tbuckley/cabot-search huggingface dataset:
Long Noncoding RNA <i>SChLAP1</i> Forms a Growth-Promoting Complex with HNRNPL in Human Glioblastoma through Stabilization of ACTN4 and Activation of NF-κB Signaling
Authors: Jianxiong Ji, Ran Xu, Kaikai Ding, Guoqing Bao, Xin Zhang, Bin Huang, Xinyu Wang, Aurora Martinez, Xiuying Wang, Gang Li, Hrvoje Miletic, Frits Thorsen, Rolf Bjerkvig, Lei Xiang, Bo Han, Anjing Chen, Xingang Li, Jian Wang
Journal: Clinical Cancer Research (2019)

Long noncoding RNAs (lncRNA) have essential roles in diverse cellular processes, both in normal and diseased cell types, and thus have emerged as potential therapeutic targets. A specific member of this family, the SWI/SNF complex antagonist associated with prostate cancer 1 (SChLAP1), has been shown to promote aggressive prostate cancer growth by antagonizing the SWI/SNF complex and therefore serves as a biomarker for poor prognosis. Here, we investigated whether SChLAP1 plays a potential role in the development of human glioblastoma (GBM).RNA-ISH and IHC were performed on a tissue microarray to assess expression of SChLAP1 and associated proteins in human gliomas. Proteins complexed with SChLAP1 were identified using RNA pull-down and mass spectrometry. Lentiviral constructs were used for functional analysis in vitro and in vivo.SChLAP1 was increased in primary GBM samples and cell lines, and knockdown of the lncRNA suppressed growth. SChLAP1 was found to bind heterogeneous nuclear ribonucleoprotein L (HNRNPL), which stabilized the lncRNA and led to an enhanced interaction with the protein actinin alpha 4 (ACTN4). ACTN4 was also highly expressed in primary GBM samples and was associated with poorer overall survival in glioma patients. The SChLAP1-HNRNPL complex led to stabilization of ACTN4 through suppression of proteasomal degradation, which resulted in increased nuclear localization of the p65 subunit of NF-κB and activation of NF-κB signaling, a pathway associated with cancer development.Our results implicated SChLAP1 as a driver of GBM growth as well as a potential therapeutic target in treatment of the disease.
Ultrasound‐Assisted Drug Delivery: Microneedle‐Based Generation of Microbubbles in Cancer Tumors to Improve Ultrasound‐Assisted Drug Delivery (Adv. Healthcare Mater. 17/2019)
Authors: Ashkan Zandi, Mohammad Ali Khayamian, Mohammad Saghafi, Shahriar Shalileh, Pouyan Katebi, Sepanta Assadi, Ali Gilani, Mohammad Salemizadeh Parizi, Shohreh Vanaei, Mohammad Reza Esmailinejad, Fereshteh Abbasvandi, Parisa Hoseinpour, Mohammad Abdolahad
Journal: Advanced Healthcare Materials (2019)

In article number 1900613 by Mohammad Abdolahad and co-workers, in vivo electrochemical microbubble generation by entrance of microneedles to tumor tissue improves the sonoporation and drug delivery in animal models. The work reported herein sheds new light on sonoporation assisted drug delivery by in situ bubbles.
Causes and Predictors of Early Mortality in HIV-Positive and HIV-Negative Patients with Diffuse Large B-Cell Lymphoma
Authors: Sakshi Jasra, Mohammad Kazemi, Daniel Cole, Ana Acuna-Villaorduna, Ioannis Mantzaris, Aditi Shastri, Olga Derman, Noah Kornblum, Ira Braunschweig, Amit Verma, Murali Janakiram
Journal: Blood (2018)
Inhibition of Slug effectively targets leukemia stem cells via the Slc13a3/ROS signaling pathway
Authors: Zhonghui Zhang, Lei Li, Chen Wu, Guoshu Yin, Pei Zhu, Yalu Zhou, Yuanfan Hong, Hongyu Ni, Zhijian Qian, Wen-Shu Wu
Journal: Leukemia (2019)
Investigation of telomerase activity in inflammatory and noninflammatory breast cancer.
Authors: Ayman Maher Salem, Mohamed El-Shinawi, Salwa Farouk Sabet
Journal: Journal of Clinical Oncology (2012)

