tbuckley/cabot-search huggingface dataset:
Abstract 2834: Antitumor effect of AGM 130 (5’-OH-5-nitro-Indirubin oxime), a cyclin-dependent kinase inhibitor in colorectal cancer cells
Authors: Hyun-Jeong Shim, Jun-Eul Hwang, Woo-Kyun Bae, Myung-Sook Park, Hyo-Jeong Yun, Ji-Hee Lee, Sang-Hee Cho, Ik-Joo Chung
Journal: Cancer Research (2016)

Abstract The AGM 130 (5’-OH-5-nitro-Indirubin oxime) compound is derived from Indirubin, which is an ingredient of Danggui Longhui Wan and used in traditional Chinese medicine. AGM 130 can inhibit the proliferation of a variety cells by arresting the cell in the G2/M phase of the cell cycle, it is a cyclin-dependent kinase (CDK) inhibitor that has anti-proliferative activity and apoptotic effects on cancer cells. AGM 130 has improved water solubility compared to Indirubin, however still displays a low solubility in biologic fluids and a poor bioavailability. This poor water solubility limits the clinical application of AGM 130 to treat cancer. In this study, we decided to develop and evaluate a SNEDDS (self-nanoemulsifying drug delivery systems) formulation containing AGM130 for improving its solubility, dissolution rate, and bioavailability. To check the anti-proliferative effect of the AGM 130 compound on colon cancer cell line, we performed the MTT assay with the CT-26 cancer cell. We also performed cell cycle analysis, apoptotic assays and western blotting. The CT-26 cell bearing mice were treated intraperitoneally with AGM 130 loaded PPG-cRGD, 5-fluorouracil (5-FU) or AGM 130 loaded PPG-cRGD combined with 5-FU. We measured tumor volume and tumor progression of each groups. In vitro, AGM 130 showed significant anti-proliferative activity in CT-26 cell (IC 50, 1.9 μM). Cells treated with AGM 130 showed G2/M cell cycle arrest and also induced apoptosis compared to untreated cells. The western blotting analysis showed that AGM 130 inhibited CKD1/cyclin B1 and also CKD2/cyclin E. The greatest tumor regression (percentage tumor growth inhibition) was observed in the group treated with AGM 130 loaded PPG-cRGD combined with 5-FU. When 5-FU was administrated alone, the anti-tumor effect was inferior to the group treated with AGM 130 loaded PPG-cRGD alone. These results suggest that intraperitoneal administration of AGM 130 loaded PPG-cRGD inhibits tumor progression in a mouse colon cancer. Thus, AGM 130, a cyclin-dependent kinase inhibitors may provide a new therapeutic approach in the treatment of colon cancer. Citation Format: Hyun-Jeong Shim, Jun-Eul Hwang, Woo-Kyun Bae, Myung-Sook Park, Hyo-Jeong Yun, Ji-Hee Lee, Sang-Hee Cho, Ik-Joo Chung. Antitumor effect of AGM 130 (5’-OH-5-nitro-Indirubin oxime), a cyclin-dependent kinase inhibitor in colorectal cancer cells. [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 2834.
Rituximab Consolidation and Maintenance Immunotherapy Improve Outcome in B-Cell Chronic Lymphocytic Leukemia.
Authors: Giovanni Del Poeta, Maria Ilaria Del Principe, Luca Maurillo, Francesco Buccisano, Gianfranco Catalano, Adriano Venditti, Antonella Zucchetto, Alessio Pio Perrotti, Valter Gattei, Paolo de Fabritiis, Sergio Amadori
Journal: Blood (2007)
Clinical Significance of NOTCH1 mutations in Chronic Lymphocytic Leukemia.
Authors: Giovanni Del Poeta, Michele Dal Bo, Maria Ilaria Del Principe, Federico Pozzo, Dario Ragusa, Francesca Maria Rossi, Annalisa Biagi, Antonella Zucchetto, Riccardo Bomben, Massimo Degan, Antonio Bruno, Pietro Bulian, Davide Rossi, Paolo de Fabritiis, Sergio Amadori, Gianluca Gaidano, Valter Gattei
Journal: Blood (2012)
Morbidity of cytoreductive surgery with intraperitoneal chemotherapy in recurrent disease at a single institution.
Authors: H. López-Basave, F. Morales-Vasquez, J. Ruiz Molina, A. González Enciso, J. Medina, G. Calderillo Ruiz, D. Gallardo Rincon, A. Herrera Gomez
Journal: Journal of Clinical Oncology (2010)

