tbuckley/cabot-search huggingface dataset:
Abstract 3049: Tumor treating fields induce DNA damage and apoptosis in medulloblastoma
Authors: Ryan T. Nitta, Gordon Li
Journal: Cancer Research (2021)

Abstract Medulloblastoma (MB) is the most common malignant brain tumor in children and accounts for approximately 20% of all pediatric central nervous system tumors. Current multimodal treatment has led to a 70-90% five-year overall survival rate, however, the prognosis for patients with tumor dissemination and recurrent MB remains poor. Additionally, the majority of survivors exhibit long-term neurocognitive and neuroendocrine complications because of the cytotoxic drugs and high dose radiation. Consequently, more effective and less toxic treatments are necessary in order to raise the quality of life for these young patients. Tumor Treating Fields (TTFields) are an exciting new therapeutic opportunity for MB. TTFields are low intensity, alternating electric fields that disrupt cell division through physical interactions with key molecules during mitosis. The side effects from TTFields treatments are incredibly low, making it an ideal candidate for MB therapy. Currently TTFields were found to increase the survival of adult brain tumor patients by dysregulating the cytoskeletal network leading to mitotic arrest and as well as other varied multi-modal mechanisms of action. To determine if TTFields can be an effective treatment for MB, we conducted an in vitro study treating multiple MB cell lines with TTFields. We discovered that TTFields treatment reduced MB cell growth (Daoy, Med1-MB, D425, and D283) with an optimal frequency of 200-250 kHz. We also observed that TTFields treatment dysregulated actin polymerization that corresponded with a reduction in cell motility and invasion. TTFields treatment also caused DNA damage (γH2AX, 53BP1) that correlated with an increase in apoptotic cells. To expand on these initial findings, we conducted a combinatorial study with the small molecule inhibitor, CX-4945. CX-4945 is an inhibitor to casein kinase 2 and is currently being used in a phase I clinical trial to treat recurrent MB (NCT03904862). We discovered that CX-4945 enhanced the growth reduction of TTFields treatment. In addition, combining CX-4945 and TTFields increased the number of cells with dysregulated actin which correlated with a decrease in MB migration and invasion. Our findings demonstrate that TTFields may be a novel and less toxic method to treat MB patients. Citation Format: Ryan T. Nitta, Gordon Li. Tumor treating fields induce DNA damage and apoptosis in medulloblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 3049.
Abstract 1960: Mechanisms of therapeutic synergy between pattern recognition response agonists and cdk4 inhibitors
Authors: Victoria Roulstone, Joan Kyula, Richard Elliot, Christopher J. Lord, Nik Matthews, Vicki Jennings, Harriet Whittock, David Mansfield, Jyoti Choudhary, James Wright, Lu Yu, Alan Melcher, Richard Vile, Matt Coffey, Martin McLaughlin, Kevin Harrington
Journal: Cancer Research (2021)

Abstract Cytoplasmic nucleic acid sensors for double-stranded (ds) RNA (RIG-I/MDA5) and DNA (cGAS-STING) are pattern recognition receptors (PRRs) key to intracellular anti-viral responses. Recent research has highlighted roles for PRR agonists, including oncolytic virotherapy agents, in anti-tumor immunotherapy. Reovirus type 3 Dearing (Rt3D) is an oncolytic dsRNA virus with limited single-agent activity in clinical studies, but potential for use in combination regimens. We sought synergistic drug-virotherapy combinations using an unbiased screening approach that highlighted the CDK4/6 inhibitor, palbociclib, as a leading hit. We found that, when combined with Rt3D, palbociclib augmented oncolytic virus-induced endoplasmic reticulum (ER) stress/unfolded protein response (UPR) signaling. Combined Rt3D-palbociclib treatment potently increased interferon signaling and endogenous retroviral transcripts. Knockdown (siRNA) studies indicated key UPR proteins and the RNA sensor, RIG-I, were essential to the phenotype observed. Mechanistically independent experiments, using canonical RIG-I agonists and the ER stress inducer (thapsigargin), confirmed cross-talk between RNA sensing and ER stress pathways that augment cancer cell death and interferon production. Combined Rt3D-palbociclib increased innate immune activation and effector function. Our findings demonstrate that UPR signaling and innate immune RNA sensor crosstalk can be exploited to enhance anti-cancer efficacy with pro-immunogenic consequences. This has implications for future clinical development of PRR agonists and oncolytic viruses, as well as broadening the therapeutic remit of CDK4/6 inhibitors to include their role as ER stress sensitizers. Citation Format: Victoria Roulstone, Joan Kyula, Richard Elliot, Christopher J. Lord, Nik Matthews, Vicki Jennings, Harriet Whittock, David Mansfield, Jyoti Choudhary, James Wright, Lu Yu, Alan Melcher, Richard Vile, Matt Coffey, Martin McLaughlin, Kevin Harrington. Mechanisms of therapeutic synergy between pattern recognition response agonists and cdk4 inhibitors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1960.
