- Email: [email protected]
▪ FEATURED ABSTRACT Inhibition of HIF-1 alpha induced survival under hypoxic conditions in liver cancer cells
JVIR
’
Scientific Session
4:12 PM
Sunday
Abstract No. 37
Quality assurance post-UAE for symptomatic fibroids and adenomyosis: a multi-parametric analysis and long-term quality-of-life assessment
Purpose: Though the immediate quality-of-life benefits of UAE are known, long-term benefits and follow-up guidelines are less well established. This aim of this study was to ensure quality of long-term (4-6 years) symptom improvement postUAE and identify predictors of positive long-term results Materials: This retrospective, IRB approved study was conducted in 20 subjects (mean age; 46.7 years) who underwent UAE between January 1st, 2008 and December 31st, 2010. Cases were selected based on availability of pre- and post-procedure (4 months) MRI and uterine fibroid symptom quality-of-life questionnaires (UFS-QoL). The questionnaires established symptom severity scores and health related quality-oflife (HRQoL) scores. Eligible subjects were requested to complete a long-term QoL questionnaire. Univariate analyses (Spearman correlation) and multivariate analyses (linear regression) were conducted to examine the association/correlation between longterm outcomes of interest (% change in symptom severity score and HRQoL at 4-6 years) and candidate factors (MRI parameters and UFS-QoL pre- and post-UAE). Results: Significant correlation was found between change in symptom severity at 4-6 years and largest fibroid volume pre-UAE (ρ¼-0.45, po0.05) and largest fibroid volume at 4 months (ρ¼0.48, po0.05). Significant correlation was found between change in HRQoL at 4-6 years and age at UAE (ρ¼0.56, po0.05), HRQoL Pre (ρ¼-0.74, po0.05) and HRQoL at 4 months (ρ¼-0.55, po0.05). The final regression model for change in symptom severity at 4-6 years included: age, symptom severity at 4 months and change in symptom severity at 4 months. The final model for change in HRQoL at 4-6 years included: age, HRQoL Pre, HRQoL at 4 months and change in HRQoL at 4 months. Conclusions: This study establishes the largest fibroid volume as a predictor of change in symptom severity at 4-6 years postUAE. Change in HRQoL score at 4 months is a predictor of change in HRQoL Score at 4-6 years. This finding may serve as an important tool in determining necessity of clinical follow-up beyond 4 months. Future studies may enroll a larger patient cohort and further validate the long-term QoL questionnaire.
4:21 PM
S21
uterine fibroid embolization (UFE) has been shown to be safe and feasible for patients with radial artery (RA) diameters greater than or equal to 3 mm. Yet, the average female left RA is well below 3 mm in size. This study examines the safety and efficacy of UFE via TRA in patients with RA calibers of 2 to 3 mm. Materials: All patients with left RA diameters of 2.0 to 3.0 mm who underwent UFE were retrospectively reviewed. Each patient reported uterine fibroid symptoms such as menorrhagia, dysmenorrhea, bulk sensation, and dyspareunia. RA caliber was measured under direct sonography. In all cases, a Barbeau test was performed. A 4-Fr Glidesheath (Terumo Medical Corporation, Somerset, NJ) was placed in the left RA using ultrasound guidance. Following sheath placement, intraarterial administration of heparin (3000 units), verapamil (2.5 mg), and nitroglycerin (200 mcg) was performed. Technical success and major/minor complications were recorded. RA patency was evaluated immediately post-operatively, at the time of discharge, and at 5-weeks via palpation of the pulse. Patient satisfaction at the 5-week follow up visit was also assessed. Results: From 10/2013 to 8/2015, a total of 60 UFE procedures were performed in patients whose left RA measured 2.0 to 3.0 mm (mean 2.4 mm). 100% of our patients had RA diameters 4 sheath caliber. Technical success was 100%. There were no major adverse events. There were two minor adverse events: intra-operative RA vasospasm and ecchymosis around a puncture site. The latter event was asymptomatic and managed conservatively. There were no additional adverse events at 5 weeks. The RA were patent at all checkpoints (postoperatively, at time of discharge, and at 5-week follow-up) for all subjects. Each patient reported significant improvement at the 5-week follow-up. Conclusions: In this retrospective single center review, transradial UFE in female patients with left RA diameters of 2.0 to 3.0 mm is safe and effective for treating symptomatic uterine fibroids with minimal peri-operative complications.