e19686 Background: No standard effective treatment exists for peritoneal carcinomatosis (PC). Cytorreductive surgery with intraperitoneal chemotherapy (HIPEC) is a new approach for carcinomatosis. This study investigated the safety and efficacy of HIPEC of this treatment at a single institution. Methods: Between January 2007 to November 2009, 24 patients in recurrent disease with disemination peritoneal received HIPEC, after optimal surgical debulking. HIPEC was performed with close-abdomen technique. Intraperitoneal perfusion with cisplatin 25mg/m2 per litre and mitomycin C 3mg/m2 per litre; 3-4 litres for two hours in hiperthermic phase (40.5 degrees C). Patients were assessed for toxicity after IPHC administration using the NCI Common Toxicity Criteria. Results: 24 patients, 83% were female. Ten patients with ovarian cancer, nine with colorectal cancer, two with gastric cancer, two with mesothelioma peritonei and one with pseudomixoma peritonei. A mean age 55.4 years (SD 12.6; range, 26-68). No treatment-related mortality was noted. Overall morbidity was 20%. Hematologic toxicity was the most common toxicity but was of mild severity (two grade 1 thrombopenia, one grade 2 neutropenia, and one grade 3 pancytopenia). Four cases had diaphragmatic aperture and one case have bleeding in the peritonectomy site and required a new surgical procedure. The time on surgical procedures IPHC was 7.06 hours (5-9 hours). The median of bleeding was 938.88 ml (100-3700ml). The median duration of Intensive Therapy United was 1.55 days (1-4 days). Conclusions: These data suggest that aggressive cytoreductive surgery with IPHC using cisplatin and mitomycin C is safe and effective in treating peritoneal carcinomatosis. Additional studies and broader applications of this treatment are encouraged. The learning curve of combined modality treatment for peritoneal surface disease is long, and reflects patient selection and treatment expertise. No significant financial relationships to disclose.
Abstract 1176: The role of KIF3A in the suppression of canonical Wnt signaling through the KIF3A and β-arrestin complex, independent of the ciliary mechanism, in non-small cell lung cancer (NSCLC)
Authors: Minsuh Kim, Yong-Ah Suh, Ju-hee Oh, Bo Ra Lee, Joon Kim, Se Jin Jang
Journal: Cancer Research (2016)

Abstract Aberrant Wnt/β-catenin signaling is implicated in the progression of several human cancers, including non-small-cell lung cancer (NSCLC). However, mutations in Wnt/β-catenin pathway com-ponents are uncommon in NSCLC, and epigenetic mechanisms controlling the Wnt/β-catenin path-way remain unclear. Here, we show that KIF3A, a member of the kinesin-2 motor family, plays a key role in suppressing Wnt/β-catenin signaling in NSCLC cells. Knockdown of KIF3A increases both β-catenin levels and transcriptional activity, with a concomitant promotion of malignant phenotypes, such as enhanced proliferation and migration, and upregulation of stemness markers. KIF3A binds to β-arrestin, and KIF3A depletion allows β-arrestin to form a complex with DVL2 and AXIN, result-ing in β-catenin stabilization. Although primary cilia, of which the biogenesis requires KIF3A, are thought to restrain the Wnt response, pharmacological inhibition of ciliogenesis does not enhance β-catenin activity in NSCLC cells. A correlation between KIF3A loss and worse NSCLC prognosis as well as upregulation of β-catenin and Cyclin D1 further suggests that KIF3A is a suppressor of Wnt/β-catenin signaling and tumorigenesis in NSCLC. Citation Format: Minsuh Kim, Yong-Ah Suh, Ju-hee Oh, Bo Ra Lee, Joon Kim, Se Jin Jang. The role of KIF3A in the suppression of canonical Wnt signaling through the KIF3A and β-arrestin complex, independent of the ciliary mechanism, in non-small cell lung cancer (NSCLC). [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 1176.
Abstract 4111: Imaging of colon cancer-cell mitosis within liver metastasis in nude mice
Authors: Kosuke Hasegawa, Atsushi Suetsugu, Miki Nakamura, Takuro Matsumoto, Hitomi Aoki, Takahiro Kunisada, Masahito Shimizu, Robert M. Hoffman
Journal: Cancer Research (2016)

