Gerardo Valadez J.,Vanderbilt Medical Center |
Grover V.K.,Vanderbilt Medical Center |
Carter M.D.,Vanderbilt Medical Center |
Calcutt M.W.,Vanderbilt Medical Center |
And 6 more authors.
Cancer Letters | Year: 2013
The Hedgehog (Hh) pathway regulates the growth of a subset of adult gliomas and better definition of Hh-responsive subtypes could enhance the clinical utility of monitoring and targeting this pathway in patients. Somatic mutations of the isocitrate dehydrogenase (IDH) genes occur frequently in WHO grades II and III gliomas and WHO grade IV secondary glioblastomas. Hh pathway activation in WHO grades II and III gliomas suggests that it might also be operational in glioblastomas that developed from lower-grade lesions. To evaluate this possibility and to better define the molecular and histopathological glioma subtypes that are Hh-responsive, IDH genes were sequenced in adult glioma specimens assayed for an operant Hh pathway. The proportions of grades II-IV specimens with IDH mutations correlated with the proportions that expressed elevated levels of the Hh gene target PTCH1. Indices of an operational Hh pathway were measured in all primary cultures and xenografts derived from IDH-mutant glioma specimens, including IDH-mutant glioblastomas. In contrast, the Hh pathway was not operational in glioblastomas that lacked IDH mutation or history of antecedent lower-grade disease. IDH mutation is not required for an operant pathway however, as significant Hh pathway modulation was also measured in grade III gliomas with wild-type IDH sequences. These results indicate that the Hh pathway is operational in grades II and III gliomas and glioblastomas with molecular or histopathological evidence for evolvement from lower-grade gliomas. Lastly, these findings suggest that gliomas sharing this molecularly defined route of progression arise in Hh-responsive cell types. © 2012.
Rush S.Z.,Vanderbilt Medical Center |
Rush S.Z.,University of Colorado at Denver |
Abel T.W.,Vanderbilt Medical Center |
Valadez J.G.,Vanderbilt Medical Center |
And 3 more authors.
Neuro-Oncology | Year: 2010
Pilocytic astrocytoma is commonly viewed as a benign lesion. However, disease onset is most prevalent in the first two decades of life, and children are often left with residual or recurrent disease and significant morbidity. The Hedgehog (Hh) pathway regulates the growth of higher WHO grade gliomas, and in this study, we have evaluated the activation and operational status of this regulatory pathway in pilocytic astrocytomas. Expression levels of the Hh pathway transcriptional target PTCH were elevated in 45% of tumor specimens analyzed (ages 1-22 years) and correlated inversely with patient age. Evaluation of a tissue array revealed oligodendroglioma-like features, pilomyxoid features, infiltration, and necrosis more commonly in specimens from younger patients (below the median patient age of 10 years). Immunohistochemical staining for the Hh pathway components PTCH and GLI1 and the proliferation marker Ki67 demonstrated that patients diagnosed before the age of 10 had higher staining indices than those diagnosed after the age of 10. A significant correlation between Ki67 and PTCH and GLI1 staining indices was measured, and 86% of Ki67-positive cells also expressed PTCH. The operational status of the Hh pathway was confirmed in primary cell culture and could be modulated in a manner consistent with a ligand-dependent mechanism. Taken together, these findings suggest that Hh pathway activation is common in pediatric pilocytic astrocytomas and may be associated with younger age at diagnosis and tumor growth. © The Author(s) 2010.
Tinker C.,Ingram Medical
Omega (United States) | Year: 2013
Songs from the Heart is an annual palliative care and outreach/support project done in partnership with the Vanderbilt-Ingram Cancer Center Henry Joyce Cancer Clinic and Gilda's Club Nashville. It is a two-evening songwriters' workshop and concert that gives cancer survivors, family members and healthcare professionals the opportunity to tell their story about cancer through the art of music in a safe therapeutic environment. It is a unique project through the art of music helping others of all ages and from all walks of life find healing and hope; as well as an opportunity to give back to others. A professional singer/songwriter and a social worker co-facilitate the two-evening songwriters workshop. Two musicians perform songs the workshop songwriters have written at a community wide concert. Those who have participated in Songs from the Heart have communicated through the workshop evaluations that this experience has been life changing and a unique opportunity in being able to: explore and express their deep felt emotional feelings and thoughts; release their creative juices; ability to be alone with the group, yet feel included as a whole; express their journey through music; and benefit from being involved with others affected by cancer who have had similar difficulties. Others who have attended the concert or listened to the CD have expressed the significant impact these songs have had on their lives and their journey with cancer. © 2013, Baywood Publishing Co., Inc.
News Article | September 5, 2013
Ingram Medical, a Salt Lake City-based provider of a distribution platform for chronic care products, raised $30m in Series B funding. The round was led by Mercato Partners, with participation from Intermountain Healthcare and StepStone Group. The company intends to use the funds to expand in other chronic care groups. Led by Jeff Smith, CEO, Ingram Medical provides home-delivered, diabetic testing supplies, serving customers nationwide and operates an online Diabetes Health Center, which offers quality information developed by a staff of expert nurses, nutritionists, educators, and physicians.
Sengsayadeth S.M.,Ingram Medical |
Jagasia M.,Ingram Medical |
Engelhardt B.G.,Ingram Medical |
Kassim A.,Ingram Medical |
And 6 more authors.
Bone Marrow Transplantation | Year: 2012
Seventy-nine patients with AML in CR1 received allo-SCT between May 2006 and May 2011, and the prognostic impact of FMS-like tyrosine kinase 3/internal tandem duplication (FLT3/ITD) mutation was evaluated in the context of other clinical prognostic factors. Patients with FLT3/ITD+ AML had significantly inferior DFS (2-year DFS: 19% vs 64%, P=0.0027), increased risk of relapse (1-year: 59% vs 19%, P=0.01), and a trend towards decreased OS (P=0.08) compared with patients without FLT3/ITD. Multivariate analysis confirmed FLT3/ITD+ independently predicted a shorter DFS (HR, 3.0; 95% CI), 1.4-6.5; P=0.01) and increased risk of relapse (HR, 4.9; 95% CI, 2.0-12.3, P=0.01). Time to relapse in patients with FLT3/ITD+ was short with 100-day cumulative risk of 45% (95% CI, 33-57). Our data suggest that the poor prognostic implication of FLT3/ITD positivity remains even after early allo-SCT in patients with FLT3/ITD+ AML, and patients remain at high risk of early relapse. FLT3/ITD positivity also outweighs other conventional prognostic markers in predicting relapse. © 2012 Macmillan Publishers Limited.