Scientific Session 5 IO: Basic Science Sunday, April 3, 2016 3:00 PM – 4:30 PM Room: 119/120
Abstract No. 38
Safety and efficacy of transradial uterine fibroid embolization via small caliber arterial access
3:00 PM
S. Pham1, J. Arampulikan2, D. Ruiz3, N. Resnick4; 1Harlem Hospital Center, New York City, NY; 2Lincoln Medical Center, Bronx, NY; 3Harlem Hospital Center- Columbia, New York, NY; 4Harlem Hospital Center, New York city, NY
’ FEATURED ABSTRACT Inhibition of HIF-1 alpha induced survival under hypoxic conditions in liver cancer cells
Purpose: Transradial access (TRA) is being increasingly used to perform visceral and peripheral interventions. TRA for
Abstract No. 39
V. Gogineni1, S. White1; 1Medical College of Wisconsin, Milwaukee, WI.
SUNDAY: Scientific Sessions
A. Gotra1, M. Robichaud1, C. Tardif1, P. Delli Fraine1, A. Bessissow2, V. Demers3, L. Boucher1, D. Valenti1; 1 McGill University Health Centre, Montreal, QC; 2Centre Hospitalier de l’Université de Montréal, Montreal, QC; 3 N/A, Boucherville, QC
’
SUNDAY: Scientific Sessions
S22
’
Sunday
Scientific Session
Purpose: In our previous studies we have shown that stabilization of HIF-1a under hypoxic conditions is essential to show its downstream activities in vitro and in vivo. Transarterial chemoembolization induced hypoxia triggers a series of pro-metastatic molecular events in liver tumors leading to the escape of tumor cells into circulation and exacerbates the prognosis. The purpose of our study was to evaluate whether HIF-1a inhibitors sensitize cells and induce death in hypoxic conditions in hepatocellular carcinoma (HCC) or colorectal liver metastases (CRLM) cell lines in vitro. Materials: 1*104 rat HCC cell lines, N1S1 and MCA, a CRLM cell line (CC-531) and a normal hepatocyte cell line (clone 9) were plated in a 96 well plate in triplicate. The cells were exposed to hypoxic conditions (1% O2, 5%CO2 and 95%N2) for up to 72 hours. Cellular viability was determined with trypan blue staining at 24h intervals. Expression of HIF-1a and VEGF was assessed under hypoxic conditions using quantitative ELISA and different inhibitors (LW6, YC1 and R59949) targeting HIF-1a were tested at 10-20uM concentrations. Further, a dose dependent survival response to R59949 inhibitor at 20-50uM concentrations was studied to determine optimal conditions. Results: All cell line showed greater than 90% survival rates at up to 72h. Clone 9 cells demonstrated similar patterns of growth in hypoxic conditions. HIF-1a and VEGF were found to increase significantly in hypoxic cell lysates and conditioned media respectively. Further, when the cells were treated with the HIF-1a inhibitors, the growth was reduced by almost half under hypoxic conditions. R59949 was found to be most effective inhibitor among the three tested inhibitors on different cell lines. Cells treated with increasing dose of R59949 have showed more than 90% reduction in growth within 48h at 40uM concentration compared to untreated and normoxic cells under the similar conditions of growth. Conclusions: HCC and CRLM cells survive under hypoxic conditions by the expression of HIF-1a and inhibition of HIF-1a sensitizes cells and induces death. In vivo studies on inhibitors in combination with TACE could prove very effective in the management of liver tumors.