Abstract Colon cancer frequently results in metastasis to the liver, when it becomes the main cause of death. The tumor cell cycle in primary tumors and metastases are poorly understood. We developed a liver metastasis mouse model using a human colon cancer cell line (HCT-116), which expresses GFP in the nucleus and RFP in the cytoplasm (HCT-116-GFP-RFP). HCT-116 GFP-RFP (2.0 × 106) cells were injected in the spleen of a BALB/c nude mouse. The cells subsequently formed tumor colonies in the liver and retroperitoneum 28 days after cell transplantation. Using an Olympus FV1000 confocal microscope, mitosis of the dual-colored colon cancer cells could be clearly imaged in the liver and other metastases. Multi-nucleated cancer cells, in addition to a mononuclear cancer cells and their mitosis, were observed in the primary tumor and metastasis. Multi-nuclear cells were also observed in cell culture of HCT-116 GFP-RFP cells. Multi-nuclear HCT-116 cells may participate in the tumor growth in vivo. A significant difference in mitotic cells count in the primary tumor and metastasis was not observed. Citation Format: Kosuke Hasegawa, Atsushi Suetsugu, Miki Nakamura, Takuro Matsumoto, Hitomi Aoki, Takahiro Kunisada, Masahito Shimizu, Robert M. Hoffman. Imaging of colon cancer-cell mitosis within liver metastasis in nude mice. [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 4111.
β<sub>2</sub>-Adrenergic receptor agonists activate CFTR in intestinal organoids and subjects with cystic fibrosis
Authors: Lodewijk A.W. Vijftigschild, Gitte Berkers, Johanna F. Dekkers, Domenique D. Zomer-van Ommen, Elizabeth Matthes, Evelien Kruisselbrink, Annelotte Vonk, Chantal E. Hensen, Sabine Heida-Michel, Margot Geerdink, Hettie M. Janssens, Eduard A. van de Graaf, Inez Bronsveld, Karin M. de Winter-de Groot, Christof J. Majoor, Harry G.M. Heijerman, Hugo R. de Jonge, John W. Hanrahan, Cornelis K. van der Ent, Jeffrey M. Beekman
Journal: European Respiratory Journal (2016)

We hypothesized that people with cystic fibrosis (CF) who express CFTR (cystic fibrosis transmembrane conductance regulator) gene mutations associated with residual function may benefit from G-protein coupled receptor (GPCR)-targeting drugs that can activate and enhance CFTR function. We used intestinal organoids to screen a GPCR-modulating compound library and identified β 2 -adrenergic receptor agonists as the most potent inducers of CFTR function. β 2 -Agonist-induced organoid swelling correlated with the CFTR genotype, and could be induced in homozygous CFTR-F508del organoids and highly differentiated primary CF airway epithelial cells after rescue of CFTR trafficking by small molecules. The in vivo response to treatment with an oral or inhaled β 2 -agonist (salbutamol) in CF patients with residual CFTR function was evaluated in a pilot study. 10 subjects with a R117H or A455E mutation were included and showed changes in the nasal potential difference measurement after treatment with oral salbutamol, including a significant improvement of the baseline potential difference of the nasal mucosa (+6.35 mV, p&lt;0.05), suggesting that this treatment might be effective in vivo . Furthermore, plasma that was collected after oral salbutamol treatment induced CFTR activation when administered ex vivo to organoids. This proof-of-concept study suggests that organoids can be used to identify drugs that activate CFTR function in vivo and to select route of administration.
Antimicrobial Peptide LL37 and MAVS Signaling Drive Interferon-β Production by Epidermal Keratinocytes during Skin Injury
Authors: Ling-juan Zhang, George L. Sen, Nicole L. Ward, Andrew Johnston, Kimberly Chun, Yifang Chen, Christopher Adase, James A. Sanford, Nina Gao, Melanie Chensee, Emi Sato, Yi Fritz, Jaymie Baliwag, Michael R. Williams, Tissa Hata, Richard L. Gallo
Journal: Immunity (2016)
Abstract 4694: ABBV-075, a novel BET family inhibitor, disrupts critical transcription programs that drive prostate cancer growth to induce potent anti-tumor activity in vitro and in vivo
Authors: Emily J. Faivre, Denise M. Wilcox, Paul Hessler, Tamar Uziel, Paul Tapang, Terry Magoc, Daniel H. Albert, Guowei Fang, Saul Rosenberg, Keith McDaniel, Keith McDaniel, Warren Kati, Yu Shen
Journal: Cancer Research (2016)

