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Abstract 15: Cancer-related fatigue in gynecologic oncology patients undergoing chemotherapy
Abstracts / Gynecologic Oncology 137 (2015) 591–599
doi:10.1016/j.ygyno.2015.03.030
Abstract 14: Glutamine supports ovarian cancer cell proliferation through modulation of the mTOR/S6 pathway D.R. Roque, L. Yuan, W.Z. Wysham, C. Zhou, V. Bae-Jump. University of North Carolina, Chapel Hill, Division of Gynecologic Oncology, NC, United States Objectives: Cancer cells have unique metabolism characteristics to meet the elevated energetic and biosynthetic demands of rapid cell growth and proliferation. Glutamine is one of the main nutrients used by tumor cells for biosynthesis. In addition, glutamine promotes cell glycolysis and functions as a cell-signaling regulator. Therefore, an understanding of the effects of glutamine on cell growth in ovarian cancer cells would allow us to develop appropriate anti-metabolic strategies. We aimed to investigate the underlying mechanism of action of glutamine in ovarian cancer cells as well as its effects on cell proliferation.
Results: Patient-reported fatigue was significantly associated with interpersonal support (P = 0.05) and age (P = 0.01) but not significantly associated with amount of exercise, hemoglobin level, ethnicity or servings of vegetables consumed daily. Ovarian, cervical, vulvar, and vaginal cancer patients reported significantly more fatigue than patients with uterine cancers. Current employment was not associated with fatigue. While fatigue trended towards decreasing with time since chemotherapy, it did not reach significance and patients continued to report significant fatigue over a year after chemotherapy. Conclusions: Cancer related fatigue is a ubiquitous complaint in gynecologic oncology patients undergoing chemotherapy, especially in patients with less perceived interpersonal support and advancing age. doi:10.1016/j.ygyno.2015.03.032
DP
Methods: Three ovarian cancer cell lines, HEY, SKOV3, and IGROV1, were assayed for glutamine dependence. Cell proliferation was assessed by MTT assay after exposure to different concentrations of glutamine. Cell cycle progression and apoptosis were evaluated by Cellometer. Western blot analysis was performed to evaluate the effects of glutamine on the protein expression in cell cycle, cell stress, glycolysis, glutaminase, and mTOR/p-S6 pathways. Glucose uptake, lactate level, ATP production, reactive oxygen species (ROS) assay and glutamate dehydrogenase (GDH) activity of cells were assessed by ELISA assay.
Methods: Fifty English and Spanish speaking patients with a gynecologic malignancy undergoing chemotherapy were administered a survey which collected self-defined ethnicity, zip code, language spoken at home, employment, and current diet and exercise characteristics. The surveys included the FACIT-F questionnaire and the ISEL-12 measure of perceived interpersonal support. Patient charts were also reviewed to abstract the type of malignancy, status of treatment, current hemoglobin level, BMI, and age. These data were de-identified and entered into a database for analysis. Analysis was performed using a logistic regression for continuous variables and a student t test for discrete variables.
OF
radiation improve survival in our model, there was not a significant improvement in survival over time.
RO
596
TE
Results: Glutamine promoted optimal cell proliferation under normal growth media in a dose dependent manner in the three ovarian cancer cell lines, glutamine starvation induced cell apoptosis and cell cycle G1 arrest. Depletion of Glutamine reduced cell glucose uptake, cell lactate level, and ATP production. It also induced ROS production and stress protein expression. Glutamine activated GDH by modulating the mTOR/ p-S6 pathway. Knockdown of S6 by siRNA transfection inhibited GDH activity and reduced cell proliferation induced by glutamine.
Abstract 16: Multimodal pain control is associated with reduced hospital stay following open abdominal hysterectomy M. Ulm, J. Santoso, B. Jennings, J. Wan. University of Tennessee Health Sciences Center, Memphis, TN, United States Objectives: The aim of this research was to study the effectiveness of multimodal pain protocol (MMPC) in reducing hospital stay after open abdominal hysterectomy.
EC
Methods: The study design was a comparison of a prospective cohort with a retrospective historical control. We enrolled endometrial cancer patients undergoing open abdominal hysterectomy with lymphadenectomy. Control patients from 2008 to 2010 who received morphine PCA alone were compared with a similar demographic group of patients from 2011 to 2013 who received MMPC. MMPC consisted of gabapentin (900 mg PO) and acetaminophen (1 g IV) administered 45–60 min preoperatively. The surgical site was injected with bupivacaine with 0.5% epinephrine prior to incision. The postoperative pain control regimen consisted of gabapentin (300 mg PO every 8 h), acetaminophen (1 g IV every 8 h for 24 h postoperatively), ketorolac (15 mg IV every 6 h for 48 h postoperatively), morphine PCA (2 mg IV every 10 min, no basal rate, for the first night postoperatively) and oxycodone/acetaminophen (10/ 325 mg PO every 6 h as needed).
