tbuckley/cabot-search huggingface dataset:
Abstract 18621: Self-care Confidence is Important in Self-care in Emerging Adults With Congenital Heart Disease
Authors: Desiree Fleck, Janet Deatrick, Victoria V Dickson, Terri Lipman, Gary Webb, Barbara Riegel
Journal: Circulation (2015)

Background: Emerging adults (ages 18-25 years) with congenital heart disease (CHD) are expected to perform self-care, behaviors that maintain physiologic stability and the response to symptoms as they occur. In spite of the seriousness of CHD, some emerging adults forego self-care. Identifying those unlikely to perform self-care is essential.Objective: The purpose of this study was to describe self-care and to identify the correlates of self-care in emerging adults with CHD. We hypothesized that knowledge and beliefs would be the primary determinants of self-care. Methods: In this descriptive, cross-sectional study, we enrolled a convenience sample (n=57) of emerging adults from two outpatient CHD centers (adult, n=37; pediatric, n=20) in the Northeastern US. All participants completed neuropsychological testing (PMR, DSST, Trail-Making Tests and the Letter Number Sequencing Tests) and scales measuring developmental stage (Course of Life), mood, knowledge of CHD (Leuven Knowledge Questionnaire), self-efficacy (the NGSES), family functioning (FAD), and a demographic survey. Disease severity was determined by the diagnosis and the number of repairs. Variables were tested as correlates of self-care measured using the Self-Care in CHD Scale (SC-CHD). Scores are standardized 0-100; higher scores indicate higher self-care. Multivariate regression was conducted in two blocks. First age, disease severity, developmental stage, mood, family functioning, cognition, and self-care confidence were entered. Second, knowledge and beliefs were entered for hypothesis testing. Results: Participants (42% female, mean age 21 years, SD 2.32) had predominantly moderate (42%) to severely (45.6%) complex CHD. Self-care was low (SC-CHD=mean 57, SD 11.23). More CHD repairs, higher levels of self-care confidence, and older age explained 41% of the variance in self-care (Block 2: F=3.785, df=3, 46, p=0.17). The higher the level of self-care confidence, the more likely the performance of self-care. Conclusions: These results can be used to identify a subset of CHD patients at risk for poor self-care. Self-care confidence is the only modifiable determinant, suggesting that interventions designed to increase self-care confidence may be useful in this population.
ACTR-72. IDH-WILD TYPE GRADE II GLIOMAS: A RETROSPECTIVE SERIES OF ITALIAN ASSOCIATION OF NEURO-ONCOLOGY
Authors: Roberta Rudà, Francesco Bruno, Alessia Pellerino, Antonio Silvani, Tamara Ius, Lorenzo Bello, Giuseppe Minniti, Andrea Pace, Giuseppe Lombardi, Riccardo Soffietti
Journal: Neuro-Oncology (2018)

Information regarding clinical characteristics and response to treatments of IDH-wild type grade II gliomas are still lacking. MATERIAL AND We performed a retrospective study on patients with WHO grade II IDH wild type gliomas recruited from 1999 to 2017 in six Italian Institutions. IDH mutation was assessed by either immunohistochemistry or sequencing (in case of negative immunohistochemistry). Exclusion criteria were the presence of minimal anaplastic foci or radiological features of HGGs. Kaplan-Meier curves and Cox-regression models were used for univariate and multivariable analysis. Out of 194 patients 122 met the inclusion criteria. Median age was 45 years. Non-enhancing tumours on MRI accounted for 74% while 26% had mild contrast enhancement. Surgery consisted in gross total resection in 29%, partial/subtotal in 45%, biopsy in 24%, and unknown in 2%. According to WHO 2007 astrocytomas were 44%, oligodendrogliomas 35%, and oligoastrocyomas 21%. Post-surgical management consisted in observation with MRI in 42%, chemoradiation in 21%, chemotherapy alone in 21%, radiotherapy alone in 5%, radiotherapy followed by chemotherapy in 5%, and 6% unknown. Median time of follow-up was 31 months. Median PFS at first recurrence from diagnosis was 24.0 months (1.2 147.0). Treatments at recurrence consisted in second line chemotherapy in 33 cases (42.3%), second surgery in 18 cases (23.1%), radiotherapy in 10 cases (10.4%), and palliative care in 13 cases (16.7%). Median OS was 45.3 months (1.0 225.6). Factors associated with longer PFS and OS in univariate analysis were younger age, absence of contrast enhancement, and gross total resection. Younger age and gross total resection retained the statistical significance in multivariable analysis. WHO grade II IDH-wild type gliomas have a worse outcome as compared with IDH-mutant tumours. This is the first real life study reporting that gross total resection improves the outcome.
NCMP-03. RISK FACTORS FOR SURGICAL SITE INFECTIONS AFTER CRANIOTOMY FOR PRIMARY BRAIN TUMORS
Authors: Paul Krafft, Nam Tran, Corin Agoris, Quan Tran, Solmaz Sahebjam
Journal: Neuro-Oncology (2018)

