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Deep learning has been successful at predicting epigenomic profiles from DNA sequences. Most approaches frame this task as a binary classification relying on peak callers to define functional activity. Recently, quantitative models have emerged to directly predict the experimental coverage values as a regression. As new models continue to emerge with different architectures and training configurations, a major bottleneck is forming due to the lack of ability to fairly assess the novelty of proposed models and their utility for downstream biological discovery. Here we introduce a unified evaluation framework and use it to compare various binary and quantitative models trained to predict chromatin accessibility data. We highlight various modeling choices that affect generalization performance, including a downstream application of predicting variant effects. In addition, we introduce a robustness metric that can be used to enhance model selection and improve variant effect predictions. Our empirical study largely supports that quantitative modeling of epigenomic profiles leads to better generalizability and interpretability.

Highly sensitive detection of chemokines in various biological matrices and its interaction with a natural receptor molecule has tremendous importance in cell signaling, medical diagnostics, and therapeutics. In this direction, we have designed the first bifunctional nanobiosensor for chemokine screening and detection in a single experimental setting. The sensor probe was fabricated by immobilizing CXCR2 on the gold nanoparticles (AuNPs) deposited 2,2':5',2''-terthiophene-3' (p-benzoic acid) (TBA) nanocomposite film. The interaction between CXCR2 and chemokines was studied using electrochemical impedance spectroscopy (EIS) and voltammetry. CXCL5 among three ligands showed the strongest affinity to CXCR2, which was further utilized to develop an amperometric CXCL5 biosensor. Analytical parameters, such as CXCR2 receptor concentration, temperature, pH, and incubation time were optimized to obtain the high sensitivity. A dynamic range for CXCL5 detection was obtained between 0.1 and 10ng/mL with the detection limit of 0.078 ± 0.004ng/mL (RSD < 4.7%). The proposed biosensor was successfully applied to detect CXCL5 in clinically relevant concentrations in human serum and colorectal cancer cells samples with high sensitivity and selectivity. Interference effect and the stability of the developed biosensor were also evaluated. Method verification was performed by comparing the results using commercially available ELISA kit for CXCL5 detection.

The aberrant constitutive activation of the transcription factor, cyclic-AMP response element- binding (CREB) protein, has been associated with poor prognosis and chemotherapeutic resistance in KRAS-mutated human cancers, one of which includes non-small cell lung cancer (NSCLC). However, the role of CREB in KRAS-driven lung tumorigenesis has not been fully understood. Using adenoviral delivery of Cre specifically to the mouse lung, we generated a new transgenic lung cancer mouse model driven by Kras activating mutation G12D and concomitant with Creb loss (KrasLSL-G12D/+; CrebFlox/Flox). In this study, we used this model to show that a proto-oncogenic transcription factor CREB, is required for KRAS-driven lung tumorigenesis. Loss of Creb (Creb-/-) in the mice harboring Kras-mutated lung tumors significantly suppressed tumor development, and thus, dramatically prolonged mouse survival when compared to either wild (Creb+/+) or heterozygous (Creb+/-) deletion of Creb. Mechanistically, we identified a few novel CREB target gene. These data suggest that CREB is essential for KRAS-driven lung tumorigenesis and that CREB could be a potential target for therapeutic treatment for individuals suffering from KRAS-mutant lung cancers. Citation Format: Jong woo Lee, Frank J. Slack, Eric J. Nestler, Roy S. Herbst, Jaseok Peter Koo. CREB is required for KRAS-driven lung tumorigenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3334.

