Knowledge translation: Radiographers compared to other healthcare professionals.

OBJECTIVES: This narrative review examines the current status of evidence-based practice and knowledge translation in diagnostic radiography. It explores knowledge translation efforts in the allied health professions aimed at systematically implementing evidence-based practice and suggests ways that these may be applied within diagnostic radiography. KEY FINDINGS: Knowledge translation in diagnostic radiography is in its infancy with numerous examples of key findings of rigorous studies not implemented in practice. Utilising frameworks, models and theories to systematically translate knowledge into evidence-based practice has been shown to be effective in other allied health professions. Whilst few studies in diagnostic radiography report utilising these systematic approaches to implementing evidence-based practice, those that do, show promising results. Attitudes towards evidence-based practice within diagnostic radiography are becoming more positive and it is important to use this positive shift in attitudes to create real evidence-based change in the profession. CONCLUSION: The potential benefits of systematically translating knowledge into evidence-based practice in diagnostic radiography are wide reaching with positive implications for our patients, the profession and wider community. Leaders at all levels of radiography must work towards implementing evidence-based practice in their daily work. IMPLICATIONS FOR PRACTICE: Systematic approaches to knowledge translation should be adopted and reported in diagnostic radiography in order to more effectively translate knowledge into evidence-based practice.

Investigation of Chiral Recognition by Molecular Micelles with Molecular Dynamics Simulations.

Molecular dynamics simulations were used to characterize the binding of the chiral drugs chlorthalidone and lorazepam to the molecular micelle poly-(sodium undecyl-(L)-leucine-valine). The project's goal was to characterize the nature of chiral recognition in capillary electrophoresis separations that use molecular micelles as the chiral selector. The shapes and charge distributions of the chiral molecules investigated, their orientations within the molecular micelle chiral binding pockets, and the formation of stereoselective intermolecular hydrogen bonds with the molecular micelle were all found to play key roles in determining where and how lorazepam and chlorthalidone enantiomers interacted with the molecular micelle.

Molecular Dynamics Simulation and NMR Investigation of the Association of the ß-Blockers Atenolol and Propranolol with a Chiral Molecular Micelle.

Molecular dynamics simulations and NMR spectroscopy were used to compare the binding of two ß-blocker drugs to the chiral molecular micelle poly-(sodium undecyl-(L)-leucine-valine). The molecular micelle is used as a chiral selector in capillary electrophoresis. This study is part of a larger effort to understand the mechanism of chiral recognition in capillary electrophoresis by characterizing the molecular micelle binding of chiral compounds with different geometries and charges. Propranolol and atenolol were chosen because their structures are similar, but their chiral interactions with the molecular micelle are different. Molecular dynamics simulations showed both propranolol enantiomers inserted their aromatic rings into the molecular micelle core and that (S)-propranolol associated more strongly with the molecular micelle than (R)-propranolol. This difference was attributed to stronger molecular micelle hydrogen bonding interactions experienced by (S)-propranolol. Atenolol enantiomers were found to bind near the molecular micelle surface and to have similar molecular micelle binding free energies.

Symptom Burden and Functional Gains in a Cancer Rehabilitation Unit.

BACKGROUND/AIMS: To determine if there is a relationship between patient symptoms and functional improvement on inpatient rehabilitation. METHODS: Retrospective review of medical records at an American tertiary referral-based cancer center of all patients admitted to an inpatient rehabilitation unit between 3/1/2013-5/20/2013. Main outcome measures included the Edmonton Symptom and Assessment Scale (ESAS) and Functional Independence Measure (FIM). FINDINGS: The medical records for 71 unique cancer rehabilitation inpatients were analyzed. Statistical analysis of total admission ESAS on total FIM change found no significant relationships. The symptom burden of the patients was mild. Patients demonstrated statistically significant improvements in function and symptoms during inpatient rehabilitation. The mean change in total FIM and total ESAS were an increase of 19.20 and decrease of 7.41 respectively. Statistically significant changes occurred in fatigue, sleep, pain, and anxiety. CONCLUSION: Both symptom and functional scores improved significantly during inpatient rehabilitation. However, no significant relationships were found between symptoms at admission and improvement in FIM.

Self-cross-linked hyaluronic acid hydrogel in ethmoidectomy: a randomized, controlled trial.