’
JVIR
been utilized to develop compounds that target folate receptors to identify cancerous cells and drug delivery. The purpose of this study was to test the targeting efficiency and cytotoxicity of a novel folate targeting nanomolecule. Materials: 1.5 x 10∧6 breast cancer cells MDA-MB-468 (low FR expression) and MDA-MB-231(high FR expression) were grown in low folate culture media (MEM/EBS NEAA). When the cells were 70 % confluent, they were treated with 5ug, 10ug and 30ug of the Compound FA-FL-FA, for 2 hours. Cells were stained with 10ug/ml propidium iodide (PI) for 15 min to detect dead or injured cells. Cell viability and compound uptake was estimated by flow cytometry (BD, LSR II), using an Argon laser and an excitation energy of 480 nm. Proc GLIMMIX in SAS version 9.2 was used for statistical analysis. All experiments were repeated 7 times (N¼7). Linear correlation was used to determine the dose response of drug uptake by FITC expression and cytotoxicity by PI staining. Results: A dose dependent uptake of compound was observed in both cell lines. MDA-MB-231 cell line had 62.46% uptake of 5ug compound, 85.86% uptake of 10ug and 93.66% uptake of 30ug compound. MDA-MB-468 cell line had 9.58% uptake in 5 ug compound dose, 36.63% uptake in 10ug compound dose and 53.2% uptake in 30ug compound dose. MDA-MB-231 cell line was viable at all doses of compound and no cytotoxicity was noted. In comparison, there was about 20% cytotoxicity with 30ug dose in MDA-MB-468 cell line, however, no significant cytotoxicity was observed with 5ug or 10ug doses. Conclusions: Both cell lines demonstrated greater uptake of compound with increased compound doses. There was an expected better uptake of the compound to the cell line with more folate receptors with no significant cytotoxicity. In order to assess specificity and bioavailability of the compound in-vivo, more experiments need to be done particularly in the animal model. References 1. Kelemen EL. The role of folate receptor alpha in cancer development, progression and treatment: cause, consequence or innocent bystander? Int J Cancer. 2006; 119(2):243–250. 2. Yamaguchi T1, Hirota K, Nagahama K, Ohkawa K, Takahashi T, Nomura T, Sakaguchi S. Control of immune responses by antigen-specific regulatory T cells expressing the folate receptor. Immunity 2007; 27(1):145–59. Epub 2007 Jul 5.
References 1. Yu F, White SB, Zhao Q, Lee FS. Dynamic, site-specific interaction of hypoxia-inducible factor-1alpha with the von Hippel-Lindau tumor suppressor protein. Cancer research 2001; 61(10):4136–4142. 2. Yu F, White SB, Zhao Q, Lee FS. HIF-1alpha binding to VHL is regulated by stimulus-sensitive proline hydroxylation. Proceedings of the National Academy of Sciences of the United States of America 2001; 98 (17):9630–9635.
3:18 PM
Abstract No. 41
90
Y radiation lobectomy in the rodent model: dosedependent induction of radiation fibrosis and hepatic volume changes in normal liver
N. Khan1, D Das2, G. McLennan3; 1Cleveland Clinic Foundation, Shaker Heights, OH; 2Cleveland Clinic Foundation, Cleveland, OH; 3N/A, Chagrin Falls, OH.
A. Gordon1, S. White2, V. Gates3, D. Procissi3, W. Li3, K. Harris3, D. Kim4, R. Omary5, Z. Zhang3, R. Salem3, R. Lewandowski3, A. Larson3; 1Northwestern University Feinberg School of Medicine, Chicago, IL; 2Medical College of Wisconsin, Northwestern University, Milwaukee, WI; 3Northwestern University, Chicago, IL; 4 Northwestern University/Department of Radiology, Chicago, IL; 5Vanderbilt University Medical Center, Nashville, TN.