Abstract The novel bromodomain inhibitor, ABBV-075, is being tested in a Phase I study for the treatment of solid tumors. Here, we show that potent inhibition of the BET (bromodomain and extra-terminal) family with ABBV-075 is a highly efficacious therapy in pre-clinical models of prostate cancer. The single-digit to low nanomolar anti-proliferative IC50s and potent in vivo tumor growth inhibition of ABBV-075 is mediated in part via inhibition of androgen receptor (AR)-dependent transcription. Prostate tumor incidence and CRPC clinical progression are driven by aberrant activation of the AR transcription program. Gene expression profiling and qPCR results indicate that ABBV-075 inhibited DHT-stimulated transcription of AR target genes without significant effect on AR protein expression. Further, ABBV-075 disrupted DHT-stimulated recruitment of the BET family member BRD4 to gene regulatory regions co-occupied by AR, including the well-established PSA and TMPRSS2 enhancers. Persistent BET inhibition led to the disassembly of AR occupied enhancers as measured by a reduction in AR and H3K27Ac ChIP signal and additionally downregulated enhancer RNA (eRNA) transcription. ABBV-075 displayed potent anti-proliferative activity in multiple models of resistance to the second generation anti-androgen Enzalutamide, including the F876L, L702H AR ligand binding domain mutations and the AR-V7 splicing variant. In addition to blocking the transcription activation downstream of AR, ABBV-075 is also a potent inhibitor of MYC and the TMPRSS2-ETS fusion proteins. Thus, we propose that ABBV-075 may provide a promising therapeutic option for CRPC patients who have developed resistance to second-generation anti-androgens. Citation Format: Emily J. Faivre, Denise M. Wilcox, Paul Hessler, Tamar Uziel, Paul Tapang, Terry Magoc, Daniel H. Albert, Guowei Fang, Saul Rosenberg, Keith McDaniel, Keith McDaniel, Warren Kati, Yu Shen. ABBV-075, a novel BET family inhibitor, disrupts critical transcription programs that drive prostate cancer growth to induce potent anti-tumor activity in vitro and in vivo. [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 4694.
Abstract 598: Utilization of Meditope Biosciences SnAP technology to enhance antibody internalization
Authors: Calin D. Dumitru, Elisabeth Gardiner, John Williams, Cindy Zer
Journal: Cancer Research (2016)

Abstract Therapeutic antibodies can bind to cell-surface receptors, prompting receptor internalization and effectively blocking further stimulation by the cognate receptor ligands. Receptor internalization is also exploited by antibody-drug conjugates (ADC) to promote effective delivery of cytotoxic payload to the inside of the cell. Meditope Biosciences has developed a way to use its SnAP (Site-specfi novel Antibody Platform) technology to promote enhanced internalization of antibody receptor complexes. The Meditope's SnAP technology functionally enables antibodies to bind to specific peptides, termed “meditopes’, and this property can be used to directly facilitate receptor crosslinking when meditope enabled antibodies are bound to cell surface receptors. Here we show that the affinity of the meditope enabled antibodies (trastuzumab anti-HER2 and gemtuzumab anti-CD33) for cell surface receptors results in the formation of an antibody receptor complex that can be detected by native gel electrophoresis and gel filtration. Binding of the meditope peptide to the enabled antibody does not interfere with normal antigen-antibody interaction and the formation of the peptide bound antibody:receptor complexes results in accelerated internalization of the complex, as shown by decreased surface fluorescence of Alexa 488-labeled SnAP peptides as well as by increased pHrodo-Red increased fluorescence of internalized antibodies when they reach the endosomal compartment. Finally, as a result this increased internalization, the downregulation of specific antibody mediated signaling events are much more effectively downregulated in the presence of the meditope peptide complex as compared to the antibody alone. Citation Format: Calin D. Dumitru, Elisabeth Gardiner, John Williams, Cindy Zer. Utilization of Meditope Biosciences SnAP technology to enhance antibody internalization. [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 598.
Stress Response Gene Nupr1 Alleviates Cyclosporin A Nephrotoxicity In Vivo
Authors: Pierre Galichon, Aurélien Bataille, Sophie Vandermeersch, Morgane Wetzstein, Yi-Chun Xu-Dubois, David Legouis, Alexandre Hertig, David Buob, Sandrine Placier, Naïke Bigé, Guillaume Lefevre, Chantal Jouanneau, Caroline Martin, Juan Lucio Iovanna, Eric Rondeau
Journal: Journal of the American Society of Nephrology (2016)