Previously, we demonstrated, in a randomized clinical trial, the effectiveness of a psychoeducational intervention to decrease pain intensity scores and increase patients' knowledge of cancer pain management with a sample of oncology patients with pain from bone metastasis. In the present study, we evaluated for changes in mood states (measured using the Profile of Mood States), quality of life (QOL; measured using the Medical Outcomes Study Short Form-36 (SF-36)), and pain's level of interference with function (measured using the Brief Pain Inventory (BPI)) from baseline to the end of the intervention first between the intervention and the standard care groups and then within the intervention group based on the patients' level of response to the intervention (i.e., patients were classified as non-responders, partial responders, or responders). No differences were found in any of these outcome measures between patients in the standard care and intervention groups. However, when patients in the intervention group were categorized using a responder analysis approach, significant differences in the various outcome measures were found among the three respondent groups. Differences in the physical and mental component summary scores on the SF-36 and the interference items on the BPI, among the three respondent groups, were not only statistically significant but also clinically significant. The use of responder analysis in analgesic trials may help to identify unique subgroups of patients and lead to the development of more effective psychoeducational interventions.

Purpose. The efficacy and safety of fentanyl hydrochloride patient-controlled trans-dermal system (PCTS) for management of acute postoperative pain are discussed. Summary. Fentanyl hydrochloride PCTS is a self-contained, needle-free, credit-card-sized fentanyl-delivery system that is worn on the patient’s arm or chest. The system uses iontophoretic technology to actively deliver preprogrammed doses of fentanyl into the systemic circulation when activated by the patient on demand. PCTS is as safe and effective as i.v. morphine patient-controlled analgesia and superior to placebo for managing acute postoperative pain. Fentanyl absorption from PCTS is clinically insignificant when the device is not activated. This contrasts with the transdermal fentanyl patch, which delivers fentanyl continuously for 72 hours via passive absorption and is indicated only for use in the management of chronic pain. Conclusion. Fentanyl hydrochloride PCTS is a self-contained iontophoretic fentanyl-delivery system that provides patients control over pain management and consistent management of pain without analgesic peaks and troughs.

Qualitative research may be combined fruitfully with intervention studies, but few examples provide detailed methodological strategies for doing so. In this article, we describe the qualitative component of a randomized clinical trial (RCT) of the PRO-SELF© Pain Control Program, an intervention that provides individualized education, coaching, and support for cancer pain management. We conducted three qualitative analyses of verbatim transcripts of “real-time” audiotaped intervention sessions. As a result, we were better able to ascertain the nature of the individualized coaching component of the intervention, patient and family caregiver use of selected intervention tools, and reasons the intervention did not work for some patients. Study results were used to increase the specificity with which the coaching portion of the intervention is described in the intervention protocol. © 2005 Wiley Periodicals, Inc. Res Nurs Health 28: 268–280, 2005

While chronic pain is experienced by approximately 50-90% of patients with metastatic cancer, little is known about sex differences in chronic cancer pain. Therefore, the purposes of this study, in a sample of oncology outpatients (n=187) who were experiencing pain from bone metastasis, were: 1) to determine if there were sex differences in various pain characteristics, including pain intensity, and 2) to determine if there were sex differences in the prescription and consumption of analgesic medications. No significant sex differences were found in any of the baseline pain characteristics. In addition, no significant sex differences were found in analgesic prescriptions or intake of analgesic medications. Of note, men reported significantly higher pain interference scores for sexual activity than women. The study findings are important because they suggest that, unlike in acute pain, sex may not influence patients' perceptions of and responses to chronic cancer pain.

Purpose This randomized clinical trial tested the effectiveness of the PRO-SELF Pain Control Program compared with standard care in decreasing pain intensity scores, increasing appropriate analgesic prescriptions, and increasing analgesic intake in oncology outpatients with pain from bone metastasis. Patients and Methods Patients were randomly assigned to the PRO-SELF intervention (n = 93) or standard care (n = 81). Patients in the standard care arm were seen by a research nurse three times and were called three times by phone between the home visits. PRO-SELF group patients were seen by specially trained intervention nurses and received a psychoeducational intervention, were taught how to use a pillbox, and were given written instructions on how to communicate with their physician about unrelieved pain and the need for changes in their analgesic prescriptions. Patients were coached during two follow-up home visits and three phone calls on how to improve their cancer pain management. Results Pain intensity scores decreased significantly from baseline (all P < .0001) in the PRO-SELF group (ie, least pain, 28.4%; average pain, 32.5%; and worst pain, 27.0%) compared with the standard care group (ie, least increased by 14.6%, average increased by 1.9%, and worst decreased by 1.2%). The percentage of patients in the PRO-SELF group with the most appropriate type of analgesic prescription increased significantly from 28.3% to 37.0% (P = .008) compared with a change from 29.6% to 32.5% in the standard care group. Conclusion The use of a psychoeducational intervention that incorporates nurse coaching within the framework of self-care can improve the management of cancer pain.