Purpose: Neoplastic cells over-express folate receptors (FR) in abundance compared to non-cancerous cells. This property has
Purpose: Radiation lobectomy with yttrium-90 (Y90) is a powerful therapy for downstaging patients with liver-dominant
3:09 PM
Abstract No. 40
Assessment of folate targeting nanomolecule on human cancer cells for cancer drug delivery
’
Scientific Session
4:12 PM
Sunday
Abstract No. 37
Quality assurance post-UAE for symptomatic fibroids and adenomyosis: a multi-parametric analysis and long-term quality-of-life assessment
Purpose: Though the immediate quality-of-life benefits of UAE are known, long-term benefits and follow-up guidelines are less well established. This aim of this study was to ensure quality of long-term (4-6 years) symptom improvement postUAE and identify predictors of positive long-term results Materials: This retrospective, IRB approved study was conducted in 20 subjects (mean age; 46.7 years) who underwent UAE between January 1st, 2008 and December 31st, 2010. Cases were selected based on availability of pre- and post-procedure (4 months) MRI and uterine fibroid symptom quality-of-life questionnaires (UFS-QoL). The questionnaires established symptom severity scores and health related quality-oflife (HRQoL) scores. Eligible subjects were requested to complete a long-term QoL questionnaire. Univariate analyses (Spearman correlation) and multivariate analyses (linear regression) were conducted to examine the association/correlation between longterm outcomes of interest (% change in symptom severity score and HRQoL at 4-6 years) and candidate factors (MRI parameters and UFS-QoL pre- and post-UAE). Results: Significant correlation was found between change in symptom severity at 4-6 years and largest fibroid volume pre-UAE (ρ¼-0.45, po0.05) and largest fibroid volume at 4 months (ρ¼0.48, po0.05). Significant correlation was found between change in HRQoL at 4-6 years and age at UAE (ρ¼0.56, po0.05), HRQoL Pre (ρ¼-0.74, po0.05) and HRQoL at 4 months (ρ¼-0.55, po0.05). The final regression model for change in symptom severity at 4-6 years included: age, symptom severity at 4 months and change in symptom severity at 4 months. The final model for change in HRQoL at 4-6 years included: age, HRQoL Pre, HRQoL at 4 months and change in HRQoL at 4 months. Conclusions: This study establishes the largest fibroid volume as a predictor of change in symptom severity at 4-6 years postUAE. Change in HRQoL score at 4 months is a predictor of change in HRQoL Score at 4-6 years. This finding may serve as an important tool in determining necessity of clinical follow-up beyond 4 months. Future studies may enroll a larger patient cohort and further validate the long-term QoL questionnaire.
4:21 PM
S21
uterine fibroid embolization (UFE) has been shown to be safe and feasible for patients with radial artery (RA) diameters greater than or equal to 3 mm. Yet, the average female left RA is well below 3 mm in size. This study examines the safety and efficacy of UFE via TRA in patients with RA calibers of 2 to 3 mm. Materials: All patients with left RA diameters of 2.0 to 3.0 mm who underwent UFE were retrospectively reviewed. Each patient reported uterine fibroid symptoms such as menorrhagia, dysmenorrhea, bulk sensation, and dyspareunia. RA caliber was measured under direct sonography. In all cases, a Barbeau test was performed. A 4-Fr Glidesheath (Terumo Medical Corporation, Somerset, NJ) was placed in the left RA using ultrasound guidance. Following sheath placement, intraarterial administration of heparin (3000 units), verapamil (2.5 mg), and nitroglycerin (200 mcg) was performed. Technical success and major/minor complications were recorded. RA patency was evaluated immediately post-operatively, at the time of discharge, and at 5-weeks via palpation of the pulse. Patient satisfaction at the 5-week follow up visit was also assessed. Results: From 10/2013 to 8/2015, a total of 60 UFE procedures were performed in patients whose left RA measured 2.0 to 3.0 mm (mean 2.4 mm). 100% of our patients had RA diameters 4 sheath caliber. Technical success was 100%. There were no major adverse events. There were two minor adverse events: intra-operative RA vasospasm and ecchymosis around a puncture site. The latter event was asymptomatic and managed conservatively. There were no additional adverse events at 5 weeks. The RA were patent at all checkpoints (postoperatively, at time of discharge, and at 5-week follow-up) for all subjects. Each patient reported significant improvement at the 5-week follow-up. Conclusions: In this retrospective single center review, transradial UFE in female patients with left RA diameters of 2.0 to 3.0 mm is safe and effective for treating symptomatic uterine fibroids with minimal peri-operative complications.