Особливості вегетативної регуляції у хворих на хронічні запальні захворювання кишечника з анемічним синдромом
Authors: Т.V. Maykova, E.V. Zygalo
Journal: GASTROENTEROLOGY (2013)

Вивчені вегетативний тонус, вегетативна реактивність і вегетативне забезпечення діяльності у 38 хворих на неспецифічний виразковий коліт (НВК) і 15 хворих на хронічний коліт (ХК) з анемічним синдромом. Групу порівняння становили 36 хворих на хронічні запальні захворювання кишечника (ХЗЗК) без анемії. Наявність анемічного синдрому у хворих на ХЗЗК супроводжується посиленням вегетативного дисбалансу в бік симпатикотонії. Зміни вегетативної реактивності проявлялися у вигляді процесів дезінтеграції між нервовим і гуморальним каналами регуляції із превалюванням гіперсимпатикотонічних реакцій у хворих на НВК й асимпатикотонічних у хворих на ХК. У хворих на ХЗЗК з анемічним синдромом змінюється структура адаптаційних реакцій — у хворих на НВК за рахунок збільшення у 2 рази реакцій напруження, а у хворих на ХК — протекторних вагусних реакцій, що свідчить про прояви дезадаптаційних процесів на фоні недостатності функціонального резерву.
The reliability, sensitivity, and specificity of Global Evaluative Assessment of Robotic Skills (GEARS) and binary scoring metrics of robotic suturing and knot tying skills in a Vesico Urethral Anastomosis (VUA) task
Authors: A. Gallagher, R. De Groote, S. Puliatti, E. Mazzone, M. Amato, G. Rosiello, A. Paludo, A. Mottrie
Journal: European Urology (2021)
Pharmacokinetics of Commonly Used Antimicrobials in Critically Ill Adults During Extracorporeal Membrane Oxygenation: A Systematic Review
Authors: Marc-Alexandre Duceppe, Salmaan Kanji, Anh Thu Do, Ni Ruo, Yiorgos Alexandros Cavayas, Martin Albert, Maxime Robert-Halabi, Samara Zavalkoff, Patrice Dupont, Gordan Samoukovic, David R. Williamson
Journal: Drugs (2021)
B cell depletion impairs vaccination-induced CD8<sup>+</sup>T cell responses in a type I interferon-dependent manner
Authors: Theresa Graalmann, Katharina Borst, Himanshu Manchanda, Lea Vaas, Matthias Bruhn, Lukas Graalmann, Mario Koster, Murielle Verboom, Michael Hallensleben, Carlos Alberto Guzmán, Gerd Sutter, Reinhold E Schmidt, Torsten Witte, Ulrich Kalinke
Journal: Annals of the Rheumatic Diseases (2021)

Objectives The monoclonal anti-CD20 antibody rituximab is frequently applied in the treatment of lymphoma as well as autoimmune diseases and confers efficient depletion of recirculating B cells. Correspondingly, B cell-depleted patients barely mount de novo antibody responses during infections or vaccinations. Therefore, efficient immune responses of B cell-depleted patients largely depend on protective T cell responses. Methods CD8 + T cell expansion was studied in rituximab-treated rheumatoid arthritis (RA) patients and B cell-deficient mice