PURPOSE/OBJECTIVES: To describe the PRO-SELF(c): Pain Control Program, an educational approach that provides patients and family caregivers with the knowledge, skills, and nursing support needed to improve pain relief. DATA SOURCES: Published research studies, articles, and conference abstracts. DATA SYNTHESIS: Patients with cancer and family caregivers lack knowledge about pain management and side effects. Engaging in self-care behaviors improves patients' health outcomes. CONCLUSIONS: The PRO-SELF: Pain Control Program is an effective approach that can be used to help patients with cancer and their family caregivers obtain the knowledge and skills that are needed to manage pain. Three key strategies for delivering the PRO-SELF program are (a) provision of information using academic detailing, (b) skill building with ongoing nurse coaching, and (c) interactive nursing support. IMPLICATIONS FOR NURSING: Adequate pain relief is vital to decreasing cancer morbidity and improving patients' quality of life. The PRO-SELF: Pain Control Program should be implemented in all settings where cancer care takes place.

The purpose of this study was to describe the difficulties with pain management that patients and family caregivers bring to a nurse's attention during a teaching and coaching intervention. Data were obtained from audiotaped and transcribed interactions between intervention nurses and patients (n = 52) and their family caregivers (n = 33) who were participating in a randomized clinical trial of a nursing intervention called the PRO-SELF Copyright Pain Control Program. Using qualitative content analysis, we found that patients had difficulty in seven areas when they attempted to put a pain management regimen into practice, namely: obtaining the prescribed medication(s), accessing information, tailoring prescribed regimens to meet individual needs, managing side effects, cognitively processing information, managing new or unusual pain, and managing multiple symptoms simultaneously. The findings from this study suggest that the provision of information about cancer pain management to patients and their family caregivers is not sufficient to improve pain control in the home care setting. Patients and their family caregivers require ongoing assistance with problem-solving to optimize their pain management regimen.

Around-the-clock (ATC) dosing of opioid analgesics is the established approach for the management of chronic cancer pain. The purposes of this study were to determine whether there were differences in pain intensity scores and pain duration between oncology outpatients who were taking opioid analgesics on an around-the-clock (ATC) compared with an as needed (PRN) basis and to determine differences in opioid prescription and consumption between the 2 groups during a period of 5 weeks. Oncology patients (n = 137) with pain from bone metastasis were recruited from 7 outpatient settings. Patients completed a demographic questionnaire and on a daily basis recorded pain intensity scores and medication intake in a diary. No significant differences in average, least, or worst pain intensity scores or number of hours per day in pain were found between the 2 groups. However, the average total opioid dose, prescribed and taken, was significantly greater for the ATC group than for the PRN group. These findings suggest the need for further investigations in the following areas: the appropriate treatments for pain related to bone metastasis, the use of various pain measures to evaluate the effectiveness of analgesic medications, and the need to evaluate how analgesics are prescribed and titrated for patients with cancer-related pain. © 2002 by the American Pain Society

Purpose/objectives To describe the usefulness of daily pain management diaries to outpatients with cancer who participated in a randomized clinical trial of the PRO-SELF Pain Control Program. Design Randomized clinical trial in which a daily pain management diary was used for data collection in the control group and for data collection and nurse coaching regarding the pain management program in the intervention group. Setting Seven outpatient oncology settings. Sample 155 patients with pain from bone metastases and 90 family caregivers. Methods Content and statistical analysis of audiotaped answers to a semistructured questionnaire. Main research variables Patients' and family caregivers' perceptions of the usefulness of a daily pain management diary; specific ways in which the diary was used. Findings Patients in both the intervention (75%) and control groups (73%) found the diary useful. The diary was used to heighten awareness of pain, guide pain management behavior, enhance a sense of control, and facilitate communication. Family caregivers in both groups also reported that the diary was useful. Conclusions The completion of a daily pain management diary is useful to patients and family caregivers and may function as an intervention for self-care. Implications for nursing Research-based evidence supports the importance of using a daily pain management diary in clinical practice.