e21055 Background: Inflammatory breast cancer (IBC) is an aggressive type of breast cancer disease that has a high incidence in Egypt than western countries. It is characterized by rapid progression, involvement of dermal lymphatic emboli and extensive lymph node involvement. Basic and translational studies needed to define IBC disease biology and identify specific biomarkers have been limited by the paucity of patient samples. Hence, the current study aimed to introduce the telomerase activity level as a novel diagnostic marker for breast cancer and specifically for IBC to be differentiated from non-IBC. Methods: Breast cancer patients were enrolled from Ain Shams University hospitals in Cairo, divided into two groups: IBC (n=26) and non-IBC (n=27). Tissue samples were collected during modified radical mastectomy. TRAP (Telomerase repeat amplification protocol) assay was used to assess the telomerase activity in inflammatory and non inflammatory breast cancer tissue samples and their representative cell lines, SUM149 and MCF-7 respectively. Immunohistochemistry was used to investigate the expression of hTERT subunit of telomerase in paraffin embedded tissue samples of both types of patients. MTT assay was used to compare the effect of AZT (3’-azido-3’-deoxythymidine) on the growth of cell lines SUM149 and MCF-7. Results: : IBC showed Telomerase activity ranged from 12 to 376 units with a mean value of 75 and a median value of 43, while telomerase activity in non-IBC ranged from 6 to 109 units with a mean value of 35 and a median value of 24. On the other hand, normal tissues showed telomerase activity below 5 (P &gt; 0.001). Using immunohistochemistry, the hTERT expression was higher in IBC than non-IBC and no expression at all in normal tissues. Also, a positive correlation was found between the telomerase activity and the number of metastatic lymph nodes in both IBC (r =0.511) and non-IBC (r =0.622). Besides, IBC cell line showed a faster response (53%) to telomerase inhibition by AZT after 24 hrs than non-IBC cell line (13%) at the same conditions. Conclusions: Telomerase could be a promising marker at the diagnostic and therapeutic levels in breast cancer and specifically in IBC.
International Society for Nutritional Psychiatry Research Practice Guidelines for Omega-3 Fatty Acids in the Treatment of Major Depressive Disorder
Authors: Ta-Wei Guu, David Mischoulon, Jerome Sarris, Joseph Hibbeln, Robert K. McNamara, Kei Hamazaki, Marlene P. Freeman, Michael Maes, Yutaka J. Matsuoka, R.H. Belmaker, Felice Jacka, Carmine Pariante, Michael Berk, Wolfgang Marx, Kuan-Pin Su
Journal: Psychotherapy and Psychosomatics (2019)

Major depressive disorder (MDD) is a complex mental illness with unmet therapeutic needs. The antidepressant effects of ω–3 polyunsaturated fatty acids (n–3 PUFAs) have been widely reported. The subcommittee of the International Society for Nutritional Psychiatry Research organized an expert panel and conducted a literature review and a Delphi process to develop a consensus-based practice guideline for clinical use of n–3 PUFAs in MDD. The guideline focuses on 5 thematic areas: general concepts, acute treatment strategy, depression recurrence monitoring and prevention, use in special populations, and potential safety issues. The key practice guidelines contend that: (1) clinicians and other practitioners are advised to conduct a clinical interview to validate clinical diagnoses, physical conditions, and measurement-based psychopathological assessments in the therapeutic settings when recommending n–3 PUFAs in depression treatment; (2) with respect to formulation and dosage, both pure eicosapentaenoic acid (EPA) or an EPA/docosahexaenoic acid (DHA) combination of a ratio higher than 2 (EPA/DHA &gt;2) are considered effective, and the recommended dosages should be 1–2 g of net EPA daily, from either pure EPA or an EPA/DHA (&gt;2:1) formula; (3) the quality of n–3 PUFAs may affect therapeutic activity; and (4) potential adverse effects, such as gastrointestinal and dermatological conditions, should be monitored, as well as obtaining comprehensive metabolic panels. The expert consensus panel has agreed on using n–3 PUFAs in MDD treatment for pregnant women, children, and the elderly, and prevention in high-risk populations. Personalizing the clinical application of n-3 PUFAs in subgroups of MDD with a low Omega-3 Index or high levels of inflammatory markers might be regarded as areas that deserve future research.
Engaging care partners in breast cancer care and communication.
Authors: Jennifer Aufill, Jennifer L. Wolff, Diane Echavarria, JaAlah-Ai Heughan, Kimberley T. Lee, Elissa Thorner Bantug, Howard Levy, Sydney M. Dy, Antonio C. Wolff
Journal: Journal of Clinical Oncology (2019)

