By contrast, knockdown of either FRα or PCFT decreased the cytotoxicity of PTX/Fol-c1 -β-CyD in FRα-expressing SK-OV-3 cells. Furthermore, the cytotoxicity of PTX/Fol-c1 -β-CyD in A2780 cells was increased at acidic pH, and this increase was suppressed by PCFT inhibitor. In mice intraperitoneally inoculated with FRα-expressing or PCFT-expressing EOC cells, intraperitoneal administration of PTX/Fol-c1 -β-CyD significantly suppressed the growth of both types of EOC cells relative to PTX alone, without inducing a significant change in the neutrophil/white blood cell ratio. Our data suggest that Fol-c1 -β-CyD targets not only FRα but also PCFT, and can efficiently deliver anticancer drugs to EOC cells in the peritoneal cavity. This article is protected by copyright. All rights reserved.OBJECTIVE Cancer diagnosis in adolescents and young adults (AYAs) coincides with the developmental initiation of substance use and emergence of affective disturbance. We examined substance use behaviors and risk-stratified associations with mental and physical health, as well as objective indicators of tobacco and cannabis use and concordance with self-report and medical records. PD 0332991 METHODS AYAs were 15 to 39 years at cancer diagnosis and ≥18 years and ≥6 months postdiagnosis at study enrollment. Risk-stratified groups included nonsmoker/nondrinker, nonsmoker/drinker, smoker/drinker. Assessments included demographics, past year tobacco, alcohol, and cannabis use, depression, anxiety, sleep, and physical activity. Urine analysis provided biochemical verification of tobacco and cannabis use. RESULTS Participants included 100 AYAs (60% male) with primarily hematological cancers (88%). Past year alcohol, tobacco, and cannabis use prevalence rates were 80%, 15%, and 33%, respectively. A minority (non-users) refrained from both alcohol and tobacco (20%), while most were exclusively alcohol users (65%) or alcohol and tobacco co-users (15%). Relative to other sub-groups, co-users reported more depressive and anxious symptoms, while non-users reported more physical activity. More frequent tobacco and cannabis use were associated with more depressive and anxious symptoms, while more frequent alcohol use was associated with lower physical activity. There were no group differences or associations with sleep quality. There was considerable discordance between tobacco use self-report, biochemical verification, and medical record documentation. CONCLUSIONS Substance use among AYAs is common and detrimental to mental and physical health, especially among more frequent users and co-users, highlighting the need for early assessment and intervention. © 2020 John Wiley & Sons, Ltd.LESSONS LEARNED The fibrolamellar carcinoma-associated DNAJB1-PRKACA gene fusion transcript RNA codes for the catalytic domain of protein kinase A and, thus, overexpression of Aurora kinase A. ENMD-2076 showed a favorable toxicity profile. The limited results, one patient (3%) with a partial response and 57% of patients with stable disease, do not support further evaluation of ENMD-2076 as single agent. Future studies will depend on the simultaneous targeting approach of DNAJB1-PRKACA and the critical downstream components. BACKGROUND Fibrolamellar carcinoma (FLC) represents approximately 0.85% of liver cancers. The associated DNAJB1-PRKACA gene fusion transcript RNA codes for the catalytic domain of protein kinase A and overexpression of Aurora kinase A (AURKA). ENMD-2076 is a selective anti-AURKA inhibitor. METHODS Patients aged >12 years with pathologically confirmed incurable FLC, with measurable disease, Eastern Cooperative Oncology Group performance status 0-2 or Lansky 70-100, and adequate organ functimary is the property of the authors.OBJECTIVE Specific personality traits are associated with differential use of various coping strategies. Few studies have examined the relationship between personality and coping in oncology patients undergoing chemotherapy. We, therefore, examined the relationship between previously identified personality profiles (ie, Distressed [14.3% of total sample], Normative [53.8%], Resilient [31.9%]) and measures of coping and adjustment. METHODS Patients (n = 1248) undergoing chemotherapy for breast, gastrointestinal, gynecological, or lung cancer completed measures of personality (NEO-Five Factor Inventory), coping (Brief COPE), and psychological adjustment to cancer (Mental Adjustment to Cancer [MAC] scale). Differences in coping and adjustment among the three personality profiles were evaluated using analysis of variance. RESULTS On the Brief COPE, the Distressed class endorsed lower use of Active Coping, Positive Reframing, Acceptance, Emotional Support (ie, „engagement” coping); and greater use of Denial, Venting, Behavioral Disengagement, Self-Blame (ie, „disengagement” coping) compared to the Normative and Resilient classes. link2 On the MAC scale, the Distressed class scored higher on Anxious Preoccupation, Helplessness/Hopelessness, Fatalism, and Avoidance, and lower on Fighting Spirit, compared to the other two classes. CONCLUSIONS In this sample of oncology patients receiving chemotherapy, patients in the Distressed personality class showed a reduced repertoire of adaptive coping strategies, while those in the Resilient class reported greater use of adaptive or engagement coping strategies. Further work should examine the potential mediating or moderating role of coping and adjustment in the relationships between personality and patient outcomes. Interventions to enhance beneficial and reduce harmful coping strategies in cancer patients should be evaluated. © 2020 John Wiley & Sons, Ltd.OBJECTIVE To investigate the relationships between self-reported and objectively measured cognitive function prior to systemic therapy and subsequent well-being outcomes over 24 months in older breast cancer survivors. METHODS Data were from 397 women aged 60 to 98 diagnosed with non-metastatic breast cancer in