BACKGROUND: This study was designed to evaluate the safety and efficacy of a novel, self-cross-linked hyaluronic acid (HA) hydrogel compared with carboxymethylcellulose (CMC) viscous foam in promoting healing when applied after ethmoidectomy. A prospective, randomized, controlled, blinded clinical trial was performed. The study was performed by four surgeons operating in two community hospitals. METHODS: Thirty patients with bilateral chronic rhinosinusitis underwent bilateral total ethmoidectomy. Intraoperatively, each patient received 5 mL of HA hydrogel in one ethmoid cavity and 5 mL of CMC contralaterally. The material applied within each ethmoid cavity was randomly assigned before surgery. An independent surgeon, blinded to the material used to treat each ethmoid cavity, evaluated postoperative endoscopic video at 1 and 2 weeks for edema, crusting, and mucopurulence and at 6 and 12 weeks for remucosalization and scarring/synechiae. Twenty-item Sino-Nasal Outcome Test SNOT-20 data were collected at each visit. A small sample underwent endoscopic mucosal biopsy. RESULTS: Twenty-nine of 30 patients completed the protocol. The difference in edema, crusting, and mucopurulence at 1 and 2 weeks was not statistically significant; however, at 6 and 12 weeks, the HA hydrogel showed statistically significant reduction in both overall endoscopic grade (p < 0.05), as well as synechiae formation (p < 0.05), with a trend toward superiority in remucosalization (p = 0.08). Histological analysis of six subjects at 12 weeks showed a nonsignificant trend toward a greater amount of regenerated cilia present with the HA hydrogel (p = 0.23). SNOT-20 scores declined 78.8% from preoperative scores. CONCLUSION: Self-cross-linked HA hydrogel provides superior wound healing to CMC after ethmoidectomy.

Safety, feasibility, and efficacy of placement of steroid-eluting bioabsorbable sinus implants in the office setting: a prospective case series.

BACKGROUND: The outcomes of endoscopic sinus surgery (ESS) for chronic rhinosinusitis (CRS) can be compromised by postoperative inflammation, recurrent polyposis, middle turbinate lateralization, and synechiae, often requiring subsequent interventions. A bioabsorbable steroid-eluting sinus implant placed in the operating room following ESS has been proven safe and effective in 2 randomized controlled trials and a subsequent meta-analysis, for its ability to preserve sinus patency, and reduce medical and surgical interventions. This trial sought to evaluate the safety, feasibility, and outcomes of implants placed in the office after achieving hemostasis. METHODS: Twenty patients with CRS underwent ESS including bilateral ethmoidectomy. A steroid-eluting bioabsorbable implant was deployed into each ethmoid cavity in the office within 7 days after ESS. Endoscopic appearance of the ethmoid cavities was evaluated at 1 week, 2 weeks, and 4 weeks postoperatively by the operating surgeon and an independent blinded evaluator. Procedural tolerance was assessed at week 2 using a patient preference questionnaire. The 20-item Sino-Nasal Outcome Test (SNOT-20) questionnaire was completed at baseline, week 2, and week 4. RESULTS: In-office placement of steroid-eluting bioabsorbable implants was well tolerated, with 90% of patients very satisfied with the overall experience, and 80% very satisfied with the recovery process. At 1 month, there were no significant adhesions or frank polyposis, and middle turbinate lateralization was only 5%. Compared to baseline, ethmoid sinus inflammation was significantly reduced (p = 0.03), and the mean SNOT-20 score was significantly improved (p < 0.001). CONCLUSION: In-office placement of steroid-eluting bioabsorbable implants after achieving hemostasis was well tolerated and might improve local drug diffusion and surgical outcomes.

A Molecular Dynamics Simulation Study of the Association of 1,1'-Binaphthyl-2,2'-diyl hydrogenphosphate Enantiomers with a Chiral Molecular Micelle.

Molecular dynamics (MD) simulations were used to investigate the binding of 1,1'-binaphthyl-2,2'-diyl hydrogenphosphate (BNP) enantiomers to the molecular micelle poly-(sodium undecyl-(L,L)-leucine-valine) (poly(SULV)). Poly(SULV) is used as a chiral selector in capillary electrophoresis separations. Four poly(SULV) binding pockets were identified and either (R)-BNP or (S)-BNP were docked into each pocket. MD simulations were then used to identify the preferred BNP binding site. Within the preferred site, both enantiomers formed hydrogen bonds with poly(SULV) and penetrated into the poly(SULV) core. Comparisons of BNP enantiomer binding to the preferred poly(SULV) pocket showed that (S)-BNP formed stronger hydrogen bonds, moved deeper into the binding site, and had a lower poly(SULV) binding free energy than the (R) enantiomer. Finally, MD simulation results were in agreement with capillary electrophoresis and NMR experiments. Each technique showed (S)-BNP interacted more strongly with poly(SULV) than (R)-BNP and that the site of chiral recognition was near the poly(SULV) leucine chiral center.

