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P0184 Establishment of a cell microencapsulation model using mucoepidermoid carcinoma cells
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Abstracts / 51 (2015) e1–e36
the patients surveyed had poor quality of life. Importantly, no scale was used for pain assessment in 49% of the patients. Opioids were prescribed to some patients only. This survey indicated a critical need to enhance cancer pain management via adequate assessment and therapy optimisation.
http://dx.doi.org/10.1016/j.ejca.2015.06.098
P0176 DOSIMETRIC COMPARISON OF VOLUMETRIC INTENSITY-MODULATED ARC (RAPIDARC) THERAPY, INTENSITY-MODULATED RADIOTHERAPY, AND 3D CONFORMAL RADIOTHERAPY FOR PRIMARY LIVER TUMOURS Jacob John a,*, Roshni Sivasevan a, Arun Sankar Sudha a, Choondal Devan Sivanandan a, Sajeed Abdurahman a, Raghukumar Paramu b, Shaiju Vasudevan Sreedevi b, Preethi Sara George c, Puthuveettil Govindan Jayaprakash a. a Division of Radiation Oncology, Regional Cancer Centre, Thiruvananthapuram, India, b Division of Radiation Physics, Regional Cancer Centre, Thiruvananthapuram, India, c Division of Epidemiology and Biostatistics, Regional Cancer Centre, Thiruvananthapuram, India Background: To compare the dosimetric outcomes of volumetric arc radiotherapy (RapidArc), intensity-modulated radiotherapy (IMRT), and 3D conformal radiotherapy (3DCRT) plans for primary liver tumours. Methods: 7 patients with localised unresectable hepatocellular carcinoma were included in this study. CT simulation was done with voluntary deep inspiratory breath-holding after administering 80–90 mL of intravenous iodinated contrast. The mean tumour size was 5.6 cm (range 2.1–9.8) and two patients had multiple lesions (range 1–3). All patients were planned for partial liver irradiation for a total dose of 50–66 Gy in 2 Gy per fraction with conformal techniques. 3DCRT, IMRT, and RapidArc plans were generated using Eclipse planning system v.13 and dosimetric analysis was done to evaluate the plan quality and efficiency, including CI, HI, MU delivered, PTV Dmean and Dmax. IMRT plans had 3–5 fields and RapidArc plans had 3–5 arcs. V10,V20,V30 and V40 of normal liver and Dmean of organs at risk (OAR) and Dmax of spinal cord were also evaluated. Analysis was done using ANOVA and paired t-test with two tailed p < 0.05. Findings: All the three techniques had comparable PTV coverage, dose homogeneity, and OAR sparing. IMRT and Rapid Arc had a significantly better conformity index than 3DCRT (p = 0.03). The high dose areas within the normal liver; V40 and V30 were significantly lower in RapidArc and IMRT plans (p = 0.03 and p = 0.04, respectively), although no significant differences were noted between IMRT and RapidArc. One patient could not attain the normal liver constraint V33 <33 Gy, which was attained with both IMRT and RapidArc plans. Interpretation: RapidArc and IMRT provide better normal liver sparing and conformity than 3DCRT. However, RapidArc was not better than IMRT for liver protection. Further large trials are required to clearly establish the benefits of IMRT and Rapid Arc techniques to treat primary liver tumours.