11614 Background: Family is often overlooked in cancer care. Little is known about the patient preferences for involving family in communication, whether preferences may be elicited and supported at the point of care, and impact on care quality. Methods: We conducted a two-group pilot randomized controlled trial (NCT03283553) of patients on active treatment for breast cancer and the “care partner” who accompanies them to routine visits (n = 132 dyads). Intervention dyads (n = 69) completed a self-administered checklist to clarify the care partner role, establish a shared visit agenda, and facilitate access to the electronic health record (MyChart) patient portal. Control dyads (n = 63) received usual care. Intervention acceptability and short-term effects were assessed from post-visit surveys and MyChart utilization at 6 weeks. Results: At baseline, most patients (89.4%) but few care partners (1.5%) were registered for MyChart. Most patients (79.4%) wanted their care partner to have access to their records and 39.4% of care partners reported accessing it in the past year using the patient’s account login/password. In completing the checklist, intervention patients and care partners identified an active communication role for the care partner and similar issues for the visit agenda: topics most frequently selected were treatment goals/expectations (75.4% &amp; 66.7%, respectively), symptoms/side effects (73.9% &amp; 62.3%) and chances of cancer recurrence/spread (49.3% &amp; 44.9%). More than 90% of intervention participants reported that completing the checklist was easy, useful, and recommended it to others. At 6 weeks, intervention (vs control) care partners were more likely to be registered for MyChart (75.4 % vs 1.6%; p &lt; 0.001), to have logged in (43.5% vs 0%; p &lt; 0.001) and viewed clinical visit notes (30.4% vs 0%; p &lt; 0.001), but no more likely to have exchanged direct messages with the clinical team (1.5% vs 0%; p = 0.175). No difference in patient MyChart registration, use, or messaging was found at 6 weeks, but intervention patients more often viewed clinical visit notes (50.7% vs 9.5%; p &lt; 0.001). Conclusions: A self-administered patient-family communication intervention affected online practices of patients and cancer care partners. Follow-up continues. Clinical trial information: NCT03283553.
Effectiveness of psychological distress reduction with cognitive behavioral therapy for oncological patients: A one-year follow-up study.
Authors: Alessandro Rossi, Maria Marconi, Stefania Mannarini, India Minelli, Monica Anderboni, Chiara Rossini, Giuseppe Di Lucca, Claudio Verusio
Journal: Journal of Clinical Oncology (2019)

11624 Background: Distress has a negative impact on medical treatment (Di Matteo, Lepper &amp; Croghan, 2006) and it is considered one of the most important indexes of psychological suffering in oncological patients (NCCN, 2015). Thus, the purpose of this study was to determine the long term effectiveness of brief Cognitive Behavioral Therapy for patients with cancer (CBT-C) compared with a control group (CG) of oncological patients without any psychotherapy intervention - at one year after a chemotherapy treatment. Methods: Participants ( n = 80; mean age = 63.3, SD = 13.4; 54 female) enrolled at the Oncology Day Hospital at the “Presidio Ospedaliero” of Saronno, ASST Valle Olona, Italy who undertook (CBT-C: n = 40) or non-undertook (CG: n = 40) a psychotherapy intervention. Individual psychotherapy sessions strictly followed the IPOS guidelines (Watson &amp; Kissane, 2017). Participants were tested with the Psychological distress Inventory (PDI) at the baseline (T1; Cronbach α = .88) at the end of the chemotherapy treatment (T2; Cronbach α = .87), at the end of the psychotherapy intervention (T3; Cronbach α = .88), 6-month follow-up (T4; Cronbach α = .85), and 1-year follow-up (T5; Cronbach α = .84). Results: Multilevel growth curve modeling – controlling for age, number of sessions, type and localization of tumor – showed a sharper reduction of distress for CBT-C participants that continue after posttreatment until 1-year follow-up ( p &lt; .001); whereas for CG participants it reduced more gradually from pretreatment to 1-year follow-up ( p &lt; .001). The results revealed a significant difference between the linear slopes for each treatment condition ( p &lt; .001). The overall Hedges’ g comparing the two groups for distress reduction between pretreatment and 1-year follow-up was 2.14 (p &lt; .001) in favor of CBT-C. Conclusions: Given that psychological distress occurs frequently among oncological patients this study is into an important area of study. Results suggest that CBT-C is statistically and clinically effective in treating psychological distress 1 year after the chemotherapy treatment. These findings revealed a kind of long-term effectiveness psychological intervention able both to reduce psychological suffering and improve a better quality of life in oncological settings.
Antithrombotic Therapy in Atrial Fibrillation and Coronary Artery Disease
Authors: Richard C. Becker
Journal: New England Journal of Medicine (2019)