A Molecular Dynamics Simulation Study of Two Dipeptide Based Molecular Micelles: Effect of Amino Acid Order.

Molecular dynamics (MD) simulations were used to compare the structures of the chiral molecular micelles (MM) poly-(sodium undecyl-(L,L)-leucine-valine) (poly(SULV)) and poly-(sodium undecyl-(L,L)-valine-leucine) (poly (SUVL)). Both MM contained polymerized surfactant monomers tenninated by chiral dipeptide headgroups. The study was undertaken to investigate why poly(SULV) is generally a better chiral selector compared to poly(SUVL) in electrokinetic chromatography separations. When comparing poly(SULV) to poly(SUVL), poly(SULV) had the more conformational flexible dipeptide headgroup and hydrogen bond analyses revealed that the poly(SULV) headgroup conformation allowed a larger number of intramolecular hydrogen bonds to form between monomer chains. In addition, a larger number of water molecules surrounded the chiral centers of the poly(SULV) molecular micelle. Poly(SULV) was also found to have a larger solvent accessible surface area (SASA) than poly(SUVL) and fluctuations in the poly(SULV) SASA during the MD simulation allowed dynamic monomer chain motions expected to be important in chiral recognition to be identified. Finally, approximately 50% of the Na+ counterions were found in the first three solvation shells surrounding both MM, with the remainder located in the bulk. Overall the MD simulations point to both greater headgroup flexibility and solvent and analyte access to the chiral centers of the dipeptide headgroup as factors contributing to the enhanced chiral selectivity observed with poly(SULV).

Granulocyte transfusions in fulminant invasive fungal sinusitis.

PURPOSE: Fulminant invasive fungal sinusitis (IFS) is an aggressive disease seen in patients who are severely neutropenic. The use of granulocyte transfusions to address neutropenia-associated IFS has been described for almost 2 decades. The objectives are to provide our experience using granulocyte transfusions in patients with IFS and to provide a current review of the literature. MATERIALS AND METHODS: A retrospective chart review was performed at the Medical College of Wisconsin to identify patients who received granulocyte transfusions for IFS. Data collected included age, original diagnosis, IFS pathogen, dates, transfusion number, reason for discontinuation, additional therapies, last known follow-up, and status at last known follow-up. A Medline search and manual review of citations within bibliographies was also performed. RESULTS: A total of 20 patients received granulocyte transfusions at the Medical College of Wisconsin between October 2003 and June 2009; 3 of these patients received granulocyte transfusions for fulminant IFS. A total of 22 reported cases of IFS treated with granulocyte transfusions exist in the current literature. CONCLUSIONS: Although limitations to the use of granulocyte transfusions exist, they still represent a viable treatment option in individuals who fail to respond to more conventional therapies.

Investigation of Chiral Molecular Micelles by NMR Spectroscopy and Molecular Dynamics Simulation.

NMR spectroscopy and molecular dynamics (MD) simulation analyses of the chiral molecular micelles poly-(sodium undecyl-(L,L)-leucine-valine) (poly-SULV) and poly-(sodium undecyl-(L,L)- valine-leucine) (poly-(SUVL)) are reported. Both molecular micelles are used as chiral selectors in electrokinetic chromatography and each consists of covalently linked surfactant chains with chiral dipeptide headgroups. To provide experimental support for the structures from MD simulations, NOESY spectra were used to identify protons in close spatial proximity. Results from the NOESY analyses were then compared to radial distribution functions from MD simulations. In addition, the hydrodynamic radii of both molecular micelles were calculated from NMR-derived diffusion coefficients. Corresponding radii from the MD simulations were found to be in agreement with these experimental results. NMR diffusion experiments were also used to measure association constants for polar and non-polar binaphthyl analytes binding to both molecular micelles. Poly(SUVL) was found to bind the non-polar analyte enantiomers more strongly, while the more polar analyte enantiomers interacted more strongly with poly(SULV). MD simulations in tum showed that poly(SUL V) had a more open structure that gave greater access for water molecules to the dipeptide headgroup region.

Sinus preservation management for frontal sinus fractures in the endoscopic sinus surgery era: a systematic review.