http://dx.doi.org/10.1016/j.ejca.2015.06.099
P0180 EFFECT OF PIOGLITAZONE ON PROLIFERATION AND APOPTOSIS IN HUMAN UTERINE LEIOMYOSARCOMA CELLS Yi Zhao a,*, Katja Lucht b, Maaz Zuhayra a, Ingolf Cascorbi b, Ulf a Lu¨tzen a, Juraj Culman b. Department of Nuclear Medicine, Molecular Imaging, Diagnostics and Therapy, University Hospital of Schleswig-Holstein, Kiel, Germany, b Institute of Experimental and Clinical Pharmacology, University Hospital of Schleswig-Holstein, Kiel, Germany Background: SK-UT-1 cells, a human uterine leiomyosarcoma cell line, and human uterine smooth muscle cells (HutSMC) (controls) express the peroxisome proliferator-activated receptor c (PPARc). We investigated the effects of the PPARc agonist pioglitazone on the proliferation and induction of apoptosis in SK-UT-1 cells and HutSMC. Methods: Cells were exposed to pioglitazone (10 or 25 lmol/l) in the presence or absence of the selective PPARc antagonist, GW 9226 (1 lmol/l). Cell proliferation was evaluated by WST-1 assay and cresyl violet staining. Western blot analysis was used to quantify the cleaved caspase-3, Bax, and Bad proteins. Cellular toxicity of pioglitazone was assessed by lactate dehydrogenase (LDH) release. Findings: Pioglitazone increased the expression of the PPARc in SK-UT-1 cells and in HutSMC by a PPARc-dependent mechanism. Pioglitazone reduced cell proliferation in both quiescent and proliferating SK-UT-1 cells in concentration and time dependent fashion. These effects were partially mediated by PPARc. In SK-UT-1 cells, pioglitazone (25 lmol/l) activated caspase-3 and induced Bad, Bax, and p53 proteins. Higher levels of MEK and ERK and p-MEK and p-ERK were detected in quiescent SK-UT-1 cells than in quiescent HutSMC. Pioglitazone reduced p-ERK and p-MEK in SK-UT-1 cells in a time dependent manner, but did not alter p-MEK/MEK and p-ERK/ERK levels in HutSMC. Pioglitazone did not exert any cytotoxic effects in SK-UT-1 or HutSMC. Interpretation: We demonstrate that pioglitazone reduces proliferation and promotes apoptosis in quiescent and proliferating leiomyosarcoma cells.
http://dx.doi.org/10.1016/j.ejca.2015.06.100
P0184 ESTABLISHMENT OF A CELL MICROENCAPSULATION MODEL USING MUCOEPIDERMOID CARCINOMA CELLS Li-juan Guo a, Xiong-fei Pan b, Sen Yang c,*, Wings Ty Loo d,e, Louis W C Chow d, William Tsang e. a Medical Beauty Department, Suining Central Hospital, Suining, China, b Department of Epidemiology, West China School of Public Health, Sichuan University, Chengdu, China, c Department of Stomatology, Suining Central Hospital, Suining, China, d UNIMED Medical Institute and Organisation for Oncology and Translational Research, Hong Kong, e Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hong Kong Background: Adherent cell culturing is a mature cell culturing technique mainly used for research on molecular mechanism of biological function of adherent cells. Specifically, it is widely applied in studies of cancer onset and development, and of the action of pharmaceutical
Abstracts / 51 (2015) e1–e36
agents on cancer cells. Cell microencapsulation is a technique by which cells are encapsulated in a semi-permeable microcapsule and live like those in physiological conditions with normal nutritional supply. It is a culturing technique that ranks between monolayer and three-dimensional culture. With microencapsulation, adherent cells grow in a three dimensional manner, and its metabolism and genetic expression also change, similar to solid tumours. Methods: We aimed to establish a cell microencapsulation model using human mucoepidermoid carcinoma cells (MCCs), and assess the cell culture model based on cell growth characteristics, proliferation activity, and protein expression. After MCCs had been isolated and cultured in RPMI-1640 medium, cell growth characteristics, proliferation activity, and protein expression of microencapsulated MCCs and conventional adherent MCCs (as control) were compared. Findings: Results showed MCCs in microcapsules grew in blocks with favourable proliferation activity. On day 3, the cell count in the microencapsulation group was significantly higher than the control group (t = 0.480, p < 0.05). On day 7, cell proliferation had not reached a plateau or declined. Compared with adherent MCCs, microencapsulated MCCs showed significantly higher expression of vascular endothelial growth factor (VEGF) and bFGF (t = 7.617, p < 0.01; t = 6.011, p < 0.01), while TSP-1 was significantly less expressed (t = 12.45, p < 0.001). Interpretation: Microencapsulation culture may help to establish three-dimensional growth of tumour cells in vitro that promote protein expression for angiogenesis. It may be a promising model for functional research of tumour-related genes. In addition, it may be used in studies on biological characteristics of tumour cells and screening of antitumour pharmaceuticals. It will also have prospect in the in situ amplification of stem cells due to convenient inoculation and collection.