Surgical site infection (SSI) after craniotomy for primary CNS tumors can have detrimental consequences by delaying chemoradiation treatment. The authors performed a retrospective chart review of all patients who underwent craniotomies for resection of primary brain tumors at the Moffitt Cancer Center from 2004–2014. Multivariate logistic analysis was used to identify independent risk factors. A total of 864 patients underwent craniotomies for primary brain tumors, but 65 were excluded due to insufficient followup or incomplete records. We identified 30 patients with SSI (3.8%). The most common microorganisms isolated from SSI were methicillin resistant Staphylococcus aureus (40%), methicillin sensitive Staphylococcus aureus (17%), methicillin resistant Streptococcus epidermidis (7%), Pseudomonas (7%), Enterobacteriaceae (7%), and E coli (7%). During the latter part of this time period, we initiated a program of intraoperative topical vancomycin application. We observed a significant reduction in SSI among those receiving topical vancomycin compared to those without (0.8% vs 4.9%, p<0.001). The cohorts were similar in demographics and baseline comorbidities, KPS, tumor characteristics, and surgical factors. We identified length-of-stay, previous radiation and preoperative steroid dose as independent risk factors for SSI. Thus, our study identifies potential modifiable risk factors for the prevention of SSI in patient undergoing craniotomy for primary CNS tumors.
Abstract 20139: Loss of Sam68 Attenuates Inflammatory Response in Injured Arteries and Enhances Recovery
Authors: Shuling Han, Junlan Zhou, Gangjian Qin
Journal: Circulation (2016)

Background: The role of Src-associated in mitosis 68 kDa (Sam68) protein in cardiovascular biology is unknown. We sought to determine whether Sam68 regulates vascular remodeling after injury. Metho...
IMMU-53. IMPACT OF TUMOR-TREATING FIELDS (TTFIELDS) ON THE IMMUNOGENICITY OF GLIOMA CELLS
Authors: Manuela Silginer, Michael Weller, Patrick Roth
Journal: Neuro-Oncology (2018)

TTFields have been tested in phase III trials in recurrent and in newly diagnosed glioblastoma patients. However, the impact of TTFields on the tumor microenvironment and on interactions between tumor cells and the immune system remain poorly characterized. Thus, we investigated the interaction of TTFields with molecules involved in immune responses as well as drugs that may modulate immune cell activity such as dexamethasone. Natural killer group 2 member D (NKG2D) ligand mRNA expression was determined by RT-PCR. NKG2D ligand, MHC class I and class II, and calreticulin (CRT) protein levels were assessed by flow cytometry and high-mobility group protein 1 (HMGP-1) levels by immunoblot analysis. Immune cell-mediated glioma cell lysis was determined using a flow cytometry-based cytotoxicity assay. We noticed increased NKG2D ligand expression and enhanced NK cell-based killing of glioma cells exposed to TTFields while MHC class I and class II expression remained unaltered. The observed increase in calreticulin exposure upon TTFields treatment may point to enhanced immunogenicity of dying glioma cells, known as immunogenic cell death. Exposure to TTFields may change the immunogenicity of glioma cells which might be exploited for combinatorial approaches with immunotherapeutic agents. Better understanding of the mode of action of TTFields is important for further clinical development.
Efficacy of a paclitaxel-eluting biliary metal stent with sodium caprate in malignant biliary obstruction: a prospective randomized comparative study
Authors: Sung Ill Jang, Kyu Taek Lee, Jung Sik Choi, Seok Jeong, Don Haeng Lee, Yong Tae Kim, Sang Hyub Lee, Jeong-Sik Yu, Dong Ki Lee
Journal: Endoscopy (2018)