e14105 Background: Aurora Kinase A (AURKA) is overexpressed in HNSCC, and correlates with poor prognosis. It has been identified as a potential therapeutic target, yet the response rate for the AURKA inhibitor MLN8237 is only 9% in treatment refractory HNSCC. We hypothesized that although AURKA inhibitors lead to defective spindle assembly, they may also reduce mitotic entry, undermining cytotoxic effect. We predicted that adding a WEE1 inhibitor to an AURKA inhibitor would mitigate this effect and enhance cell death Methods: Cell viability assays were performed on FaDu ( p53 mut.), Detroit562 ( p53 mut.), and UNC7 ( p53 WT) HPV negative HNSCC cell lines treated with AZD1775 (AZD), MLN8237 (MLN), and combination of AZD+MLN. Oncosphere formation assays were used to confirm findings of cell death, and western blot analysis and confocal microscopy were used to investigate mechanism of synergy. The above drugs were also given at varying doses via oral gavage to FaDu xenografted nude mice. Results: There was clear synergy of AZD and MLN in-vitro. Combination Indices were determined by the Chou-Talalay method: FaDu 0.4, Detroit562 0.5, and UNC7 0.6 (synergy = < 0.8). Oncopshere assays showed inability of AZD+MLN treated cells to re-differentiate. FaDu cells treated with MLN had increased p-CDK1 and reduced phospho-histone H3 (pHH3), suggesting reduced mitotic entry. AZD+MLN treated cells had reduced p-CDK1 and increased pHH3, similar to AZD treated cells; they also had spindle disarray with poor chromatin organization on confocal microscopy indicating mitotic catastrophe. In mice, the combination of AZD+MLN inhibited tumor growth, with no apparent toxicity. Mice treated with either drug alone had tumor volumes over 1000mm3 and were sacrificed at day 21; those treated with AZD 90mg/kg and MLN 30mg/kg had tumors volumes around 300mm3 on day 28. Conclusions: AZD and MLN synergistically enhance cell death in HNSCC cell lines and significantly inhibit tumor growth in mouse xenograft models. The ability of AZD to overcome intrinsic resistance to MLN may underlie mechanism of synergy. We recommend further investigation of AURKA and WEE1 inhibition in other cancers with high AURKA expression, and in patients with HNSCC.

PURPOSE: To evaluate oncology outpatients’ level of adherence to their analgesic regimen during a 5-week period. PATIENTS AND METHODS: A random sample of 65 adult oncology outpatients with a Karnofsky performance status score of ≥ 50, an average pain intensity score of ≥ 2.5, and radiographic evidence of bone metastasis were recruited for this longitudinal study from seven outpatient settings. On a daily basis, patients rated their level of pain intensity and recorded pain medication intake. Adherence rates for opioid analgesics prescribed on an around-the-clock (ATC) and on an as-needed (PRN) basis were calculated on a weekly basis. RESULTS: Overall adherence rates for ATC opioid analgesics ranged from 84.5% to 90.8% and, for PRN analgesics, from 22.2% to 26.6%. No significant differences over time were found in either of these adherence rates. CONCLUSION: One factor that seems to contribute to ineffective cancer pain management is poor adherence to the analgesic regimen.