http://dx.doi.org/10.1016/j.ejca.2015.06.101
P0191 HISTOGRAM ANALYSIS OF APPARENT DIFFUSION COEFFICIENTS AFTER NEOADJUVANT CHEMOTHERAPY IN BREAST CANCER S.H. Kim *, Y.J. Kim. The Catholic University of Korea, Republic of Korea Background: The purpose of our study was to evaluate change of the apparent diffusion coefficient (ADC) histogram during the neoadjuvant chemotherapy (NAC) in breast cancer, and to compare changes between pathologically verified responders and non-responders. Methods: 62 patients received NAC followed by surgery. We defined responders and non-responders based on 30% reduction in tumour cells using the Miller-Payne Grading System. All patients underwent 3T magnetic resonance (MR) with diffusion-weighted imaging (DWI) before the NAC and after the completion of two cycles of NAC. ADC histogram analysis encompassing the entire tumour was performed and various ADC parameters (mean, minimum, 10th, 25th, 50th, 75th, 90th percentile, maximum ADCs, skewness, and kurtosis) were obtained. Findings: Mean, minimum, 10th, 25th, 50th, and 75th percentile ADCs significantly increased after NAC (p = 0.0129, p = 0.0004, p = 0.0047, p = 0.0002, p = 0.0006, p = 0.0030) and maximum ADC significantly decreased (p = 0.0003). Skewness changed into less positive (p < 0.0001) and kurtosis decreased (p = 0.0168) after NAC. Although there was no statistical significance, mean, minimum, 10th,
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25th, 50th, 75th, and 90th percentile ADCs tended to decrease more in responders compared with non-responders. Interpretation: There is significant change in distribution of ADC after NAC. ADC histogram analysis quantitatively demonstrates the alterations more precisely during the treatment course. http://dx.doi.org/10.1016/j.ejca.2015.06.102
P0192 SENTINEL NODE BIOPSY IN BREAST CANCER USING ONLY METHYLENE BLUE DYE: A PROSPECTIVE STUDY IN A RURAL TERTIARY CARE CENTRE R. Shah *, S. Virani, S. Shah. Kailash Cancer Hospital and Research Centre, Vadodara, India Background: Breast carcinoma is the most common malignancy in women and is the leading cause of death in their middle age. Sentinel lymph node biopsy (SLNB) is a reliable and minimally invasive diagnostic method to determine the regional nodal status in breast cancer and provides accurate staging, such that axillary lymph node dissection can be avoided in negative sentinel node patients. The aim of this study was to assess SLNB, using methylene blue dye, and its accuracy. The complications of using methylene blue dye were also studied. Methods: 138 patients with breast cancer were subjected to SLNB (using methylene blue dye) followed by complete axillary lymph node dissection. The lymph nodes with positive dye were identified. The dye was injected 30 min prior to surgery and the stained lymph nodes were identified during dissection. The haemodynamics of the patients was assessed during and after the procedure. Patients were followed up in the post-operative period, and for the final histopathology report, complications such as wound healing and urine discolouration were assessed. Findings: Of 138 patients with dye injected, 124 (89.85%) patients showed stained lymph nodes. Of 124 patients with positive stain, 67 (54.03%) patients showed evidence of malignancy. Of 67 patients with malignancy-positive lymph nodes, 18 patients had positive sentinel node only. In 49 patients, both sentinel and one or more axillary nodes were positive, whereas in 53 patients both nodal statuses were negative. Four patients had negative sentinel node and positive axillary node. All 14 patients in whom sentinel node could not be identified were negative for cancer in axillary nodes. Seven patients had minor dye-related complications. Interpretation: SLNB with methylene blue dye alone can be considered in breast carcinoma as a reliable, accurate, cost effective, and safe method to detect lymph node status. http://dx.doi.org/10.1016/j.ejca.2015.06.103
P0193 MARSDENIA TENACISSIMA EXTRACT ENHANCES GEFITINIB EFFICACY IN NON-SMALL-CELL LUNG CANCER XENOGRAFTS Shu-Yan Han a,b, Wei Zhao a,c, Hong Sun a,b, Ning Zhou a,b, Fei a Zhou a,b, Guo An a,d, Ping-Ping Li a,b. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China,
Abstracts / 51 (2015) e1–e36
the patients surveyed had poor quality of life. Importantly, no scale was used for pain assessment in 49% of the patients. Opioids were prescribed to some patients only. This survey indicated a critical need to enhance cancer pain management via adequate assessment and therapy optimisation.