Abstract Backgrounds The placement of a self-expandable metal stent (SEMS) is widely used in patients with unresectable malignant biliary obstructions, but SEMSs are susceptible to occlusion by tumor ingrowth or overgrowth. The efficacy and safety of a novel paclitaxel-eluting biliary metal stent incorporating sodium caprate (MSCPM-III) were compared prospectively with those of a covered metal stent (CMS) in patients with malignant biliary obstructions. Methods Patients with unresectable distal malignant biliary obstructions (n = 106) were prospectively enrolled in this study at multiple treatment centers. Stents were placed endoscopically: MSCPM-III in 54 patients and CMS in 51 patients. The patients received systemic chemotherapy regimens according to their disease characteristics. Results The two groups did not differ significantly in basic characteristics or mean follow-up period. Stent occlusion occurred in 14 patients who received MSCPM-III and in 11 patients who received CMS. Time to recurrent biliary obstruction (RBO) and survival time did not differ significantly between the two groups (P = 0.84 and P = 0.29, respectively). However, tumor size at 2 months after stent insertion was significantly decreased in patients in the MSCPM-III group with bile duct cancers or those who experienced stent migration compared with the CMS group. Complications, including cholangitis and pancreatitis, were found to be acceptable in both groups. Conclusions Although compared with a CMS the MSCPM-III did not significantly influence time to RBO or survival duration in patients with malignant biliary obstructions, MSCPM-III reduced tumor volume and was used safely in humans.
TMIC-15. OMX IS A TUMOR MICROENVIRONMENT MODIFIER THAT RESTORES ANTI-TUMOR IMMUNITY AND IMPROVES ANTI-TUMOR EFFICACY BY REDUCING TUMOR HYPOXIA IN INTRACRANIAL GLIOBLASTOMA MOUSE MODEL
Authors: Natacha Le Moan, Tina Davis, Philberta Leung, Sarah Ng, Jonathan Winger, Stephen Cary, Nicholas Butowski, Ana Krtolica
Journal: Neuro-Oncology (2018)

Intratumoral hypoxia is associated with resistance to chemo- and radio-therapies and poor patient outcomes. In addition, hypoxia promotes the immune escape of tumors by altering the recruitment and function of innate and adaptive immune effector and suppressor cells. Therefore, reversing tumor hypoxia to create an immunopermissive microenvironment may improve anti-tumor response, and combined with immunotherapy approaches such as checkpoint inhibitors (CPI) may increase therapeutic efficacy. OMX, an anti-cancer therapy designed to reverse tumor hypoxia, efficiently accumulates in orthotopic rodent GB and spontaneous canine brain tumors, reduces tumor hypoxia and enhances immunotherapeutic efficacy. We used in vivo bioluminescence imaging of tumor, immunohistochemistry, flow cytometry, and cytokine multiplex assays to evaluate OMX’s ability to immunosensitize the GL261 brain tumor microenvironment and promote tumor cures. Following intravenous administration in brain tumor-bearing mice, OMX reduces tumor hypoxia, modulates the IFNg signaling pathway, enhances the infiltration of tumor-specific CX3CR1+ CD8 T cells into the tumor (using the EphA2 as a GL261-specific tumor antigen), increases the activation of cytotoxic T lymphocytes (CTLs), decreases Tim3 and Lag3 exhaustion markers on CD8 T cells, and reduces the number of immunosuppressive cells such as MDSCs and Tregs in the tumor. Similar immunological changes are observed when OMX is combined with anti-PD-1. In late-stage tumor-bearing mice, we observed a 40% tumor cure rate for the combination of OMX with anti-PD-1, while anti-PD-1 alone resulted only in 5% tumor cures. Following rechallenge with GL261 tumor cells injected on the other side of the brain, all mice treated with the combination of OMX with anti-PD-1 survived, indicating the presence of long-term immunological memory against glioma cells. By delivering oxygen specifically to the hypoxic tumor microenvironment, OMX may restore anti-cancer immune responses in GB patients and synergize with radiotherapy and immunotherapy to enhance tumor control and improve patient outcomes.
QOLP-07. QUALITY OF LIFE IN PATIENTS WITH MENINGIOMA
Authors: Maryam Shahin, Stephen Magill, Jennifer Viner, Michael McDermott
Journal: Neuro-Oncology (2018)