the Thinking and Living with Cancer Study recruited from 2010-2016. Cognitive function was measured at baseline (following surgery, prior to systemic therapy) using neuropsychological assessments of attention, processing speed, and executive function (APE), learning and memory (LM), and the self-reported FACT-Cog scale. Well-being was measured using the FACT-G functional, physical, social, and emotional well-being domain scales at baseline and 12 and 24 months later, scaled from 0 (low) to 100 (high). Linear mixed-effects models assessed the relationships between each of baseline APE, LM, and FACT-Cog quartiles with well-being scores over 24 months, adjusted for confounding variables. RESULTS At baseline, older survivors in the lowest APE, LM, and FACT-Cog score quartiles experienced poorer global well-being than those in the highest quartiles. At 24 months, older survivors tended to improve in well-being, and there were no differences according to baseline APE or LM scores. At 24 months, mean global well-being was 80.3 (95% CI 76.2-84.3) among those in the lowest vs 86.6 (95% CI 83.1-90.1) in the highest FACT-cog quartile, a clinically meaningful difference of 6.3 points (95% CI 1.5-11.1). CONCLUSIONS Among older breast cancer survivors, self-reported, but not objective cognitive impairments, were associated with lower global well-being over the first 2 years of survivorship. © 2020 John Wiley & Sons, Ltd.The incidence of mesenchymal tumors in the salivary gland range from 0.3-1%1 . link3 Adamantinoma like Ewing sarcoma (ALES) is an unusual variant of Ewing sarcoma with more incidences in the head and neck of young patients, however scarce in salivary gland2 . This article is protected by copyright. All rights reserved.PURPOSE To develop a registration method that is capable of estimating the full range of rigid body motion from three orthogonal collapsed images of the head. These images can be obtained using the collapsed FatNav, a previously introduced navigator for prospective motion correction. It combines a short duration with wide compatibility with different main sequences due to its robustness against spin history effects. THEORY AND METHODS A projection-based 3D/2D registration method is presented and then modified to take into account the peculiarities of the collapsed FatNav. Water/fat separated volumes were used in simulations to assess the accuracy of the proposed method at different resolutions by comparison with high-resolution 3D registration. The sensitivity with respect to masking strategies and starting motion parameters was investigated. Finally, prospective experiments with a healthy volunteer were performed with different types of motion patterns. A PROPELLER main sequence was chosen to compare the prospective correction with PROPELLER’s own retrospective correction. RESULTS In the simulations the proposed method has shown comparable performance to 3D registration. Furthermore, evidence of its robustness with respect to masking strategies and starting motion parameters was presented. The combination with collapsed FatNav has performed well in correcting most of the motion artifacts prospectively with improved image quality compared to only using PROPELLER’s retrospective motion correction. CONCLUSIONS The proposed 3D/2D registration together with collapsed FatNav is characterized by a good balance between navigator duration and estimate accuracy. Further work is needed to validate the method across a wider variety of subject anatomies. © 2020 International Society for Magnetic Resonance in Medicine.Pseudo-isocyanine chloride (PIC) is a dyestuff which self-assembles in aqueous solution, thereby showing a characteristic and sharp absorption band as well as a fluorescence band at a wavelength of 573 nm. Based on this unique feature, a synthetic model system was developed, suitable to analyse self-assembly in various environments like macromolecular crowding. First, Triethylene glycol (TEG), polyethylene glycol (PEG), Ficoll 400 as a highly branched polysaccharide and sucrose corresponding to the monomeric unit of Ficoll were used as potential crowders. Combined UV-Vis spectroscopy and time-resolved light scattering revealed a strong impact of crowding based on excluded volume effects only for Ficoll 400. Sucrose had hardly any influence on the self-assembly of PIC and PEG and TEG impeded the PIC self-assembly. Finally, HeLa cells were infiltrated with PIC solutions well below the aggregation threshold in the infiltrating solution. In the cellular environment, PIC was exposed to a significant crowding and immediately started to aggregate. As was demonstrated by fluorescence imaging, the extent of aggregation could be modulated by exposing the cells to salt-induced osmotic stress. The results suggest future use of such a system as a sensor for the analysis of in vitro and in vivo crowding effects on self-assembly processes. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Conjugation of small molecule drug to lipid-polymer amphiphiles is a powerful strategy to alter the pharmacokinetic profile of these molecules by promoting binding to albumin or other serum molecules. Incorporation of a responsive linker between the lipid anchor and the polymer chain can be of interest to avoid indefinite binding of the conjugates to hydrophobic pockets of serum proteins or phospholipid membranes when reaching a target cell or tissue. Here, the synthesis of pH-sensitive lipid-polymer conjugates by reversible addition-fragmentation chain transfer (RAFT) polymerization using a RAFT chain transfer agent that is equipped with a pH-sensitive ketal bond between a cholesterol moiety and the trithiocarbonate RAFT chain transfer group is reported. It is demonstrated that in native form these conjugates exhibit a high affinity to albumin and cell membranes but loose this ability in response to a mild acidic trigger in aqueous medium. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.