Lung cancer remains a major cause of cancer mortality. Malignant lesions are normally endogenously corrected by the immune surveillance system. However, tumors evade this immunity by inducing immunosuppressive microenvironments during cancer progression. It has been thought that there are two critical components of tumors making them capable of maintaining the immunosuppressive microenvironment. One is the inhibition of cytotoxic T lymphocytes (CTL) activity against the tumor through immune checkpoint molecules, such as programmed death-ligand 1 (PD-L1) and programmed death-1 (PD-1), which are negative regulators of CTL, and the other is by the induction of tumor infiltrating immune suppressive cells, which can deactivate the CTL. Recent studies demonstrate that multiple cancer types, including melanoma, lung, kidney, bladder, and stomach, respond to immune checkpoint inhibitors, such as PD-L1 and PD-1 with 11-30% response rates and durable responses. However, a substantial number of patients still fail to respond to immunotherapy and the refractory mechanisms are largely unknown. In this study, we focus on KRas-driven lung cancers, as there are no clinically effective targeted drugs available for treating this type of lung cancer. We demonstrate that during the progression of tumors in KRas mutation and p53 knockout-driven lung cancer mouse models; KRasG12D/+;p53-/- (KP), there is a gradual increase in the number of myeloid derived suppressor cells (MDSC) and that the combination of either anti-PD-1 or anti-PD-L1 antibody along with a MEK inhibitor, which targets downstream of KRas signaling, shows anticancer efficacy in these animal models. These combinations, in comparison to either single agent alone, effectively blocks the growth of subcutaneously (s.c.) injected syngeneic mouse lung cancer cells in immune competent transgenic KP mice, significantly increasing the survival rates: 37.5% (for anti-PD-1 antibody and MEK inhibitor), 62.5% (for anti-PD-L1 antibody and MEK inhibitor) vs. 0% single agents or control at the end of treatment. We find that the tumors in the control treated group harbor a substantial number of immune cells, including PD-L1 expressing MDSC. The combination treatment with either an anti-PD-1 or anti-PD-L1 antibody along with a MEK inhibitor dramatically modulates the composition and the activity of tumor infiltrated immune cells. Tumors in the combined treated group show a significant decrease in PD-L1 expressing MDSC in comparison with control tumors. Additionally, a combined treatment would block the PD-L1 activity of the infiltrated PD-L1 expressing MDSC in malignant tumors and thus lead to improved survival. These results point to a potential therapeutic opportunity for currently untargetable KRas-driven lung cancers. Citation Format: Jong Woo Lee, Yu Zhang, Hee Sun Park, Sin Aye Park, JaSeok Peter Koo, Roy S. Herbst. Anti-cancer efficacy of the combination with immunomodulatory antibodies and MEK inhibitor for Kras mutation and p53 knockout driven lung cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2334.

Purpose. The economics of acute post-operative pain management are discussed. Studies identifying cost drivers in post-operative pain treatment and the economic sequelae of undertreated pain are reviewed. The relative costs of intermittent intramuscular analgesia, intravenous patient-controlled analgesia, and epidural analgesia are described. Medication errors and their consequences are addressed. The importance of patient satisfaction and data on its correlation with acute post-operative pain are reviewed. Summary. Although the economics of acute post-operative pain treatment are difficult to accurately assess, studies have demonstrated that pharmacy acquisition costs represent as little as 1% of the total hospital cost of surgical treatment. Costs of analgesia are driven largely by staff time. Inadequate treatment of post-operative pain can have important economic ramifications associated with increased patient morbidity, extended hospital stays, and readmissions. Inadequate treatment of post-operative pain is also associated with reduced patient satisfaction, a measure of increasing importance to health systems and pharmacists who practice within them. Conclusion. Undertreatment of acute post-operative pain has important implications for health systems from the standpoints of economics and patient satisfaction.