Meningiomas are the most common primary central nervous system tumor, and patients typically live for many years after diagnosis and treatment. Traditionally, patient outcomes are recorded from a clinician’s standpoint, including extent of resection, surgical/radiation complications, progression-free survival, and tumor recurrence. Outcomes from this standpoint will underestimate the impact of disease and treatment on a patient’s quality of life. Thus, we have started a multi-institutional prospective study to assess the quality of life in patients with meningioma. A quality of life instrument (QoL-MNG) was developed using questions from the Functional Assessment of Cancer Treatment-Meningioma (FACT-MNG) tumor site specific instrument on a web-based platform. A pre-operative baseline questionnaire is collected for all patients. Subsequently, patients are assigned to treatment (surgery or radiation) or observation groups. All patients complete a baseline questionnaire. The treatment group completes questionnaires at 3-, 6-, 12-, 18-month, and then annually following surgery or radiation. The observation group completes annual questionnaires. Clinical outcomes data are collected at each time point. To date, 55 patients from a single-institution are actively enrolled and have completed baseline questionnaires in the QoL-MNG study using the online-based interface. Approval for the study has been obtained at 18 other sites. We will present patient level data from our first 14 patients who have completed follow up questionnaires. This includes outcomes in physical well-being, social/family well-being, emotional well-being, functional well-being and tumor site specific questions in the following tumor locations: cerebellopontine angle, parasagittal, petroclival, sphenoid wing, and convexity. CONCLUSIONS: Assessing quality of life is fundamental to improving care for patients with meningioma. These are the first preliminary results of our prospective study which we have expanded to eighteen institutions across North America and Europe with the goal of improving our understanding the impact of meningioma on quality of life.
Protein Kinase C Mu (PKC Mu) interacts with E-Cadherin and Beta-catenin in prostate cancer (PC) in vitro and in vivo
Authors: Meena Jaggi, Prema S. Rao, David J. Smith, George P. Hemstreet, Kethandapatti C. Balaji
Journal: Cancer Research (2004)

5147  We had earlier demonstrated that PKC Mu, a novel isozyme of the PKC family of signal transduction proteins, is down regulated in androgen independent (AI) PC. Because PKC Mu is uniquely constitutively membrane bound compared to other members of the PKC family, we explored its interaction with the membrane associated cadherin-catenin complex of proteins, which are involved with tumorogenesis and metastasis. We studied the interaction in androgen dependent (AD) LNCaP prostate cancer cells by Immunofluorescence (IF) and Immunoprecipitaion (IP) assays. In Vivo IF assay was done by culturing cells on glass coverslips for 48h, permeabilized with cold methanol, incubated with PKC Mu (C-20) and E-cadherin (HECD1) or Beta-catenin (6F9) antibodies, treated with FITC-conjugated secondary antibodies and analyzed with a LSM 510 laser scanning microscope. For IP assays, protein lysate was obtained from 80% confluent cells, immunoprecipitated with PKC Mu (C-20) and immunoblotted with E-cadherin (HECD1) or Beta-catenin (6F9) antibodies. Reciprocal IP was done with E-cadherin (HECD1) and immunoblotted with PKC Mu (C-20) antibodies. Confocal microsocopy demonstrated that PKC Mu localized to the cell membrane and cytoplasm in the peri-nuclear areas. PKC Mu co-localized with E-cadherin and Beta-catenin at cell-to-cell junctional areas. Both IP and reciprocal IP experiments confirmed that PKC Mu interacted with E- cadherin and IP assay confirmed that PKC Mu also interacted with Beta-catenin. Because E-cadherins are well known to strongly interact with Beta-catenin, the PKC Mu may interact either directly or indirectly with the members of the cadherin-catenin complex of proteins. Our studies have identified a novel interaction between PKC Mu and cadherin-catenin complex of proteins in vivo and in vitro. The functional significance of PKC Mu in PC is currently unclear. It is conceivable that dysregulation of PKC Mu expression in PC may contribute to PC progression by its interaction with the cadherin-catenin complex of proteins, which are well established markers of cancer progression in other malignancies.
Interpreting clinical trial data in multiple myeloma: translating findings to the real-world setting
Authors: Paul G. Richardson, Jesus F. San Miguel, Philippe Moreau, Roman Hajek, Meletios A. Dimopoulos, Jacob P. Laubach, Antonio Palumbo, Katarina Luptakova, Dorothy Romanus, Tomas Skacel, Shaji K. Kumar, Kenneth C. Anderson
Journal: Blood Cancer Journal (2018)