CO
RR
Conclusions: Glucose and glutamine are major sources of energy production and survival in ovarian cancer cells. Glutamine complemented ATP production by affecting glycolysis and the tricarboxylic acid cycle. The mTOR/S6 pathway controlled glutamine metabolism by regulating the activity of GDH and glutaminase. Inhibition of glutamine metabolism reduced ovarian cancer cell growth. Thus, targeting glutamine metabolism might be helpful in the treatment of ovarian cancer.
doi:10.1016/j.ygyno.2015.03.031
UN
Abstract 15: Cancer-related fatigue in gynecologic oncology patients undergoing chemotherapy K. Shieldsa, C. Craigb, L. Baxterb, L. Rendab, J. Pipeb, B. Monkc, D. Chasec. aPhoenix Integrated Residency in Obstetrics and Gynecology, Phoenix, AZ, United States, bDignity Health St. Joseph's Hospital and Medical Center, Phoenix, AZ, United States, cUniversity of Arizona Cancer Center at Dignity Health St. Joseph's Hospital and Medical Center Division of Gynecologic Oncology, Phoenix, AZ, United States Objectives: Cancer-related fatigue is the most commonly reported side effect of cancer therapy. The aim of this study is to identify characteristics of patients with cancer related fatigue in a population of gynecologic oncology patients undergoing chemotherapy.
Results: The length of hospital stay (LOH) of the study cohort (N = 105 with MMPC) was compared with the historical control undergoing similar procedures by the same surgeon with postoperative morphine alone (N = 113 without MMPC). There were no differences in demographic, uterine cancer stage, or comorbidities between the two arms. The LOH was 1.6 days for patients receiving MMPC and 3.3 days for patients who received morphine alone (P b 0.001). One patient was readmitted for postoperative pain from the MMPC group. Conclusions: Multimodal pain control is associated with significantly reduced hospital stay after open abdominal hysterectomy. doi:10.1016/j.ygyno.2015.03.033
doi:10.1016/j.ygyno.2015.03.030
Abstract 14: Glutamine supports ovarian cancer cell proliferation through modulation of the mTOR/S6 pathway D.R. Roque, L. Yuan, W.Z. Wysham, C. Zhou, V. Bae-Jump. University of North Carolina, Chapel Hill, Division of Gynecologic Oncology, NC, United States Objectives: Cancer cells have unique metabolism characteristics to meet the elevated energetic and biosynthetic demands of rapid cell growth and proliferation. Glutamine is one of the main nutrients used by tumor cells for biosynthesis. In addition, glutamine promotes cell glycolysis and functions as a cell-signaling regulator. Therefore, an understanding of the effects of glutamine on cell growth in ovarian cancer cells would allow us to develop appropriate anti-metabolic strategies. We aimed to investigate the underlying mechanism of action of glutamine in ovarian cancer cells as well as its effects on cell proliferation.
Results: Patient-reported fatigue was significantly associated with interpersonal support (P = 0.05) and age (P = 0.01) but not significantly associated with amount of exercise, hemoglobin level, ethnicity or servings of vegetables consumed daily. Ovarian, cervical, vulvar, and vaginal cancer patients reported significantly more fatigue than patients with uterine cancers. Current employment was not associated with fatigue. While fatigue trended towards decreasing with time since chemotherapy, it did not reach significance and patients continued to report significant fatigue over a year after chemotherapy. Conclusions: Cancer related fatigue is a ubiquitous complaint in gynecologic oncology patients undergoing chemotherapy, especially in patients with less perceived interpersonal support and advancing age. doi:10.1016/j.ygyno.2015.03.032
DP
Methods: Three ovarian cancer cell lines, HEY, SKOV3, and IGROV1, were assayed for glutamine dependence. Cell proliferation was assessed by MTT assay after exposure to different concentrations of glutamine. Cell cycle progression and apoptosis were evaluated by Cellometer. Western blot analysis was performed to evaluate the effects of glutamine on the protein expression in cell cycle, cell stress, glycolysis, glutaminase, and mTOR/p-S6 pathways. Glucose uptake, lactate level, ATP production, reactive oxygen species (ROS) assay and glutamate dehydrogenase (GDH) activity of cells were assessed by ELISA assay.