http://dx.doi.org/10.1016/j.ejca.2015.06.098
P0176 DOSIMETRIC COMPARISON OF VOLUMETRIC INTENSITY-MODULATED ARC (RAPIDARC) THERAPY, INTENSITY-MODULATED RADIOTHERAPY, AND 3D CONFORMAL RADIOTHERAPY FOR PRIMARY LIVER TUMOURS Jacob John a,*, Roshni Sivasevan a, Arun Sankar Sudha a, Choondal Devan Sivanandan a, Sajeed Abdurahman a, Raghukumar Paramu b, Shaiju Vasudevan Sreedevi b, Preethi Sara George c, Puthuveettil Govindan Jayaprakash a. a Division of Radiation Oncology, Regional Cancer Centre, Thiruvananthapuram, India, b Division of Radiation Physics, Regional Cancer Centre, Thiruvananthapuram, India, c Division of Epidemiology and Biostatistics, Regional Cancer Centre, Thiruvananthapuram, India Background: To compare the dosimetric outcomes of volumetric arc radiotherapy (RapidArc), intensity-modulated radiotherapy (IMRT), and 3D conformal radiotherapy (3DCRT) plans for primary liver tumours. Methods: 7 patients with localised unresectable hepatocellular carcinoma were included in this study. CT simulation was done with voluntary deep inspiratory breath-holding after administering 80–90 mL of intravenous iodinated contrast. The mean tumour size was 5.6 cm (range 2.1–9.8) and two patients had multiple lesions (range 1–3). All patients were planned for partial liver irradiation for a total dose of 50–66 Gy in 2 Gy per fraction with conformal techniques. 3DCRT, IMRT, and RapidArc plans were generated using Eclipse planning system v.13 and dosimetric analysis was done to evaluate the plan quality and efficiency, including CI, HI, MU delivered, PTV Dmean and Dmax. IMRT plans had 3–5 fields and RapidArc plans had 3–5 arcs. V10,V20,V30 and V40 of normal liver and Dmean of organs at risk (OAR) and Dmax of spinal cord were also evaluated. Analysis was done using ANOVA and paired t-test with two tailed p < 0.05. Findings: All the three techniques had comparable PTV coverage, dose homogeneity, and OAR sparing. IMRT and Rapid Arc had a significantly better conformity index than 3DCRT (p = 0.03). The high dose areas within the normal liver; V40 and V30 were significantly lower in RapidArc and IMRT plans (p = 0.03 and p = 0.04, respectively), although no significant differences were noted between IMRT and RapidArc. One patient could not attain the normal liver constraint V33 <33 Gy, which was attained with both IMRT and RapidArc plans. Interpretation: RapidArc and IMRT provide better normal liver sparing and conformity than 3DCRT. However, RapidArc was not better than IMRT for liver protection. Further large trials are required to clearly establish the benefits of IMRT and Rapid Arc techniques to treat primary liver tumours.