The Food and Drug Administration approved the first direct oral anticoagulant nearly a decade ago. Since then, antithrombotic therapy has evolved swiftly, with research systematically addressing the use of these agents for the treatment of common medical conditions, such as atrial fibrillation. Of particular concern in recent years has been the question of how to manage atrial fibrillation and coronary artery disease when they occur together in the same patient. Yasuda and colleagues1 now report in the Journal the results of the AFIRE (Atrial Fibrillation and Ischemic Events with Rivaroxaban in Patients with Stable Coronary Artery Disease) trial. This multicenter, . . .
P11.64 Specialized neurooncologial biorepository of the N.N. Burdenko National Medical Research Center for Neurosurgery: high-quality tumor bank for personalized medicine
Authors: D Golbin, G Pavlova, M Shifrin, S Shugay, T Tsukanova, A Korochkina, G Danilov
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Specialized biorepositories in neurooncology serve for storage of tissue samples derived from patients with central nervous system (CNS) tumors. In 2016 the new facility was launched for collection of CNS tumor specimens. The principal aim of the repository is preparation of frozen CNS tumor samples accompanied by associated clinical, pathological, molecular, and follow-up data. MATERIAL AND METHODS Each surgical biopsy was divided into several aliquots (usually three), registered, and stored in LN2. Since August 2018 from all aliquots a lesser fragment was separated for paraffin block processing. This histological control was applied for quality assurance of frozen samples. Each specimen record was accompanied with demographic, clinical, perioperative, and histological data. In the follow-up, oncological treatment and response to therapy were added to the databank as well as molecular data. All tumor samples are characterized, passportized, stored, and systemically revised. The following biomarkers were evaluated: Cdk4, Cdk6, FGFR, NANOG, OCT4, SOX2, MELK, Nestin, Notch2, Olig2, GFAP, MAP2, β-III-tubulin, PDGFRA. Dedicated original flexible electronic data storage system was designed for information support of tumor collection. Specimen acquisition, procurement, and storage was encoded using SPREC 2.0 coding system. RESULTS Between March 2016 till January 2019 a total of 596 biopsy samples were stored in the repository. All of them were obtained from the patients operated on in N.N. Burdenko National Medical Research Center for Neurosurgery. Among all entities brain gliomas prevailed and comprised 539 biopsy specimens (90,4%). Specimen quality control using histology, immunohistochemistry, fluorescent in situ hybridization, and molecular methods was performed. The frequency of appropriate aliquots is as high as 83,4%. Tumor sample collection included primary and recurrent cases including those, which underwent primary and secondary in N.N. Burdenko National Medical Research Center for Neurosurgery. CONCLUSION Specialized neurooncological biorepository is advantageous due to possibility of tumor tissue collection at different stages of the disease. The associated databank contains patients’ data, tumor tissue data, treatment data, response to treatment, and follow-up data. Further development of the facility will provide collection of the larger spectrum of neurooncological entities, creation of tumor cell culture bank, and experimental therapies for the development of personalized neurooncological treatment.
Challenges for everyone: Real people, deception, one-shot games, social learning, and computers
Authors: Joseph Henrich
Journal: Behavioral and Brain Sciences (2001)

This commentary suggests: (1) experimentalists must expand their subject pools beyond university students; (2) the pollution created by deception would not be a problem if experimentalists fully used non-student subjects; (3) one-shot games remain important and repeated games should not ignore social learning; (4) economists need to take better control of context; and (5) using computers in experiments creates potential problems.
The effect of aromatase inhibitors on bone mineral density measured by serial DXA scans
Authors: K. J. Whannel, J. C. Doughty, C. R. Wilson, A. McLellan
Journal: Journal of Clinical Oncology (2007)