Methods: Fifty English and Spanish speaking patients with a gynecologic malignancy undergoing chemotherapy were administered a survey which collected self-defined ethnicity, zip code, language spoken at home, employment, and current diet and exercise characteristics. The surveys included the FACIT-F questionnaire and the ISEL-12 measure of perceived interpersonal support. Patient charts were also reviewed to abstract the type of malignancy, status of treatment, current hemoglobin level, BMI, and age. These data were de-identified and entered into a database for analysis. Analysis was performed using a logistic regression for continuous variables and a student t test for discrete variables.
OF
radiation improve survival in our model, there was not a significant improvement in survival over time.
RO
596
TE
Results: Glutamine promoted optimal cell proliferation under normal growth media in a dose dependent manner in the three ovarian cancer cell lines, glutamine starvation induced cell apoptosis and cell cycle G1 arrest. Depletion of Glutamine reduced cell glucose uptake, cell lactate level, and ATP production. It also induced ROS production and stress protein expression. Glutamine activated GDH by modulating the mTOR/ p-S6 pathway. Knockdown of S6 by siRNA transfection inhibited GDH activity and reduced cell proliferation induced by glutamine.
Abstract 16: Multimodal pain control is associated with reduced hospital stay following open abdominal hysterectomy M. Ulm, J. Santoso, B. Jennings, J. Wan. University of Tennessee Health Sciences Center, Memphis, TN, United States Objectives: The aim of this research was to study the effectiveness of multimodal pain protocol (MMPC) in reducing hospital stay after open abdominal hysterectomy.
EC
Methods: The study design was a comparison of a prospective cohort with a retrospective historical control. We enrolled endometrial cancer patients undergoing open abdominal hysterectomy with lymphadenectomy. Control patients from 2008 to 2010 who received morphine PCA alone were compared with a similar demographic group of patients from 2011 to 2013 who received MMPC. MMPC consisted of gabapentin (900 mg PO) and acetaminophen (1 g IV) administered 45–60 min preoperatively. The surgical site was injected with bupivacaine with 0.5% epinephrine prior to incision. The postoperative pain control regimen consisted of gabapentin (300 mg PO every 8 h), acetaminophen (1 g IV every 8 h for 24 h postoperatively), ketorolac (15 mg IV every 6 h for 48 h postoperatively), morphine PCA (2 mg IV every 10 min, no basal rate, for the first night postoperatively) and oxycodone/acetaminophen (10/ 325 mg PO every 6 h as needed).
CO
RR
Conclusions: Glucose and glutamine are major sources of energy production and survival in ovarian cancer cells. Glutamine complemented ATP production by affecting glycolysis and the tricarboxylic acid cycle. The mTOR/S6 pathway controlled glutamine metabolism by regulating the activity of GDH and glutaminase. Inhibition of glutamine metabolism reduced ovarian cancer cell growth. Thus, targeting glutamine metabolism might be helpful in the treatment of ovarian cancer.
doi:10.1016/j.ygyno.2015.03.031
UN
Abstract 15: Cancer-related fatigue in gynecologic oncology patients undergoing chemotherapy K. Shieldsa, C. Craigb, L. Baxterb, L. Rendab, J. Pipeb, B. Monkc, D. Chasec. aPhoenix Integrated Residency in Obstetrics and Gynecology, Phoenix, AZ, United States, bDignity Health St. Joseph's Hospital and Medical Center, Phoenix, AZ, United States, cUniversity of Arizona Cancer Center at Dignity Health St. Joseph's Hospital and Medical Center Division of Gynecologic Oncology, Phoenix, AZ, United States Objectives: Cancer-related fatigue is the most commonly reported side effect of cancer therapy. The aim of this study is to identify characteristics of patients with cancer related fatigue in a population of gynecologic oncology patients undergoing chemotherapy.
Results: The length of hospital stay (LOH) of the study cohort (N = 105 with MMPC) was compared with the historical control undergoing similar procedures by the same surgeon with postoperative morphine alone (N = 113 without MMPC). There were no differences in demographic, uterine cancer stage, or comorbidities between the two arms. The LOH was 1.6 days for patients receiving MMPC and 3.3 days for patients who received morphine alone (P b 0.001). One patient was readmitted for postoperative pain from the MMPC group. Conclusions: Multimodal pain control is associated with significantly reduced hospital stay after open abdominal hysterectomy. doi:10.1016/j.ygyno.2015.03.033