We systematically reviewed the existing literature supporting the efficacy and safety of sinus preservation management for frontal sinus fractures in the modern era of endoscopic frontal sinus surgery. A systematic review of the English literature for the targeted objective was conducted using the PubMed database between January 1995 and August 2008. The PubMed database was queried using two major search terms of frontal sinus fracture or frontal sinus injury along with manual review of citations within bibliographies. Citations acquired from the primary search were filtered and relevant abstracts were identified that merited full review. Articles were identified that included any cohort of patients with frontal sinus fractures involving the frontal sinus outflow tract or posterior wall with sinus preservation management. A total of 231 citations were generated, and 56 abstracts were identified as potentially relevant articles. Sixteen articles merited full review, with seven articles meeting inclusion criteria for sinus preservation. There were 515 total patients in the studies with 350 patients managed with frontal sinus preservation. Similar short-term complications and effectiveness were found between fractures managed with sinus preservation and those with traditional management. Sinus preservation appears to be a safe and effective management strategy for select frontal sinus fractures. More transparent reporting of management strategies for individual cases or cohorts is needed. A standardized algorithm and categorization framework for future studies are proposed. Longer-term follow-up and larger prospective studies are necessary to assess the safety and efficacy of sinus preservation protocols.

Right atrial isomerism: preponderance in Asian fetuses. Using the stomach-distance ratio as a possible diagnostic tool for prediction of right atrial isomerism.

INTRODUCTION: To present the characteristics and spectrum of associated anomalies in right- and left-sided isomerism in our local population and to assess the possibility of using stomach-distance ratio (SDR) of less than 0.34 as a diagnostic tool to predict right atrial isomerism. MATERIALS AND METHODS: This was a retrospective study of fetuses in our department over a period of 8 years with postnatally confirmed prenatal diagnosis of atrial isomerism. RESULTS: In 22 cases, atrial isomerism was confirmed by post-mortem or postnatal echocardiography. Eighteen (81.8%) fetuses had right isomerism. Their main abnormal ultrasound findings were pulmonary stenosis or atresia (n = 9), atrioventricular septal defect (n = 10), right-sided stomach (n = 9), transposition of great arteries (n = 6), dextrocardia (n = 8), single ventricle (n = 4), juxtaposition of inferior vena cava and descending aorta (n = 5), ventricular septal defect (n = 2), interrupted inferior vena cava with azygous drainage (n = 2) and double outlet right ventricle (n = 3). Four (18.2%) fetuses had left isomerism. Their abnormal ultrasound findings were dextrocardia (n = 3), right-sided stomach (n = 3), atrioventricular septal defect (n = 2), double outlet ventricle (n = 2), ventricular septal defect (n = 1), pulmonary stenosis (n = 2) and interrupted inferior vena cava with azygous drainage (n = 1). 66.7% (12/18) of cases with right isomerism had SDR of less than 0.34 compared to 0% (0/4) of the cases with left isomerism (P = 0.02). CONCLUSION: Our study suggests an Asian predilection towards right isomerism compared to Western populations. We postulate that there may be racial differences in the expression of these 2 forms of isomerism. The ultrasound findings of complex heart disease and abnormal arrangement of great vessels in abdominal cavity, though important, are varied and non-specific evidence for either form of fetal atrial isomerism. There is a possibility of using the SDR <0.34 (representing stomach proximity to the fetal spine) as a possible diagnostic tool to predict right-sided atrial isomerism.

Improved oxygen diffusion and mechanical aggregation of tumor colonies in a novel stirred mini-bioreactor.

The feasibility of a novel stirred bioreactor, the rotating aerial disk (RAD) design, was tested in this study. The novelty lies in its method of medium recirculation by convective airflow using a non-contact planar disc, a variation on a physically defined theoretical model. Computational predictions of improved oxygenation were confirmed by increases in measured dissolved oxygen, even at Reynolds numbers (100-200) where flow is mostly laminar. EL-4 mouse lymphoma cells grown for the first time as suspension cultures in the RAD bioreactor, were mechanically re-organization into dense, circular three-dimensional colonies (diameter 3-5 mm, thickness 5-800 microm), more rapidly than we have observed previously. Cell proliferation in the RAD vessels was similar to static cultures, although lactate production from glucose was significantly lower, suggesting a shift toward aerobic glycolysis. This possible reversal of the 'Warburg effect' was accompanied by a decrease in mitochondrial activity, perhaps reflecting a more quiescent cytoplasmic state. The RAD device may be useful as scalable, three-dimensional solid tumor model under more physiological conditions then static culture.