Scientific Session 5 IO: Basic Science Sunday, April 3, 2016 3:00 PM – 4:30 PM Room: 119/120
Abstract No. 38
Safety and efficacy of transradial uterine fibroid embolization via small caliber arterial access
3:00 PM
S. Pham1, J. Arampulikan2, D. Ruiz3, N. Resnick4; 1Harlem Hospital Center, New York City, NY; 2Lincoln Medical Center, Bronx, NY; 3Harlem Hospital Center- Columbia, New York, NY; 4Harlem Hospital Center, New York city, NY
’ FEATURED ABSTRACT Inhibition of HIF-1 alpha induced survival under hypoxic conditions in liver cancer cells
Purpose: Transradial access (TRA) is being increasingly used to perform visceral and peripheral interventions. TRA for
Abstract No. 39
V. Gogineni1, S. White1; 1Medical College of Wisconsin, Milwaukee, WI.
SUNDAY: Scientific Sessions
A. Gotra1, M. Robichaud1, C. Tardif1, P. Delli Fraine1, A. Bessissow2, V. Demers3, L. Boucher1, D. Valenti1; 1 McGill University Health Centre, Montreal, QC; 2Centre Hospitalier de l’Université de Montréal, Montreal, QC; 3 N/A, Boucherville, QC
’
SUNDAY: Scientific Sessions
S22
’
Sunday
Scientific Session
Purpose: In our previous studies we have shown that stabilization of HIF-1a under hypoxic conditions is essential to show its downstream activities in vitro and in vivo. Transarterial chemoembolization induced hypoxia triggers a series of pro-metastatic molecular events in liver tumors leading to the escape of tumor cells into circulation and exacerbates the prognosis. The purpose of our study was to evaluate whether HIF-1a inhibitors sensitize cells and induce death in hypoxic conditions in hepatocellular carcinoma (HCC) or colorectal liver metastases (CRLM) cell lines in vitro. Materials: 1*104 rat HCC cell lines, N1S1 and MCA, a CRLM cell line (CC-531) and a normal hepatocyte cell line (clone 9) were plated in a 96 well plate in triplicate. The cells were exposed to hypoxic conditions (1% O2, 5%CO2 and 95%N2) for up to 72 hours. Cellular viability was determined with trypan blue staining at 24h intervals. Expression of HIF-1a and VEGF was assessed under hypoxic conditions using quantitative ELISA and different inhibitors (LW6, YC1 and R59949) targeting HIF-1a were tested at 10-20uM concentrations. Further, a dose dependent survival response to R59949 inhibitor at 20-50uM concentrations was studied to determine optimal conditions. Results: All cell line showed greater than 90% survival rates at up to 72h. Clone 9 cells demonstrated similar patterns of growth in hypoxic conditions. HIF-1a and VEGF were found to increase significantly in hypoxic cell lysates and conditioned media respectively. Further, when the cells were treated with the HIF-1a inhibitors, the growth was reduced by almost half under hypoxic conditions. R59949 was found to be most effective inhibitor among the three tested inhibitors on different cell lines. Cells treated with increasing dose of R59949 have showed more than 90% reduction in growth within 48h at 40uM concentration compared to untreated and normoxic cells under the similar conditions of growth. Conclusions: HCC and CRLM cells survive under hypoxic conditions by the expression of HIF-1a and inhibition of HIF-1a sensitizes cells and induces death. In vivo studies on inhibitors in combination with TACE could prove very effective in the management of liver tumors.
