A novel technique for quantifying changes in vascular density, endothelial cell proliferation and protein expression in response to modulators of angiogenesis using the chick chorioallantoic membrane (CAM) assay

Reliable quantitative evaluation of molecular pathways is critical for both drug discovery and treatment monitoring. We have modified the CAM assay to quantitatively measure vascular density, endothelial proliferation, and changes in protein expression in response to anti-angiogenic and pro-angiogenic agents. This improved CAM assay can correlate changes in vascular density with changes seen on a molecular level. We expect that these described modifications will result in a single in vivo assay system, which will improve the ability to investigate molecular mechanisms underlying the angiogenic response

Gene expression profiling of alveolar soft-part sarcoma (ASPS)

<p>Abstract</p> <p>Background</p> <p>Alveolar soft-part sarcoma (ASPS) is an extremely rare, highly vascular soft tissue sarcoma affecting predominantly adolescents and young adults. In an attempt to gain insight into the pathobiology of this enigmatic tumor, we performed the first genome-wide gene expression profiling study.</p> <p>Methods</p> <p>For seven patients with confirmed primary or metastatic ASPS, RNA samples were isolated immediately following surgery, reverse transcribed to cDNA and each sample hybridized to duplicate high-density human U133 plus 2.0 microarrays. Array data was then analyzed relative to arrays hybridized to universal RNA to generate an unbiased transcriptome. Subsequent gene ontology analysis was used to identify transcripts with therapeutic or diagnostic potential. A subset of the most interesting genes was then validated using quantitative RT-PCR and immunohistochemistry.</p> <p>Results</p> <p>Analysis of patient array data versus universal RNA identified elevated expression of transcripts related to angiogenesis (ANGPTL2, HIF-1 alpha, MDK, c-MET, VEGF, TIMP-2), cell proliferation (PRL, IGFBP1, NTSR2, PCSK1), metastasis (ADAM9, ECM1, POSTN) and steroid biosynthesis (CYP17A1 and STS). A number of muscle-restricted transcripts (ITGB1BP3/MIBP, MYF5, MYF6 and TRIM63) were also identified, strengthening the case for a muscle cell progenitor as the origin of disease. Transcript differentials were validated using real-time PCR and subsequent immunohistochemical analysis confirmed protein expression for several of the most interesting changes (MDK, c-MET, VEGF, POSTN, CYP17A1, ITGB1BP3/MIBP and TRIM63).</p> <p>Conclusion</p> <p>Results from this first comprehensive study of ASPS gene expression identifies several targets involved in angiogenesis, metastasis and myogenic differentiation. These efforts represent the first step towards defining the cellular origin, pathogenesis and effective treatment strategies for this atypical malignancy.</p

Compositions and methods for reducing or preventing medical device-related infections

Provided herein is a method of reducing a microbial infection of a heparinized surface wherein heparin precipitation is reduced as compared to a control. In some embodiments a composition comprising ethanol and isopropanol is applied to the surface. In other embodiments, two or more ethanol compositions are applied and removed sequentially from the surface prior to contacting the surface with a biological fluid, tissue or vessel, wherein the composition in each successive administration comprises an increased amount of ethanol. Also provided is a method of reducing a microbial infection of a surface comprising applying a mucilage extract from an Opuntia ficus indica species to the surface

Compositions and methods for reducing or preventing medical device-related infections

Provided herein is a method of reducing a microbial infection of a heparinized surface wherein heparin precipitation is reduced as compared to a control. In some embodiments a composition comprising ethanol and isopropanol is applied to the surface. In other embodiments, two or more ethanol compositions are applied and removed sequentially from the surface prior to contacting the surface with a biological fluid, tissue or vessel, wherein the composition in each successive administration comprises an increased amount of ethanol. Also provided is a method of reducing a microbial infection of a surface comprising applying a mucilage extract from an Opuntia ficus indica species to the surface

Ureteral reconstruction for retroperitoneal tumors in children.

PURPOSE: Removal of solid tumors of the pelvis and abdominal cavity may require resection of an involved ureteral segment. Ureteral stricture can also be a result of intense therapy. We present our experience with urinary reconstruction in this situation. METHODS: A retrospective review of pediatric oncology patients with solid abdominal/pelvic tumors who underwent a ureteral reconstructive procedure was done. Institutional review board wavier was obtained for the review. Patient data were collected on diagnosis, procedures performed, renal function, and follow-up. RESULTS: Thirteen patients were identified: 8 male and 5 female. The mean age at surgery was 10.1 years. The most common reason for surgery was en bloc tumor resection (n = 8) followed by ureteral strictures (n = 3). The Boari flap, Leadbetter-Politano reimplantation, and psoas hitch were the most common procedures preformed. Follow-up studies included measurements of serum urea nitrogen/creatinine levels as well as renal scans to assess functional status; 2 patients had elevated serum urea nitrogen/creatinine levels at follow-up. The mean follow-up time was 18 months; 4 patients died-none was secondary to renal complications. There were no local tumor recurrences. CONCLUSIONS: Abdominal and pelvic tumors frequently involve the ureter, and their removal should not necessitate acceptance of poor surgical margins. Complete surgical resection of tumor including involved ureteral segments can prolong survival in patients with extensive abdominopelvic cancers. In another group of patients, ureteral strictures arise secondary to therapy and reconstruction may preserve renal function

Health Inequities in Pediatric Trauma

This review article highlights the disparities evident in pediatric trauma care in the United States. Social determinants of health play a significant role in key aspects of trauma care including access to care, gun violence, child abuse, head trauma, burn injuries, and orthopedic trauma. We review the recent literature as it relates to these topics. The findings from these recent studies emphasize the important principle that trauma care for children should be designed with a focus on equity for all children

Outcomes After Preoperative Chemoradiation With or Without Pazopanib in Non-Rhabdomyosarcoma Soft Tissue Sarcoma: A Report From Children\u27s Oncology Group and NRG Oncology

JCO ARST1321 was a phase II study designed to compare the near complete pathologic response rate after preoperative chemoradiation with/without pazopanib in children and adults with intermediate-/high-risk chemotherapy-sensitive body wall/extremity non-Rhabdomyosarcoma Soft Tissue Sarcoma (ClinicalTrials.gov identifier: NCT02180867). Enrollment was stopped early following a predetermined interim analysis that found the rate of near complete pathologic response to be significantly greater with the addition of pazopanib. As a planned secondary aim of the study, the outcome data for this cohort were analyzed. Eight-five eligible patients were randomly assigned to receive (regimen A) or not receive (regimen B) pazopanib in combination with ifosfamide and doxorubicin + preoperative radiotherapy followed by primary resection at week 13 and then further chemotherapy at week 25. As of December 31, 2021, at a median survivor follow-up of 3.3 years (range, 0.1-5.8 years), the 3-year event-free survival for all patients in the intent-to-treat analysis was 52.5% (95% CI, 34.8 to 70.2) for regimen A and 50.6% (95% CI, 32 to 69.2) for regimen B ( = .8677, log-rank test); the 3-year overall survival was 75.7% (95% CI, 59.7 to 91.7) for regimen A and 65.4% (95% CI, 48.1 to 82.7) for regimen B ( = .1919, log-rank test). Although the rate of near complete pathologic response was significantly greater with the addition of pazopanib, outcomes were not statistically significantly different between the two regimens