on vaccination/infection with different vaccines/pathogens. Results Rituximab-treated RA patients vaccinated with Influvac showed reduced expansion of influenza-specific CD8 + T cells when compared with healthy controls. Moreover, B cell-deficient JHT mice infected with mouse-adapted Influenza or modified vaccinia virus Ankara showed less vigorous expansion of virus-specific CD8 + T cells than wild type mice. Of note, JHT mice do not have an intrinsic impairment of CD8 + T cell expansion, since infection with vaccinia virus induced similar T cell expansion in JHT and wild type mice. Direct type I interferon receptor signalling of B cells was necessary to induce several chemokines in B cells and to support T cell help by enhancing the expression of MHC-I. Conclusions Depending on the stimulus, B cells can modulate CD8 + T cell responses. Thus, B cell depletion causes a deficiency of de novo antibody responses and affects the efficacy of cellular response including cytotoxic T cells. The choice of the appropriate vaccine to vaccinate B cell-depleted patients has to be re-evaluated in order to efficiently induce protective CD8 + T cell responses.
Vascularization of tissue engineered cartilage - Sequential in vivo MRI display functional blood circulation
Authors: Peter Apelgren, Matteo Amoroso, Karin Säljö, Mikael Montelius, Anders Lindahl, Linnea Stridh Orrhult, Paul Gatenholm, Lars Kölby
Journal: Biomaterials (2021)

Establishing functional circulation in bioengineered tissue after implantation is vital for the delivery of oxygen and nutrients to the cells. Native cartilage is avascular and thrives on diffusion, which in turn depends on proximity to circulation. Here, we investigate whether a gridded three-dimensional (3D) bioprinted construct would allow ingrowth of blood vessels and thus prove a functional concept for vascularization of bioengineered tissue. Twenty 10 × 10 × 3-mm 3Dbioprinted nanocellulose constructs containing human nasal chondrocytes or cell-free controls were subcutaneously implanted in 20 nude mice. Over the next 3 months, the mice were sequentially imaged with a 7 T small-animal MRI system, and the diffusion and perfusion parameters were analyzed. The chondrocytes survived and proliferated, and the shape of the constructs was well preserved. The diffusion coefficient was high and well preserved over time. The perfusion and diffusion patterns shown by MRI suggested that blood vessels develop over time in the 3D bioprinted constructs; the vessels were confirmed by histology and immunohistochemistry. We conclude that 3D bioprinted tissue with a gridded structure allows ingrowth of blood vessels and has the potential to be vascularized from the host. This is an essential step to take bioengineered tissue from the bench to clinical practice.