’
JVIR
been utilized to develop compounds that target folate receptors to identify cancerous cells and drug delivery. The purpose of this study was to test the targeting efficiency and cytotoxicity of a novel folate targeting nanomolecule. Materials: 1.5 x 10∧6 breast cancer cells MDA-MB-468 (low FR expression) and MDA-MB-231(high FR expression) were grown in low folate culture media (MEM/EBS NEAA). When the cells were 70 % confluent, they were treated with 5ug, 10ug and 30ug of the Compound FA-FL-FA, for 2 hours. Cells were stained with 10ug/ml propidium iodide (PI) for 15 min to detect dead or injured cells. Cell viability and compound uptake was estimated by flow cytometry (BD, LSR II), using an Argon laser and an excitation energy of 480 nm. Proc GLIMMIX in SAS version 9.2 was used for statistical analysis. All experiments were repeated 7 times (N¼7). Linear correlation was used to determine the dose response of drug uptake by FITC expression and cytotoxicity by PI staining. Results: A dose dependent uptake of compound was observed in both cell lines. MDA-MB-231 cell line had 62.46% uptake of 5ug compound, 85.86% uptake of 10ug and 93.66% uptake of 30ug compound. MDA-MB-468 cell line had 9.58% uptake in 5 ug compound dose, 36.63% uptake in 10ug compound dose and 53.2% uptake in 30ug compound dose. MDA-MB-231 cell line was viable at all doses of compound and no cytotoxicity was noted. In comparison, there was about 20% cytotoxicity with 30ug dose in MDA-MB-468 cell line, however, no significant cytotoxicity was observed with 5ug or 10ug doses. Conclusions: Both cell lines demonstrated greater uptake of compound with increased compound doses. There was an expected better uptake of the compound to the cell line with more folate receptors with no significant cytotoxicity. In order to assess specificity and bioavailability of the compound in-vivo, more experiments need to be done particularly in the animal model. References 1. Kelemen EL. The role of folate receptor alpha in cancer development, progression and treatment: cause, consequence or innocent bystander? Int J Cancer. 2006; 119(2):243–250. 2. Yamaguchi T1, Hirota K, Nagahama K, Ohkawa K, Takahashi T, Nomura T, Sakaguchi S. Control of immune responses by antigen-specific regulatory T cells expressing the folate receptor. Immunity 2007; 27(1):145–59. Epub 2007 Jul 5.
References 1. Yu F, White SB, Zhao Q, Lee FS. Dynamic, site-specific interaction of hypoxia-inducible factor-1alpha with the von Hippel-Lindau tumor suppressor protein. Cancer research 2001; 61(10):4136–4142. 2. Yu F, White SB, Zhao Q, Lee FS. HIF-1alpha binding to VHL is regulated by stimulus-sensitive proline hydroxylation. Proceedings of the National Academy of Sciences of the United States of America 2001; 98 (17):9630–9635.
3:18 PM
Abstract No. 41
90
Y radiation lobectomy in the rodent model: dosedependent induction of radiation fibrosis and hepatic volume changes in normal liver
N. Khan1, D Das2, G. McLennan3; 1Cleveland Clinic Foundation, Shaker Heights, OH; 2Cleveland Clinic Foundation, Cleveland, OH; 3N/A, Chagrin Falls, OH.
A. Gordon1, S. White2, V. Gates3, D. Procissi3, W. Li3, K. Harris3, D. Kim4, R. Omary5, Z. Zhang3, R. Salem3, R. Lewandowski3, A. Larson3; 1Northwestern University Feinberg School of Medicine, Chicago, IL; 2Medical College of Wisconsin, Northwestern University, Milwaukee, WI; 3Northwestern University, Chicago, IL; 4 Northwestern University/Department of Radiology, Chicago, IL; 5Vanderbilt University Medical Center, Nashville, TN.
Purpose: Neoplastic cells over-express folate receptors (FR) in abundance compared to non-cancerous cells. This property has
Purpose: Radiation lobectomy with yttrium-90 (Y90) is a powerful therapy for downstaging patients with liver-dominant
3:09 PM
Abstract No. 40
Assessment of folate targeting nanomolecule on human cancer cells for cancer drug delivery