lacking. The current study was designed to more directly establish the role of galectin 3 in colon cancer metastasis.

Methods: Galectin 3 levels were manipulated in human colon cancer cells using eukaryotic expression constructs designed to express the complete galectin 3 complementary DNA in either the sense or antisense orientation.