Urodynamic profile of voiding in prolapse pelvic organ patients after surgery: A systematic review
Authors: H.O.D. Santos, D.B. Lourenço, A.D. Partezani, S.B. Teles, L.S. Takemura, G.M. Andrade, F.A. Gushiken, B.A.V. Bianco, L.A.S. Rios, A. Carneiro, G.C. Lemos
Journal: European Urology (2021)
Abstract LB073: The growth inhibitory effect of paclitaxel on gefitinib-resistant non-small cell lung cancer (NSCLC) cells during the COVID-19 pandemic
Authors: Md Mohiuddin, Hideharu Kimura, Takashi Sone, Satoshi Watanabe, Hiroki Matsuoka, Keigo Saeki, Nanao Terada, Miki Abo, Kazuo Kasahara
Journal: Cancer Research (2021)

Abstract Background: Coronavirus disease 2019 (COVID-19) has posed a great challenge for the treatment of cancer patients. COVID-19 presents as a severe respiratory infection in aging individuals, including lung cancer patients. COVID-19 may be linked to the progression of aggressive lung cancer. Conversely, the side effects of chemotherapy, such as chemotherapy resistance and the acceleration of cellular senescence could worsen COVID-19. Considering the above-mentioned facts, our present work aimed to investigate the role of paclitaxel (a chemotherapy drug) in the cell proliferation, apoptosis, and cellular senescence of gefitinib-resistant NSCLC cells (PC9-MET) and to reveal the underlying mechanisms. Methods: PC9-MET cells were treated with paclitaxel for 72 h and were then evaluated by a cell viability assay, DAPI staining, Giemsa staining, apoptosis assay, ROS assay, SA-β-Gal staining, TUNEL assay and Western blotting.Results: Our results revealed that paclitaxel significantly reduced the viability of PC9-MET cells and induced morphological signs of apoptosis. The apoptotic effects of paclitaxel were observed by increased levels of cleaved caspase-3, cleaved caspase-9 and cleaved PARP. Additionally, paclitaxel increased ROS production, leading to DNA damage. Importantly, paclitaxel eliminated cellular senescence, which was observed by SA-β-Gal staining.Conclusion: In light of these findings, paclitaxel could be a promising anticancer drug and could offer a new therapeutic strategy for gefitinib-resistant NSCLC during the COVID-19 pandemic. Citation Format: Md Mohiuddin, Hideharu Kimura, Takashi Sone, Satoshi Watanabe, Hiroki Matsuoka, Keigo Saeki, Nanao Terada, Miki Abo, Kazuo Kasahara. The growth inhibitory effect of paclitaxel on gefitinib-resistant non-small cell lung cancer (NSCLC) cells during the COVID-19 pandemic [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB073.
The Presence of Philadelphia Chromosome Does Not Confer Poor Prognosis in Adult Pre-B Acute Lymphoblastic Leukemia in the Tyrosine Kinase Inhibitor Era - a Surveillance, Epidemiology, and End Results Database Analysis
Authors: Igwe John Igwe, Dongyun Yang, Merchant Akil, Noah Merin, George Yaghmour, Kevin R Kelly, Giridharan Ramsingh
Journal: Blood (2017)
Abstract 12149: Pgrn Suppresses Pressure Overload-induced Cardiac Hypertrophy and Heart Failure in Mice via Inhibiting the Activation of β-catenin
Authors: Yinghong Zhu
Journal: Circulation (2019)

Introduction: Progranulin (PGRN) is a multifunctional protein known to be involved in embryonic development, tissue repair, tumorigenesis and inflammation. Recently PGRN deficiency is known to be a...