The transcription factor cyclic AMP-response element-binding protein (CREB) regulates diverse cellular processes, including cell differentiation, proliferation, survival, glucose metabolism, immune regulation, and synaptic plasticity associated with memory. Previously, we showed that CREB is critical on the regulation of mucous differentiation of normal human tracheobronchial epithelial (NHTBE) cells. In addition, the overexpression of CREB is associated with negative prognosis of patients with non-small cell lung cancer (NSCLC). Further studies showed that the knockdown of CREB suppresses the growth of lung cancer cells. It has been demonstrated that genes regulated by CREB have been reported to be involved in the suppression of apoptosis, induce cell proliferation, inflammation and tumor metastasis. However, the critical target genes of CREB in lung cancer have not been well understood. In this study, we identified GSK-3 as one of the CREB target genes critical for the growth and survival of lung cancer cells. The CREB knockdown significantly reduced the expression of GSK-3 and the direct binding of CREB on the promoter of GSK-3 was identified. Kaplan-Meier analysis with a public database showed a prognostic significance of aberrant GSK-3 expression in lung cancer. Inhibition of GSK-3 suppressed cell proliferation, colony formation and tumor growth. Although GSK-3 has been studied as a tumor suppressor in certain types of cancer, there is increasing evidence that GSK-3 plays an oncogenic role in various human cancers. Here, for the first time, we demonstrated that GSK-3 is regulated by CREB in lung cancer and is required for the survival of lung cancer cells. These findings implicate CREB-GSK-3 axis as a novel therapeutic target for lung cancer treatment. Citation Format: Sin-Aye Park, Jong Woo Lee, Roy S. Herbst, Jaseok Peter Koo. GSK-3 is a novel target of CREB and GSK-3-CREB signaling participates in cell survival in lung cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2094. doi:10.1158/1538-7445.AM2015-2094

Compared to the vigorous development of targeted drugs and some of them are already become one of the best treatment of choices in lung adenocarcinoma, squamous lung carcinoma has no definite targets and treatment outcome is not yet superior to lung adenocarcinoma. Demonstration of initial carcinogenesis is benefitial in two aspects: cancer prevention and development of its targets. Studying preneoplastic lesions of bronchus can answer those questions. Preneoplastic lesion, which is considered to have malignant potential, may develop into invasive cancer by escaping from host immune response. CD274 (programmed death-ligand 1, PD-L1) interacts with PD-1, is known to inhibit CD8+ cytotoxic T lymphocyte and induce apoptosis and, also to promote the differentiation of CD4+ T cells into regulatory T cells, so finally evade immune surveillance. We hypothesized that PD-L1 may work as an immune evader in preneoplastic lesion during its carcinogenesis. We performed white light and/or autofluorescence bronchoscopy in patients who have risk factor(s) of lung cancer or are suspected to have a lung cancer. Interestingly, PD-L1 was also overexpressed in preneoplastic lesions especially in severe dysplasia of the bronchus. This finding implies overexpression of PD-L1 can involve at early step of carcinogenesis. Further studies are needed to demonstrate the role of PD-L1 in preneoplastic bronchial lesion potential to develop invasive cancer. Citation Format: Hee Sun Park, Bo Mi Park, Dong Il Park, Chung Jae Uk, Jae Young Moon, Jung Sung Soo, Choong Sik Lee, Ju Ock Kim, Sun Young Kim, Jaseok Peter Koo. Programmed death-ligand 1 is overexpressed in bronchial preneoplastic lesions: can it be a risk indicator. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-092. doi:10.1158/1538-7445.AM2015-LB-092

An understanding of the relationship between the type of analgesic prescription and the prevalence and severity of side effects is crucial in making appropriate treatment decisions. The purposes of this study were: to determine if there were differences in the prevalence of side effects among four different types of analgesic prescriptions (i.e., no opioid, only an as needed (PRN) opioid, only an around-the-clock (ATC) opioid, or an ATC + PRN opioid); to determine if there were differences in the severity of side effects among the four prescriptions groups; and to determine the relationships between the total dose of opioid analgesic medication prescribed and taken and the severity of side effects. As part of a larger study, 174 cancer patients with bone metastasis reported their analgesic use and the prevalence and severity of eleven side effects. Significant differences (P < 0.05) were found in prevalence rates for seven of the side effects among the four prescription groups. The highest prevalence rates were found in the only ATC and ATC + PRN groups. Significant differences were found in the severity scores for five of the side effects, with the highest severity scores reported by patients in the only ATC and ATC + PRN groups. Significant positive correlations were found between the severity of six of the side effects and the total dose of opioid prescribed and taken. Risk factors for analgesic-induced side effects are ATC and ATC + PRN prescription types and higher doses of opioid analgesics.

