| 1. |
- Lee, Ji Soo, et al.
(author)
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Genetic Association and Expression Analyses of the Phosphatidylinositol-4-Phosphate 5-Kinase (PIP5K1C) Gene in Alcohol Use DisorderRelevance for Pain Signaling and Alcohol Use
- 2018
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In: Alcoholism. - : WILEY. - 0145-6008 .- 1530-0277. ; 42:6, s. 1034-1043
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Journal article (peer-reviewed)abstract
- BackgroundThe gene encoding phosphatidylinositol-4-phosphate 5-kinase (PIP5K1C) has been recently implicated in pain regulation. Interestingly, a recent cross-tissue and cross-phenotypic epigenetic analysis identified the same gene in alcohol use disorder (AUD). Given the high comorbidity between AUD and chronic pain, we hypothesized that genetic variation in PIP5K1C might contribute to susceptibility to AUD. MethodsWe conducted a case-control association study of genetic variants in PIP5K1C. Association analyses of 16 common PIP5K1C single nucleotide polymorphisms (SNPs) were conducted in cases and controls of African (427 cases and 137 controls) and European ancestry (488 cases and 324 controls) using standard methods. In addition, given the prominent role of the opioid system in pain signaling, we investigated the effects of acute alcohol exposure on PIP5K1C expression in humanized transgenic mice for the -opioid receptor that included the OPRM1 A118G polymorphism, a widely used mouse model to study analgesic response to opioids in pain. PIP5K1C expression was measured in the thalamus and basolateral amygdala (BLA) in mice after short-term administration (single 2g/kg dose) of alcohol or saline using immunohistochemistry and analyzed by 2-way analysis of variance. ResultsIn the case-control association study using an NIAAA discovery sample, 8 SNPs in PIP5K1C were significantly associated with AUD in the African ancestry (AA) group (pamp;lt;0.05 after correction; rs4807493, rs10405681, rs2074957, rs10432303, rs8109485, rs1476592, rs10419980, and rs4432372). However, a replication analysis using an independent sample (N=3,801) found no significant associations after correction for multiple testing. In the humanized transgenic mouse model with the OPRM1 polymorphism, PIP5K1C expression was significantly different between alcohol and saline-treated mice, regardless of genotype, in both the thalamus (pamp;lt;0.05) and BLA (pamp;lt;0.01). ConclusionsOur discovery sample shows that genetic variants in PIP5K1C are associated with AUD in the AA group, and acute alcohol exposure leads to up-regulation of PIP5K1C, potentially explaining a mechanism underlying the increased risk for chronic pain conditions in individuals with AUD.
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| 2. |
- Lee, Yeh Chen, et al.
(author)
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Symptom burden and quality of life with chemotherapy for recurrent ovarian cancer : the Gynecologic Cancer InterGroup-Symptom Benefit Study
- 2022
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In: International Journal of Gynecological Cancer. - : BMJ Publishing Group. - 1048-891X .- 1525-1438. ; 32:6, s. 761-768
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Journal article (peer-reviewed)abstract
- Objective The Gynecologic Cancer InterGroup (GCIG)-Symptom Benefit Study was designed to evaluate the effects of chemotherapy on symptoms and health-related quality of life (HRQL) in women having chemotherapy for platinum resistant/refractory recurrent ovarian cancer (PRR-ROC) and potentially platinum sensitive with >= 3 lines of chemotherapy (PPS-ROC >= 3). Methods Participants completed the Measure of Ovarian Cancer Symptoms and Treatment (MOST) and European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire QLQ-C30 questionnaires at baseline and every 3-4 weeks until progression. Participants were classified symptomatic if they rated >= 4 of 10 in at least one-third of symptoms in the MOST index. Improvement in MOST was defined as two consecutive scores of <= 3 in at least half of the symptomatic items at baseline. Improvement in HRQL was defined as two consecutive scores >= 10 points above baseline in the QLQ-C30 summary score scale (range 0-100). Results Of 948 participants enrolled, 910 (96%) completed baseline questionnaires: 546 with PRR-ROC and 364 with PPS-ROC >= 3. The proportions of participants symptomatic at baseline as per MOST indexes were: abdominal 54%, psychological 53%, and disease- or treatment-related 35%. Improvement was reported in MOST indexes: abdominal 40%, psychological 35%, and disease- or treatment-related 38%. Median time to improvement in abdominal symptoms occurred earlier for PRR-ROC than for PPS-ROC >= 3 (4 vs 6 weeks, p=0.044); median duration of improvement was also similar (9.0 vs 11.7 weeks, p=0.65). Progression-free survival was longer among those with improvement in abdominal symptoms than in those without (median 7.2 vs 2.5 months, p<0.0001). Improvements in HRQL were reported by 77/448 (17%) with PRR-ROC and 61/301 (20%) with PPS-ROC >= 3 (p=0.29), and 102/481 (21%) of those with abdominal symptoms at baseline. Conclusion Over 50% of participants reported abdominal and psychological symptoms at baseline. Of those, 40% reported an improvement within 2 months of starting chemotherapy. Approximately one in six participants reported an improvement in HRQL. Symptom monitoring and supportive care is important as chemotherapy palliated less than half of symptomatic participants.