Abstract 3183: Adrenergic signaling augments cytotoxic T-cell anti-tumor function in p53-deficient head and neck cancer
Authors: Deborah Silverman, Sara Leahey, Shamima Akhter, Tongxin Xie, Yunfei Wang, Elien Doordjuin, George Calin, Jeffrey Myers, Patrick Hwu
Journal: Cancer Research (2021)

Abstract Few advances have been made against head and neck cancers, in part because treatment efforts have focused on the epithelial component of these tumors. However, therapies targeting the microenvironment, including immune checkpoint blockade (ICB), also remain ineffective in the majority of head and neck cancers. Like some other immunotherapy-nonresponsive tumors, head and neck cancers develop a complex microenvironment heavily infiltrated by nerve fibers arising from the peripheral nervous system. Studies in multiple models have shown that the ablation of different portions of the peripheral nervous system prevents cancer development and progression. We recently showed that existing nerves sprout and undergo autonomic reprogramming to an adrenergic-like phenotype as a result of orchestrated microRNA (miRNA) shuttling from cancer cells to neurons, resulting in activation of transcriptional programs that establish new neuronal identity. Given that activated T-cell subsets express high levels of adrenergic receptors, we hypothesized that adrenergic signaling may also influence tumor-infiltrating T-cell function. We used novel murine models of OCSCC to discern the effect of adrenergic nerve signaling on immune infiltration and immunotherapy response and correlated our findings with data from patient cohorts using bulk and single-cell RNA sequencing. We found that adrenergic signaling acutely enhanced cytotoxic T-cell activity in patient-derived tumor/T-cell pairs, and we elucidated a p53-dependent mechanism underlying this effect. Ultimately, these results provide a striking contrast to the known role of adrenergic signaling in cancer development: although nerve-cancer crosstalk drives cancer aggression and progression, tumor innervation may also better enable the host immune response. Therapeutic approaches targeting this critical component of tumor biology may be useful to improve patients' survival, treatment responses, and quality of life. Citation Format: Deborah Silverman, Sara Leahey, Shamima Akhter, Tongxin Xie, Yunfei Wang, Elien Doordjuin, George Calin, Jeffrey Myers, Patrick Hwu. Adrenergic signaling augments cytotoxic T-cell anti-tumor function in p53-deficient head and neck cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 3183.
Long-term predictive value of serum PSA values obtained in clinical practice – Results from the Norwegian Prostate Cancer Consortium (NPCC)
Authors: S. Carlsson, J. Bjerner, H. Lilja, K. Aas, S.D. Fosså, C. Müller, S. Müller, A. Stensvold, O. Thomas, O.D. Røe, J. Walz, O. Bratt, J. Oldenburg
Journal: European Urology (2021)
Abstract 1313: TH1902, a docetaxel peptide-drug conjugate, shows pre-clinical efficacy in several Sortilin-positive (SORT1+) cancers
Authors: Christian Marsolais, Jean-Christophe Currie, Michel Demeule, Cyndia Charfi, Alain Larocque, Alain Zgheib, Richard Béliveau, Borhane Annabi
Journal: Cancer Research (2021)

Abstract One strategy to achieve greater selectivity of anticancer drug to cancer cells is the conjugation of cytotoxic agents to peptide ligands that selectively target receptors abundantly expressed in these tumor cells. Recently, increased expression of sortilin (SORT1), a scavenging receptor, has been observed in various cancers including breast, ovarian, endometrial, skin, colorectal and pancreatic cancers. In light of these SORT1 levels, we developed a peptide conjugation platform to target SORT1 and to increase cell selectivity and internalization of anticancer agents. Docetaxel was conjugated to a sortilin-binding proprietary peptide (TH19P01). High in vitro intracellular internalization of TH19P01 in TNBC cells was first confirmed and was reduced when SORT1 expression was silenced using siRNA or upon competition with the SORT1 ligands neurotensin and progranulin. Significant in vitro intracellular delivery of the docetaxel-TH19P01 conjugate (TH1902) was observed in SORT1+ cancer cell lines while maintaining efficient docetaxel cytotoxic mechanism. TH1902 further exerted potent anti-proliferative and anti-migratory activities when tested on TNBC-derived MDA-MB-231 cells. TH1902 also triggered faster and more potent apoptotic cell death than did docetaxel. Pre-clinical in vivo studies were performed in human SORT1+ tumor xenografts grown in mice including TNBC (MDA-MB-231 and HCC-70), melanoma (SK-MEL-28), colorectal (HT-29) and pancreatic (PANC-1) cancer models. Mice were treated with either TH1902 or docetaxel by IV bolus injections at equivalent doses of docetaxel (MTD or ¼ MTD). In all cases, TH1902 showed more potent inhibition than Docetaxel. These results strongly support future clinical development of TH1902 as novel therapeutics in SORT1+ cancers. Citation Format: Christian Marsolais, Jean-Christophe Currie, Michel Demeule, Cyndia Charfi, Alain Larocque, Alain Zgheib, Richard Béliveau, Borhane Annabi. TH1902, a docetaxel peptide-drug conjugate, shows pre-clinical efficacy in several Sortilin-positive (SORT1+) cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1313.