Abstract Substantial improvements in survival have been seen in multiple myeloma (MM) over recent years, associated with the introduction and widespread use of multiple novel agents and regimens, as well as the emerging treatment paradigm of continuous or long-term therapy. However, these therapies and approaches may have limitations in the community setting, associated with toxicity burden, patient burden, and other factors including cost. Consequently, despite improvements in efficacy in the rigorously controlled clinical trials setting, the same results are not always achieved in real-world practice. Furthermore, the large number of different treatment options and regimens under investigation in various MM settings precludes the feasibility of obtaining head-to-head clinical trial data, and there is a temptation to use cross-trial comparisons to evaluate data across regimens. However, multiple aspects, including patient-related, disease-related, and treatment-related factors, can influence clinical trial outcomes and lead to differences between studies that may confound direct comparisons between data. In this review, we explore the various factors requiring attention when evaluating clinical trial data across available agents/regimens, as well as other considerations that may impact the translation of these findings into everyday MM management. We also investigate discrepancies between clinical trial efficacy and real-world effectiveness through a literature review of non-clinical trial data in relapsed/refractory MM on novel agent−based regimens and evaluate these data in the context of phase 3 trial results for recently approved and commonly used regimens. We thereby demonstrate the complexity of interpreting data across clinical studies in MM, as well as between clinical studies and routine-care analyses, with the aim to help clinicians consider all the necessary issues when tailoring individual patients’ treatment approaches.
TMIC-51. DEXAMETHASONE DRIVES MYELOID-DERIVED SUPPRESSOR CELL ACCUMULATION IN GLIOBLASTOMA IN A SEX-SPECIFIC MANNER
Authors: Defne Bayik, Tyler Alban, Daniel Silver, Chihyun Park, Emily Serbinowski, Dionysios Watson, Tae Hyun Hwang, Michael Vogelbaum, Justin Lathia
Journal: Neuro-Oncology (2018)

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immunosuppressive cells consisting of monocytic (M-MDSC) and granulocytic (G-MDSC) subsets that accumulate in tumors, where they constrain anti-tumor immunity. High MDSC frequency in tumor and blood correlates with poor glioblastoma (GBM) prognosis and limits patient response to conventional and immunotherapy treatment strategies. Therefore, understanding factors regulating the dynamic behavior of MDSCs can improve the treatment of GBM. We examined the impact of sex as a biological variable and dexamethasone (DEX) use as a standard disease management strategy on glioma-associated MDSCs activity. Our results showed that M-MDSC and G-MDSC had unique gene signatures and were differentially recruited to mouse GBM tumors. Despite increased G-MDSC production in the bone marrow of tumor-bearing mice, M-MDSCs infiltrated tumors at a higher rate. This frequency was especially higher in male mice, which reached morbidity endpoint earlier than female mice. Under in vitro culture conditions favoring myeloid cell polarization, DEX improved the generation MDSCs from bone marrow precursors by >4-fold; and increased the frequency of resting M0 and immunosuppressive M2 macrophages by 2-fold. DEX also blocked MHC Class II expression in pro-inflammatory M1 macrophages, impairing antigen presentation. These results were validated in a preclinical model of GBM. Daily DEX administration to tumor-bearing mice accelerated the onset of disease-related neurological symptoms and elevated the frequency of M-MDSCs in tumors of male mice. This change in the tumor immune profile was accompanied by reduction of pro-inflammatory mediators IL-12p70, TNFa and IP-10 in plasma, and increased levels of G-CSF, a strong stimulator of MDSCs. Our findings suggest that standard disease management with DEX may augment the immunosuppressive tumor microenvironment, which could be reversed by targeting MDSCs. Sex-related immunological differences can also enable the development of personalized medicine approaches that seek to effectively activate the immune system to attenuate tumor growth.