http://dx.doi.org/10.1016/j.ejca.2015.06.099
P0180 EFFECT OF PIOGLITAZONE ON PROLIFERATION AND APOPTOSIS IN HUMAN UTERINE LEIOMYOSARCOMA CELLS Yi Zhao a,*, Katja Lucht b, Maaz Zuhayra a, Ingolf Cascorbi b, Ulf a Lu¨tzen a, Juraj Culman b. Department of Nuclear Medicine, Molecular Imaging, Diagnostics and Therapy, University Hospital of Schleswig-Holstein, Kiel, Germany, b Institute of Experimental and Clinical Pharmacology, University Hospital of Schleswig-Holstein, Kiel, Germany Background: SK-UT-1 cells, a human uterine leiomyosarcoma cell line, and human uterine smooth muscle cells (HutSMC) (controls) express the peroxisome proliferator-activated receptor c (PPARc). We investigated the effects of the PPARc agonist pioglitazone on the proliferation and induction of apoptosis in SK-UT-1 cells and HutSMC. Methods: Cells were exposed to pioglitazone (10 or 25 lmol/l) in the presence or absence of the selective PPARc antagonist, GW 9226 (1 lmol/l). Cell proliferation was evaluated by WST-1 assay and cresyl violet staining. Western blot analysis was used to quantify the cleaved caspase-3, Bax, and Bad proteins. Cellular toxicity of pioglitazone was assessed by lactate dehydrogenase (LDH) release. Findings: Pioglitazone increased the expression of the PPARc in SK-UT-1 cells and in HutSMC by a PPARc-dependent mechanism. Pioglitazone reduced cell proliferation in both quiescent and proliferating SK-UT-1 cells in concentration and time dependent fashion. These effects were partially mediated by PPARc. In SK-UT-1 cells, pioglitazone (25 lmol/l) activated caspase-3 and induced Bad, Bax, and p53 proteins. Higher levels of MEK and ERK and p-MEK and p-ERK were detected in quiescent SK-UT-1 cells than in quiescent HutSMC. Pioglitazone reduced p-ERK and p-MEK in SK-UT-1 cells in a time dependent manner, but did not alter p-MEK/MEK and p-ERK/ERK levels in HutSMC. Pioglitazone did not exert any cytotoxic effects in SK-UT-1 or HutSMC. Interpretation: We demonstrate that pioglitazone reduces proliferation and promotes apoptosis in quiescent and proliferating leiomyosarcoma cells.
http://dx.doi.org/10.1016/j.ejca.2015.06.100
P0184 ESTABLISHMENT OF A CELL MICROENCAPSULATION MODEL USING MUCOEPIDERMOID CARCINOMA CELLS Li-juan Guo a, Xiong-fei Pan b, Sen Yang c,*, Wings Ty Loo d,e, Louis W C Chow d, William Tsang e. a Medical Beauty Department, Suining Central Hospital, Suining, China, b Department of Epidemiology, West China School of Public Health, Sichuan University, Chengdu, China, c Department of Stomatology, Suining Central Hospital, Suining, China, d UNIMED Medical Institute and Organisation for Oncology and Translational Research, Hong Kong, e Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hong Kong Background: Adherent cell culturing is a mature cell culturing technique mainly used for research on molecular mechanism of biological function of adherent cells. Specifically, it is widely applied in studies of cancer onset and development, and of the action of pharmaceutical
Abstracts / 51 (2015) e1–e36
agents on cancer cells. Cell microencapsulation is a technique by which cells are encapsulated in a semi-permeable microcapsule and live like those in physiological conditions with normal nutritional supply. It is a culturing technique that ranks between monolayer and three-dimensional culture. With microencapsulation, adherent cells grow in a three dimensional manner, and its metabolism and genetic expression also change, similar to solid tumours. Methods: We aimed to establish a cell microencapsulation model using human mucoepidermoid carcinoma cells (MCCs), and assess the cell culture model based on cell growth characteristics, proliferation activity, and protein expression. After MCCs had been isolated and cultured in RPMI-1640 medium, cell growth characteristics, proliferation activity, and protein expression of microencapsulated MCCs and conventional adherent MCCs (as control) were compared. Findings: Results showed MCCs in microcapsules grew in blocks with favourable proliferation activity. On day 3, the cell count in the microencapsulation group was significantly higher than the control group (t = 0.480, p < 0.05). On day 7, cell proliferation had not reached a plateau or declined. Compared with adherent MCCs, microencapsulated MCCs showed significantly higher expression of vascular endothelial growth factor (VEGF) and bFGF (t = 7.617, p < 0.01; t = 6.011, p < 0.01), while TSP-1 was significantly less expressed (t = 12.45, p < 0.001). Interpretation: Microencapsulation culture may help to establish three-dimensional growth of tumour cells in vitro that promote protein expression for angiogenesis. It may be a promising model for functional research of tumour-related genes. In addition, it may be used in studies on biological characteristics of tumour cells and screening of antitumour pharmaceuticals. It will also have prospect in the in situ amplification of stem cells due to convenient inoculation and collection.
