ABSTRACT
PURPOSE: In this study, we first aimed to evaluate the effects in vitro and in vivo, of the Hsp90 inhibitor NVP-AUY922, in endometrial cancer (EC). We also aimed to track nuclear factor kappa B (NF-κB) signalling, a key pathway involved in endometrial carcinogenesis and to check whether NVP-AUY922 treatment modulates it both in vitro and in vivo. PROCEDURES: I n vitro effects of NVP-AUY922 on EC cell growth and the signalling pathways were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), clonogenic assays, Western Blot and luciferase assay. NVP-AUY922 effect on Ishikawa (IK) xenograft growth was evaluated in vivo, and NF-κB activity was monitored using bioluminescence imaging. RESULTS: NVP-AUY922 inhibited the growth of three endometrial cell lines tested in vitro. In vivo, NVP-AUY922 reduced tumour growth of 47 % (p = 0.042) compared to control condition. Moreover, the bioluminescence signal of the tumours harbouring IK NF-κB-LUC cells was significantly reduced in NVP-AUY922-treated animals compared to untreated ones. CONCLUSIONS: NVP-AUY922 reduced EC tumour growth and NF-κB signalling both in vitro and in vivo. As therapeutic resistance of EC remains a challenge for oncologists nowadays, we think that NVP-AUY922 represents a valid alternative to conventional chemotherapy, and we believe that this approach for assessing and tracking the activation of NF-κB pathway may be of therapeutic benefit.
Subject(s)
Diagnostic Imaging/methods , Endometrial Neoplasms/diagnosis , HSP90 Heat-Shock Proteins/antagonists & inhibitors , Isoxazoles/pharmacology , Luminescent Measurements/methods , NF-kappa B/metabolism , Resorcinols/pharmacology , Signal Transduction/drug effects , Animals , Apoptosis/drug effects , Cell Cycle Checkpoints/drug effects , Cell Hypoxia/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Clone Cells , Endometrial Neoplasms/pathology , Female , HSP70 Heat-Shock Proteins/metabolism , HSP90 Heat-Shock Proteins/metabolism , Humans , Luciferases/metabolism , Mice , Xenograft Model Antitumor AssaysABSTRACT
AIM: To evaluate the resources and techniques used in the irradiation of patients with breast cancer after lumpectomy or mastectomy and the status of implementation of new techniques and therapeutic schedules in our country. BACKGROUND: The demand for cancer care has increased among the Spanish population, as long as cancer treatment innovations have proliferated. Radiation therapy in breast cancer has evolved exponentially in recent years with the implementation of three-dimensional conformal radiotherapy, intensity modulated radiotherapy, image guided radiotherapy and hypofractionation. MATERIAL AND METHODS: An original survey questionnaire was sent to institutions participating in the SEOR-Mama group (GEORM). In total, the standards of practice in 969 patients with breast cancer after surgery were evaluated. RESULTS: The response rate was 70% (28/40 centers). In 98.5% of cases 3D conformal treatment was used. All the institutions employed CT-based planning treatment. Boost was performed in 56.4% of patients: electrons in 59.8%, photons in 23.7% and HDR brachytherapy in 8.8%. Fractionation was standard in 93.1% of patients. Supine position was the most frequent. Only 3 centers used prone position. The common organs of risk delimited were: homolateral lung (80.8%) and heart (80.8%). In 84% histograms were used. An 80.8% of the centers used isocentric technique. In 62.5% asymmetric fields were employed. CTV was delimited in 46.2%, PTV in 65% and both in 38.5%. A 65% of the centers checked with portal films. IMRT and hypofractionation were used in 1% and in 5.5% respectively. CONCLUSION: In most of centers, 3D conformal treatment and CT-based planning treatment were used. IMRT and hypofractionation are currently poorly implemented in Spain.
ABSTRACT
PURPOSE: To study whether orgotein is effective in preventing late radiation-induced effects. METHODS AND MATERIALS: Patients >18 years old who were diagnosed with rectal cancer, had an indication for pelvic irradiation (RT) after surgery, and complied with the selection criteria were randomly assigned at the end of RT to receive orgotein for 7 weeks or no treatment (control). The Radiation Therapy Oncology Group toxicity scale was used to evaluate the RT-induced side effects for up to 2 years. Interruptions due to toxicity, concomitant medication, and non-RT adverse events were also recorded. RESULTS: A total of 100 patients were included, with 50 in each group. The groups were comparable in terms of the demographic and baseline characteristics. The orgotein group had statistically significant less late toxicity than the control group (p = 0.036) and nontreated patients had a 66% greater chance of developing late toxicity at 2 years. Grouping toxicity as nonrelevant (Radiation Therapy Oncology Group Grade 0-1) and relevant (Grade 2 or worse), patients given orgotein had a lower incidence of late relevant toxicity than did controls, with statistical significance reached at all follow-up visits. After 2 years, patients not treated with orgotein had, in general, a 37% greater chance of developing late relevant toxicity; this risk was 26% when referring specifically to GI toxicity. No adverse events attributable to orgotein were recorded at any time during the study. CONCLUSION: Orgotein is a safe treatment that significantly prevents the overall occurrence of late toxicity, with toxicity reduction particularly evident in the lower GI tract.