Right atrial isomerism: preponderance in Asian fetuses. Using the stomach-distance ratio as a possible diagnostic tool for prediction of right atrial isomerism

<p><b>INTRODUCTION</b>To present the characteristics and spectrum of associated anomalies in right- and left-sided isomerism in our local population and to assess the possibility of using stomach-distance ratio (SDR) of less than 0.34 as a diagnostic tool to predict right atrial isomerism.</p><p><b>MATERIALS AND METHODS</b>This was a retrospective study of fetuses in our department over a period of 8 years with postnatally confirmed prenatal diagnosis of atrial isomerism.</p><p><b>RESULTS</b>In 22 cases, atrial isomerism was confirmed by post-mortem or postnatal echocardiography. Eighteen (81.8%) fetuses had right isomerism. Their main abnormal ultrasound findings were pulmonary stenosis or atresia (n = 9), atrioventricular septal defect (n = 10), right-sided stomach (n = 9), transposition of great arteries (n = 6), dextrocardia (n = 8), single ventricle (n = 4), juxtaposition of inferior vena cava and descending aorta (n = 5), ventricular septal defect (n = 2), interrupted inferior vena cava with azygous drainage (n = 2) and double outlet right ventricle (n = 3). Four (18.2%) fetuses had left isomerism. Their abnormal ultrasound findings were dextrocardia (n = 3), right-sided stomach (n = 3), atrioventricular septal defect (n = 2), double outlet ventricle (n = 2), ventricular septal defect (n = 1), pulmonary stenosis (n = 2) and interrupted inferior vena cava with azygous drainage (n = 1). 66.7% (12/18) of cases with right isomerism had SDR of less than 0.34 compared to 0% (0/4) of the cases with left isomerism (P = 0.02).</p><p><b>CONCLUSION</b>Our study suggests an Asian predilection towards right isomerism compared to Western populations. We postulate that there may be racial differences in the expression of these 2 forms of isomerism. The ultrasound findings of complex heart disease and abnormal arrangement of great vessels in abdominal cavity, though important, are varied and non-specific evidence for either form of fetal atrial isomerism. There is a possibility of using the SDR <0.34 (representing stomach proximity to the fetal spine) as a possible diagnostic tool to predict right-sided atrial isomerism.</p>

Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) composite biomaterials for bone tissue regeneration: in vitro performance assessed by osteoblast proliferation, osteoclast adhesion and resorption, and macrophage proinflammatory response.

The efficacy of composite materials for bone tissue engineering is dependent on the materials' ability to support bone regeneration whilst inducing a minimal inflammatory response. In this study we examined the in vitro osteogenic and inflammatory properties of poly(3-hydroxybutyrate-co-3-valerate) (PHBV) with various calcium phosphate-reinforcing phases: nano-sized hydroxyapatite (HA); submicron-sized calcined hydroxyapatite (cHA); and submicron-sized beta-tricalcium phosphate (beta-TCP), using bioassays of cultured osteoblasts, osteoclasts, and macrophages. Our study showed that the addition of a nano-sized reinforcing phase to PHBV, whilst improving osteogenic properties, also reduces the proinflammatory response. Proinflammatory responses of RAW264.7/ELAM-eGFP macrophages to PHBV were shown to be markedly reduced by the introduction of a reinforcing phase, with HA/PHBV composites having the lowest inflammatory response. Osteoclasts, whilst able to attach to all the materials, failed to form functional actin rings or resorption pits on any of the materials under investigation. Cultures of osteoblasts (MC3T3-E1) readily attached and mineralised on all the materials, with HA/PHBV inducing the highest levels of mineralization. The improved biological performance of HA/PHBV composites when compared with cHA/PHBV and beta-TCP/PHBV composites is most likely a result of the nano-sized reinforcing phase of HA/PHBV and the greater surface presentation of mineral in these composites. Our results provide a new strategy for improving the suitability of PHBV-based materials for bone tissue regeneration.

Diastereoselective DNA cleavage recognition by Ni(II) x Gly-Gly-His-derived metallopeptides.

