Inhibition of ADAM9 expression induces epithelial phenotypic alterations and sensitizes human prostate cancer cells to radiation and chemotherapy.

INTRODUCTION: Recent studies demonstrated the importance of ADAM9 in prostate cancer relapse upon therapy. In this study, we determined the role of ADAM9 in the therapeutic resistance to radiation and chemotherapy. MATERIALS AND METHODS: ADAM9 was either transiently or stably knocked down in C4-2 prostate cancer cells. The sensitivity of ADAM9 knockdown cells toward radiation and chemotherapeutic agents were determined. Additionally, the effects of ADAM9 knockdown on prostate cancer cell morphology, biochemical and functional alterations were accessed. RESULTS: Both transient and stable knockdown of ADAM9 resulted in increased apoptosis and increased sensitivity to radiation. ADAM9 knockdown also increased prostate cancer sensitivity to several chemotherapeutic drugs. ADAM9 knockdown resulted in increased E-cadherin and altered integrin expression and underwent phenotypic epithelial transition. These were reflected by the morphological, biochemical, and functional alterations in the ADAM9 knockdown cells. CONCLUSIONS: ADAM9 plays a crucial role in prostate cancer progression and therapeutic resistance in part by altering E-cadherin and integrin expression. ADAM9 is an important target for the consideration of treating prostate cancer patients who developed therapeutic resistance and disease relapse.

Role of FDG-PET in the definition of involved-field radiation therapy and management for pediatric Hodgkin's lymphoma.

PURPOSE: To evaluate positron emission tomography-computed tomography (PET-CT) influences in involved-field radiation therapy (IFRT) field design in pediatric Hodgkin's lymphoma (HL). MATERIALS AND METHODS: From June 2003 to February 2008, 30 pediatric HL patients were treated at Children's Healthcare of Atlanta (CHOA) and Emory University Department of Radiation Oncology with both chemotherapy and IFRT. Diagnostic contrast-enhanced CT and PET-CT were coregistered using image fusion software. Both were reviewed for all potential sites of involvement and correlated to determine concordance and discordance. They were used in IFRT planning to determine the influence of PET-CT on target volumes and field design. RESULTS: There were 546 regions analyzed by both PET and CT modalities. Image sets were concordant in 468 regions and discordant in 78, yielding 86% concordance overall. Analysis by weighted κ statistic showed "intermediate to good" fit overall and for nodal sites, but "poor" agreement for extranodal sites. If discordant, a site was most likely PET+/CT-. Integration of PET information caused a change in staging in 15 (50%) patients, 7 upstaged and 8 downstaged. The IFRT volumes were adjusted on the basis of initial PET-CT finding in 21 (70%) patients, with 32 sites added and 15 excluded. There were four relapses, only one outside IFRT fields, but all were successfully salvaged. CONCLUSION: PET-CT represents an important tool in the management of pediatric patients with HL and has a substantial influence on both initial staging and radiation treatment target definition and field design.

Combined modality therapy for stage III non-small-cell lung cancer.

With 40,000 to 50,000 patients diagnosed annually, stage III lung cancer represents approximately one third of all non-small-cell lung cancer cases. It is a heterogeneous disease stage encompassing stage IIIa, for which surgery in combination with chemotherapy and/or radiation therapy represents a treatment strategy for select patients, and stage IIIb, for which chemoradiation represents the prevailing standard of care. Overcoming unacceptably high rates of intrathoracic tumor failures remains a central obstacle. Current clinical trial efforts focus on targeted therapies, new chemotherapy regimens, dose-escalated radiation therapy, and improvements in radiation therapy treatment delivery.