Abstract 2566: The potential role of licorice and its bioactive compounds in promoting a tumor preventive environment in the postmenopausal breast
Authors: Atieh Hajirahimkhan, Caitlin Howell, Shao-Nong Chen, Susan E. Clare, Guido F. Pauli, Judy L. Bolton, Birgit M. Dietz, Seema A. Khan
Journal: Cancer Research (2021)

Abstract Introduction: our purpose was to define if licorice and its main bioactive compounds can suppress aromatase expression/activity and Nrf2 dependent detoxification pathways in the postmenopausal breast. This chemopreventive potential has not previously been reported in preclinical models of high-risk postmenopausal breast. Methods: Inhibition of aromatase activity by three licorice extracts (Glycyrrhiza species), and their bioactive compounds, (liquiritigenin; LigF, isoliquiritigenin; LigC, 8-prenylapigenin; 8-PA, and licochalcone A; LicA) were evaluated fluorometrically, using aromatase supersomes. Computational docking was performed to assess the binding of the bioactive compounds to the binding pocket of aromatase crystal structure compared to the known aromatase inhibitors, letrozole (non-steroidal) and exemestane (steroidal). Using qPCR, the effects of treatments on the expression of aromatase (CYP19A1) mRNA and Nrf2 dependent detoxification enzyme NADPH:quinone oxidoreductase 1 (NQO1) in breast microstructures obtained from high risk postmenopausal women were evaluated. Results: Among the three medicinally used licorice species, Glycyrrhiza inflata (GI) showed the highest aromatase inhibitory potency (IC50 ≈ 1 µg/mL). Licorice phytoestrogens, LigF (400 nM or 0.1 µg/mL), and 8-PA (IC50 ≈ 590 nM or 0.2 µg/mL) exhibited the highest potency compared to the other tested licorice compounds. Computational docking suggested that these phytoestrogens bind to the aromatase binding pocket like the aromatase inhibitor, letrozole. This effect was not observed with non-estrogenic bioactive compounds of licorice, LigC and LicA (specific to GI). In breast microstructures obtained from high risk postmenopausal women, expression of aromatase mRNA was suppressed by GI (30%, P &amp;lt; 0.05), LigF (20%, P &amp;lt; 0.05), and LicA (45%, P &amp;lt; 0.05), while the expression of NQO1 mRNA was enhanced by LicA (200%, P &amp;lt; 0.0001). Conclusions: Licorice species, and their bioactive compounds inhibited aromatase activity in vitro. In the breast microstructures, GI, its compounds LigF and LicA suppressed aromatase expression, and LicA enhanced NQO1 induction, significantly. Further studies will further elucidate the potential of these natural products for promoting a breast tumor preventive environment in postmenopausal women. Citation Format: Atieh Hajirahimkhan, Caitlin Howell, Shao-Nong Chen, Susan E. Clare, Guido F. Pauli, Judy L. Bolton, Birgit M. Dietz, Seema A. Khan. The potential role of licorice and its bioactive compounds in promoting a tumor preventive environment in the postmenopausal breast [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2566.
Relationship between clone metrics and clinical outcome in clonal cytopenia
Authors: Anna Gallì, Gabriele Todisco, Eulalia Catamo, Cinzia Sala, Chiara Elena, Sara Pozzi, Elisa Bono, Virginia Valeria Ferretti, Ettore Rizzo, Elisabetta Molteni, Silvia Zibellini, Martina Sarchi, Emanuela Boveri, Jacqueline Ferrari, Nicolas Fiorelli, Clara Camaschella, Paolo Gasparini, Daniela Toniolo, Mario Cazzola, Luca Malcovati
Journal: Blood (2021)