Site-selective DNA cleavage by diastereoisomers of Ni(II) x Gly-Gly-His-derived metallopeptides was investigated through high-resolution gel analyses and molecular dynamics simulations. Ni(II) x L-Arg-Gly-His and Ni(II) x D-Arg-Gly-His (and their respective Lys analogues) targeted A/T-rich regions; however, the L-isomers consistently modified a subset of available nucleotides within a given minor groove site, while the D-isomers differed in both their sites of preference and their ability to target individual nucleotides within some sites. In comparison, Ni(II) x L-Pro-Gly-His and Ni(II) x D-Pro-Gly-His were unable to exhibit a similar diastereoselectivity. Simulations of the above systems, along with Ni(II) x Gly-Gly-His, indicated that the stereochemistry of the amino-terminal amino acid produces either an isohelical metallopeptide that associates stably at individual DNA sites (L-Arg or L-Lys) or, with D-Arg and D-Lys, a noncomplementary metallopeptide structure that cannot fully employ its side chain nor amino-terminal amine as positional stabilizing moieties. In contrast, amino-terminal Pro-containing metallopeptides of either stereochemistry, lacking an extended side chain directed toward the minor groove, did not exhibit a similar diastereoselectivity. While the identity and stereochemistry of amino acids located in the amino-terminal peptide position influenced DNA cleavage, metallopeptide diastereoisomers containing L- and D-Arg (or Lys) within the second peptide position did not exhibit diastereoselective DNA cleavage patterns; simulations indicated that a positively charged amino acid in this location alters the interaction of the metallopeptide equatorial plane and the minor groove leading to an interaction similar to Ni(II) x Gly-Gly-His.

Molecular Dynamics Simulations of the Orientation of Ni(II)•Gly-Gly-His and Ni(II)•Arg-Gly-His Metallopeptide-DNA Association.

Ni(II)•Xaa-Gly-His metallopeptides (where Xaa is any α-amino acid) bind selectively to the minor groove of A/T-rich DNA regions as a function of their amino acid composition and chirality. Molecular dynamics simulations were performed to clarify the most likely binding orientations of Ni(II)•Gly-Gly-His and Ni(II)•L-Arg-Gly-His upon association with the B-form oligonucleotide d(CGCGAATTCGCG)2. Upon examination of four possible docking orientations (I-IV), these studies indicated that both metallopeptides favor association with DNA via I, involving insertion of the edge of the metallopeptide containing the amino-terminal N-H and the imidazole pyrrole N-H group of His into the minor groove. These metallopeptide moieties play important roles in this DNA recognition mode by functioning as H-bond donors to minor groove acceptors such as the N3 of adenine or the O2 of thymine located on the floor of the minor groove. The positively charged side chain of L-Arg was found to enhance DNA recognition relative to that exhibited by Ni(II)•Gly-Gly-His through an increased electrostatic interaction, its favorable stereochemistry, and by providing a third point of contact with the minor groove floor. The simulation of orientation I was found to reproduce the experimentally supported DNA-metallopeptide orientation, revealing factors that are important for the further development of DNA-binding ligands.

Antivascular therapy of oral tongue squamous cell carcinoma with PTK787.

OBJECTIVES/HYPOTHESIS: Vascular endothelial growth factor (VEGF) is an important mediator in tumor vascularization, growth, and metastasis. We investigated whether blockade of the VEGF receptor (VEGF-R) signaling pathway by the tyrosine kinase inhibitor PTK787 combined with CPT-11, a semisynthetic camptothecin analogue, can inhibit the tumor growth and angiogenesis of squamous cell carcinoma of the oral tongue in an orthotopic nude mouse model. METHODS: JMAR human oral squamous cell carcinoma cells were injected into the tongues of nude mice. Seven days later, the mice were randomized to receive a placebo, daily oral PTK787, weekly CPT-11 injection, or PTK787 plus CPT-11. After 4 weeks of treatment, the mice underwent necropsy, and the tongue tumors, cervical lymph nodes, and lungs were removed for immunohistochemical analyses. RESULTS: CPT-11, PTK787, and PTK787 plus CPT-11 significantly decreased tumor volumes and prolonged survival. The combination treatment group had the most significant decrease in volume and increase in survival. PTK787 alone or in combination with CPT-11 reduced the phosphorylation of VEGF-R in tumor cells and tumor-associated endothelial cells, was associated with decreased microvessel density, a decreased proliferative index, and an increased apoptotic index. PTK787 alone or the combination therapy resulted in apoptosis of both tumor cells and tumor-associated endothelial cells. CONCLUSIONS: These results suggest that targeting VEGF-R tyrosine kinase activity can be an effective therapeutic approach in squamous cell carcinoma of the oral tongue.