Purpose/objectives To evaluate the effectiveness of a psychoeducational program (i.e., PRO-SELF Pain Control Program) compared to standard care in increasing patients' knowledge regarding cancer pain management. Design Randomized clinical trial. Setting Seven outpatient settings in northern California. Sample 174 outpatients with cancer and pain from bone metastasis. Methods Following randomization into either the PRO-SELF or standard care group, patients completed the Pain Experience Scale (PES) prior to and at the completion of the intervention. Main research variables Total and individual item scores on the PES. Findings Total PES knowledge scores increased significantly in the PRO-SELF group (21%) compared to the standard care group (0.5%). Significant improvements in knowledge scores for patients in the PRO-SELF group were found on five of the nine PES items when compared to baseline scores. Conclusions The PRO-SELF Pain Control Program was an effective approach to increase patients' knowledge of cancer pain management. Implications for nursing The use of a structured paper-and-pencil questionnaire, such as the PES, as part of a psychoeducational intervention provides an effective foundation for patient education in cancer pain management. Oncology nurses can use patients' responses to this type of questionnaire to individualize the teaching and to spend more time on the identified knowledge deficits. This individualized approach to education about pain management may save staff time and improve patient outcomes.

This abstract is being presented as a short talk in the scientific program. A full abstract is printed in the Proffered Abstracts section (PR03) of the Conference Proceedings. Citation Format: Jong Woo Lee, Hee Sun Park, Sin-aye Park, Roy S. Herbst, Jaseok Peter Koo. Targeting CREB-CBP transcription factor complex using small molecule inhibitors with multifunctional anticancer mechanisms. [abstract]. In: Proceedings of the AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer; 2014 Jan 6-9; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2014;20(2Suppl):Abstract nr B04.

The role of chemokines and chemokine receptors has been evolving in cancer. Besides their functions in the immune system, they also play a critical role in tumor initiation, promotion and progression. Since the tumor microenvironment play a critical role in cancer development and progression, the immune components of the tumor microenvironment have gained attention in the recent decades for its critical role in tumorigenesis and tumor control. Recent studies have clearly demonstrated the importance of CXCR2 in the development of lung cancer. Our recent studies showed that CXCR2 expression in tumor cells was associated with poor prognosis in non-small cell lung cancer (NSCLC) patients (n=262). Analysis of gene expression profiles from the National Cancer Institute (NCI) Director's Challenge Cohort of in lung adenocarcinoma patients (n=442) revealed that overexpression of CXCR2 ligands and CXCR2 genes was clustered together in approximately 25% of lung adenocarcinoma patients. Expression of CXCR2 and its associated ligand gene cluster in tumor cells was associated with poor prognosis, smoking status, and poor histologic differentiation. Furthermore, CXCL5 was involved as an potent angiogenic factor in NSCLC. The objective of the current study was to establish the role of the CXCL5/CXCR2 axis in tumor growth and invasion and to determine its related molecular mechanisms. In the study, CXCL5 activated the CREB transcription factor via the pERK1/2-p90Rsk-pCREB signaling pathway. In addition, inhibitors of CXCR2 and downstream signal transduction molecules blocked the activation of pERK1/2-pRsk-pCREB signaling molecules. Blockade of the CXCR2 receptor, CXCR2-dependent signal molecules, or CREB resulted in suppression of NSCLC cell growth, survival and invasion. These results suggest that the CXCL5-CXCR2-CREB signaling axis may be a source of potential therapeutic targets in lung adenocarcinoma. . Citation Format: Hee Sun Park, Jong Woo Lee, Pierre Saintigny, Jonathan M. Kurie, Roy S. Herbst, Jaseok Peter Koo. Targeting the CXCL5-CXCR2-CREB signaling axis suppresses growth, survival, and invasion of lung adenocarcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2878. doi:10.1158/1538-7445.AM2013-2878