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| 3. |
- Campbell, Rachel, et al.
(author)
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Measure of Ovarian Symptoms and Treatment concerns (MOST) indexes and their associations with health-related quality of life in recurrent ovarian cancer
- 2022
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In: Gynecologic Oncology. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 0090-8258 .- 1095-6859. ; 166:2, s. 254-262
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Journal article (peer-reviewed)abstract
- Purpose. The Measure of Ovarian Symptoms and Treatment (MOST) concerns is a validated patient-reported symptom assessment tool for assessing symptom benefit and adverse effects of palliative chemotherapy in women with recurrent ovarian cancer (ROC). We aimed to examine (i) how symptoms within MOST symptom indexes track together (i.e. co-occur) and (ii) the association between MOST symptom indexes and key aspects of health-related quality of life (HRQL). Method. A prospective cohort of women with ROC completed the MOST-T35, EORTC QLQ-C30 and EORTC QLQ-OV28 at baseline and before each cycle of chemotherapy. Analyses were conducted on baseline and end -of-treatment data. Exploratory factor analysis and hierarchical cluster analysis identified groups of co-occurring symptoms. Path models examined associations between MOST symptom indexes and HRQL. Results. Data from 762 women at baseline and 681 at treatment-end who completed all 22 symptom-specific MOST items and at least one HRQL measure were analysed. Four symptom clusters emerged at baseline and treatment-end: abdominal symptoms, symptoms associated with peripheral neuropathy, nausea and vomiting, and psychological symptoms. Psychological symptoms (MOST-Psych) and symptoms due to disease (ovarian cancer) or treatment (MOST-DorT) were associated with poorer scores on QLQ-C30 and OV28 functioning do-mains and worse overall health at both time points. Conclusion. Four MOST symptom clusters were consistent across statistical methods and time points. These findings suggest that routine standardized assessment of psychological and physical symptoms in clinical prac-tice with MOST plus appropriate symptom management referral pathways is an intervention for improving HRQL that warrants further research. (c) 2022 Elsevier Inc. All rights reserved.
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| 4. |
- Roncolato, Felicia, et al.
(author)
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Hidden in plain sight - Survival consequences of baseline symptom burden in women with recurrent ovarian cancer
- 2024
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In: Gynecologic Oncology. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 0090-8258 .- 1095-6859. ; 185, s. 128-137
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Journal article (peer-reviewed)abstract
- Objective. To describe the baseline symptom burden(SB) experienced by patients(pts) with recurrent ovarian cancer(ROC) prior and associations with progression free survival (PFS) and overall survival (OS). Methods. We analysed baseline SB reported by pts. with platinum resistant/refractory ROC (PRR-ROC) or potentially-platinum sensitive ROC receiving their third or greater line of chemotherapy (PPS-ROC >= 3) enrolled in the Gynecologic Cancer InterGroup - Symptom Benefit Study (GCIG-SBS) using the Measure of Ovarian Symptoms and Treatment concerns (MOST). The severity of baseline symptoms was correlated with PFS and OS. Results. The 948 pts. reported substantial baseline SB. Almost 80% reported mild to severe pain, and 75% abdominal symptoms. Shortness of breath was reported by 60% and 90% reported fatigue. About 50% reported moderate to severe anxiety, and 35% moderate to severe depression. Most (89%) reported 1 or more symptoms as moderate or severe, 59% scored 6 or more symptoms moderate or severe, and 46% scored 9 or more symptoms as moderate or severe. Higher SB was associated with significantly shortened PFS and OS; five symptoms had OS hazard ratios larger than 2 for both moderate and severe symptom cut-offs (trouble eating, vomiting, indigestion, loss of appetite, and nausea; p < 0.001). Conclusion. Pts with ROC reported high SB prior to starting palliative chemotherapy, similar among PRR-ROC and PPS-ROC >= 3. High SB was strongly associated with early progression and death. SB should be actively managed and used to stratify patients in clinical trials. Clinical trials should measure and report symptom burden and the impact of treatment on symptom control. (c) 2024 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://
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