http://dx.doi.org/10.1016/j.ejca.2015.06.101
P0191 HISTOGRAM ANALYSIS OF APPARENT DIFFUSION COEFFICIENTS AFTER NEOADJUVANT CHEMOTHERAPY IN BREAST CANCER S.H. Kim *, Y.J. Kim. The Catholic University of Korea, Republic of Korea Background: The purpose of our study was to evaluate change of the apparent diffusion coefficient (ADC) histogram during the neoadjuvant chemotherapy (NAC) in breast cancer, and to compare changes between pathologically verified responders and non-responders. Methods: 62 patients received NAC followed by surgery. We defined responders and non-responders based on 30% reduction in tumour cells using the Miller-Payne Grading System. All patients underwent 3T magnetic resonance (MR) with diffusion-weighted imaging (DWI) before the NAC and after the completion of two cycles of NAC. ADC histogram analysis encompassing the entire tumour was performed and various ADC parameters (mean, minimum, 10th, 25th, 50th, 75th, 90th percentile, maximum ADCs, skewness, and kurtosis) were obtained. Findings: Mean, minimum, 10th, 25th, 50th, and 75th percentile ADCs significantly increased after NAC (p = 0.0129, p = 0.0004, p = 0.0047, p = 0.0002, p = 0.0006, p = 0.0030) and maximum ADC significantly decreased (p = 0.0003). Skewness changed into less positive (p < 0.0001) and kurtosis decreased (p = 0.0168) after NAC. Although there was no statistical significance, mean, minimum, 10th,
e35
25th, 50th, 75th, and 90th percentile ADCs tended to decrease more in responders compared with non-responders. Interpretation: There is significant change in distribution of ADC after NAC. ADC histogram analysis quantitatively demonstrates the alterations more precisely during the treatment course. http://dx.doi.org/10.1016/j.ejca.2015.06.102
P0192 SENTINEL NODE BIOPSY IN BREAST CANCER USING ONLY METHYLENE BLUE DYE: A PROSPECTIVE STUDY IN A RURAL TERTIARY CARE CENTRE R. Shah *, S. Virani, S. Shah. Kailash Cancer Hospital and Research Centre, Vadodara, India Background: Breast carcinoma is the most common malignancy in women and is the leading cause of death in their middle age. Sentinel lymph node biopsy (SLNB) is a reliable and minimally invasive diagnostic method to determine the regional nodal status in breast cancer and provides accurate staging, such that axillary lymph node dissection can be avoided in negative sentinel node patients. The aim of this study was to assess SLNB, using methylene blue dye, and its accuracy. The complications of using methylene blue dye were also studied. Methods: 138 patients with breast cancer were subjected to SLNB (using methylene blue dye) followed by complete axillary lymph node dissection. The lymph nodes with positive dye were identified. The dye was injected 30 min prior to surgery and the stained lymph nodes were identified during dissection. The haemodynamics of the patients was assessed during and after the procedure. Patients were followed up in the post-operative period, and for the final histopathology report, complications such as wound healing and urine discolouration were assessed. Findings: Of 138 patients with dye injected, 124 (89.85%) patients showed stained lymph nodes. Of 124 patients with positive stain, 67 (54.03%) patients showed evidence of malignancy. Of 67 patients with malignancy-positive lymph nodes, 18 patients had positive sentinel node only. In 49 patients, both sentinel and one or more axillary nodes were positive, whereas in 53 patients both nodal statuses were negative. Four patients had negative sentinel node and positive axillary node. All 14 patients in whom sentinel node could not be identified were negative for cancer in axillary nodes. Seven patients had minor dye-related complications. Interpretation: SLNB with methylene blue dye alone can be considered in breast carcinoma as a reliable, accurate, cost effective, and safe method to detect lymph node status. http://dx.doi.org/10.1016/j.ejca.2015.06.103
P0193 MARSDENIA TENACISSIMA EXTRACT ENHANCES GEFITINIB EFFICACY IN NON-SMALL-CELL LUNG CANCER XENOGRAFTS Shu-Yan Han a,b, Wei Zhao a,c, Hong Sun a,b, Ning Zhou a,b, Fei a Zhou a,b, Guo An a,d, Ping-Ping Li a,b. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China,