Cyclic-AMP response element-binding protein (CREB)-cAMP response element (CRE) transcriptional pathway plays a critical role in the growth and survival of non-small cell lung cancer (NSCLC) cells. Recruitment of CREB binding protein (CBP) is essential for the transcriptional activity of CREB. However, there is no specific drug in use blocking CREB-CRE transcriptional pathway which may become a new therapeutic target in anti-cancer strategy. Naphthol AS-E phosphate (NASEp) was identified as an inhibitor of CREB transcriptional activity by binding to the KIX domain of CBP and blocking its access to the KID domain in CREB. Our objective was to identify which genes and molecular pathways could be affected by NASEp that may alter target molecules through the regulation of a subset of CRE-containing genes. The effects of the CREB inhibitor NASEp on A549 lung carcinoma cells were examined on an Affymetrix HuGene 1.0 expression microarray and a list of significantly differentially regulated genes was generated. Gene Set Enrichment Analysis (GSEA) shows down-regulation of multiple cancer-related pathways including proliferation, RAS signaling, drug resistance and metastasis. Most significantly, a strong negative correlation with Rosty Cervical Cancer Proliferation Cluster, shows that NASEp inhibits the same set of genes which are up regulated by the E6 and E7 viral oncogenes. These viral elements are known to interact with CBP, which is the direct target of NASEp. Since CBP is known to be a cofactor to multiple transcription factors, we performed an additional round of GSEA using the motif-based Transcription Factor Targets gene set collection and represented the results using a Cytoscape network diagram to illustrate the multifactorial effects of NASEp. Particularly, we focused that several transcription factors regulating cell cycle-related genes. This study implicates potential combinational blockage of CREB and cell cycle-regulated proteins as a cancer therapy. Citation Format: Sin-Aye Park, James Platt, Hee Sun Park, Jong Woo Lee, David F. Stern, Roy S. Herbst, Jaseok Peter Koo. Genome-Wide Gene Expression analysis and molecular portraits regulated by NASEp, an inhibitor of CREB and CBP interaction, in non-small cell lung cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4382. doi:10.1158/1538-7445.AM2013-4382

The cyclic-AMP response element-binding protein (CREB) plays a critical role in the growth and survival of cancer cells as well as cell metabolism. Our previous studies have shown that enhanced CREB activity correlates with increased growth and survival of non-small cell lung cancer (NSCLC) cell lines. In addition, 2-naphthol AS-E phosphate (NASEp), a small molecule inhibitor of CREB, restricted growth of NSCLC cell lines which was associated with reduced expression of pro-angiogenic factors. NASEp distrupts binding of CREB binding protein (CREBBP) to CREB, however, the mechanism which CREB inhibition by NASEp regulates NSCLC cell growth and survival is not fully understood. Here, we found that NASEp inhibited cell growth, survival, anchorage-independent cell growth and invasion, and also completely blocked the expression of Ki-67 and PCNA, markers of cell proliferation in NSCLC cells. Mechanistically, NASEp caused cell cycle arrest at the sub-G1 or G2 phase through down-regulation of several cyclins (cyclin A2, cyclin B1, cyclin D1 and cyclin E2) and led to apoptosis in NSCLC-derived cell lines. Suppression of cyclin D1 was closely related to decreased expression of activator protein-1 (AP-1). Furthermore, in a murine xenograft model, NASEp significantly reduced tumor burden not only by down-regulating of cyclin E2 and PCNA, but also by induction of apoptosis. Taken together, these results suggest that inhibition of CREB activity through dissociation of CREB-CREBBP by NASEp may be a potent new therapeutic in NSCLC. Citation Format: Jong Woo Lee, Hee Sun Park, Seung-Hee Ryu, Patricia Koch, Julie Boyer, Daniel Morgensztern, Roy S. Herbst, Jaseok Peter Koo. Disruption of CREB-CREBBP association by 2-Naphthol AS-E phosphate induces cell cycle arrest and apoptosis in non-small cell lung cancer cells . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3414. doi:10.1158/1538-7445.AM2013-3414