11065 Background: We are now using aromatase inhibitors (AI) in increasing numbers of women as treatment in the breast cancer care pathway. Studies have reported a loss of bone mineral density (BMD) with use of all AIs. It has been shown in our unit that 5 years of tamoxifen (T) in post-menopausal women prior to commencing an AI does not offer sufficient protection to prevent significant BMD loss when an AI is introduced, with 25% requiring concurrent bisphosphonate (BP) therapy. The aim of this study was to determine changes in serial DXA scan results over a 12month period in women taking AIs. Method: 62 women being considered for or in early stages of use of an AI attended for a DXA scan and re-scan at 12 months. Vertebral morphometry and fracture rate were assessed and risk factors for osteoporosis noted. Scan results were compared ( Table 1 ). Results: Mean age was 67yrs [standard deviation (SD) 9yrs]. The patients were grouped according to initial endocrine therapy. 13 (21%) switched from tamoxifen to arimidex after 2years, 3 (4.8%) switched from tamoxifen to exemestane after 3 years and 30 (48.4%) switched from tamoxifen to letrozole after 5 years. 11 (17.7%) had been on arimidex as first line endocrine therapy for &lt;=2 years and 5 (8.1%) had been on letrozole as first line endocrine therapy for &lt;=1 year. Mean t-score and SD was calculated at each site and results categorised by lowest t-score at any site. The overall decrease in BMD measured at 1.66% over the 12 months. Conclusion: We have demonstrated a decrease in BMD with AI treatment of 1.66% per year as well as an increase in fracture incidence and increased need for bisphosphonate therapy whilst on an AI. We would recommend that all patients on any AI receive annual DXA scans. [Table: see text] No significant financial relationships to disclose.
P11.63 PI3K inhibition in conjunction with the ketogenic diet reduces growth and neuroinflammation in pediatric high-grade glioma
Authors: E Noch, I Yim, L Cantley
Journal: Neuro-Oncology (2019)

Abstract Background: Pediatric high-grade glioma remains a poorly treatable disease with high mortality.Therapeutic advances have lagged behind that of adult glioblastoma, due to small patient numbers, inappropriate generalization from adult tumor types, and unique biology. The use of targeted therapy has recently gained interest in this disease, but efficacy is limited by therapeutic resistance, often as a result of tumor heterogeneity. In the case of phosphatidylinositol 3-kinase (PI3K) inhibition, clinically relevant PI3K inhibitors represent a strong class of drugs for pediatric high-grade glioma, but their use is associated with insulin feedback that reactivates the PI3K pathway and drives therapeutic resistance. Here, we target insulin feedback that is the primary mechanism of PI3K inhibitor-related therapeutic resistance in pediatric high-grade glioma using the ketogenic diet. Materials and Methods: Patient-derived pediatric high-grade glioma stem cells were treated with vehicle or the pan-PI3K inhibitor, BKM-120, with glucose deprivation or phenformin to decrease glucose utilization. NSG mice containing patient-derived pediatric high-grade glioma xenografts were treated with vehicle or BKM-120 on a regular or ketogenic diet to determine whether reducing insulin feedback increases BKM-120 efficacy. To determine the effect of glioma cells on neuro-inflammation, we measured pro-inflammatory cytokines in glioma cells treated with BKM-120 and phenformin in comparison to vehicle-treated cells. We then applied conditioned medium from glioma cells treated with BKM-120 and phenformin to cortical neuronal cultures to measure oxidative stress and neuro-inflammation. Results: Pediatric high-grade glioma cells exhibited increased toxicity when exposed to BKM-120 with glucose deprivation or phenformin. Furthermore, mice with intracranial high-grade glioma xenografts survived longer when treated with BKM-120 on the ketogenic diet than with BKM-120 or the ketogenic diet alone. Phenformin reduced the production of pro-inflammatory cytokines by BKM-120-treated glioma cells. Cortical neurons treated with conditioned medium from BKM-120- and phenformin-treated glioma cells exhibited less oxidative stress than those treated with BKM-120 alone. Our results demonstrate that strategies to lower glucose utilization and insulin feedback increase efficacy of BKM-120 and decrease neuro-inflammation. Conclusions: We show that strategies to lower glucose utilization and insulin feedback increase efficacy of BKM-120. Furthermore, reducing insulin feedback decreases the production of pro-inflammatory cytokines in tumor cells and reduces oxidative stress in neurons treated with conditioned medium from BKM-120-treated glioma cells. By using the ketogenic diet to reduce glucose levels, this strategy may enhance efficacy of PI3K inhibitors in this patient population.