Acute tubular damage is a major cause of renal failure, especially at the early phase of kidney transplant when ischemia-reperfusion injury and cyclosporin A toxicity may coexist. The mechanisms of the latter are largely unknown. Using an mRNA microarray on microdissected tubules from a rat model of cyclosporin A toxicity to describe the related epithelial-specific transcriptional signature in vivo, we found that cyclosporin A induces pathways dependent on the transcription factor ATF4 and identified nuclear protein transcriptional regulator 1 (Nupr1), a stress response gene induced by ATF4, as the gene most strongly upregulated. Upon cyclosporin A treatment, Nupr1-deficient mice exhibited worse renal tubular lesions than wild-type mice. In primary cultures treated with cyclosporin A, renal tubular cells isolated from Nupr1-deficient mice exhibited more apoptosis and ATP depletion than cells from wild-type mice. Furthermore, cyclosporin A decreased protein synthesis and abolished proliferation in wild-type tubular cells, but only reduced proliferation in Nupr1-deficient cells. Compared with controls, mouse models of ischemia-reperfusion injury, urinary obstruction, and hypertension exhibited upregulated expression of renal NUPR1, and cyclosporin A induced Nupr1 expression in cultured human tubular epithelial cells. Finally, immunohistochemical analysis revealed strong expression of NUPR1 in the nuclei of renal proximal tubules of injured human kidney allografts, but not in those of stable allografts. Taken together, these results suggest that epithelial expression of NUPR1 has a protective role in response to injury after renal transplant and, presumably, in other forms of acute tubular damage.
Abstract 4778: Covalent bonding of a C8-conjugated pyrrolobenzodiazepine (PBD) monomer and dimer to a terminal guanine residue of DNA duplex and hairpin fragments
Authors: Julia Mantaj, Paul J. M. Jackson, Khondaker Miraz Jackson, David E. Thurston
Journal: Cancer Research (2016)

Abstract The pyrrolobenzodiazepines (PBDs) are a family of covalent-binding DNA-interactive minor-groove binding agents that are of growing interest due to their potential as stand-alone anticancer agents, and for their use as payloads in Antibody Drug Conjugates (ADCs). For example, one PBD Dimer, SJG-136 has reached Phase II evaluation in the clinic for ovarian and haematological cancers, and a number of PBD-based ADCs are now being evaluated in pre-clinical, Phase I and II clinical trials (e.g., SGN-CD19B, SGN-CD33A [vadastuximab talirine], SGN-CD70A, SGN-CD123A, SC16LD6.5 [Rova-T, rovalpituzumab tesirine] and ADCT-402). Until now, PBDs, which bind in the minor groove of DNA and covalently bond to a guanine residue through its C2-NH2 functional group, were thought to require a three-base-pair recognition sequence prior to covalent bonding to the central guanine (with a thermodynamic preference for binding to 5’-Pu-G-Pu-3’ sequences but a kinetic preference for 5’-Py-G-Py-3’; Pu = Purine, Py = Pyrimidine). Using HPLC/MS methodology with designed hairpin and duplex oligonucleotides, we have now demonstrated that the PBD dimer SJG-136 and the C8-conjugated PBD Monomer GWL-78 can covalently bond to a terminal guanine of DNA, with the PBD skeleton spanning only two base pairs. Control experiments with the non-C8-conjugated anthramycin along with molecular dynamics simulations suggest that the C8-substituent of a PBD monomer, or one-half of a PBD Dimer, may provide stability for the adduct. This observation highlights the importance of PBD C8-substituents, and also suggests that PBDs may bind to terminal guanines within stretches of DNA in cells, thus representing a potentially novel mechanism of action at the end of DNA strand breaks. Citation Format: Julia Mantaj, Paul J. M. Jackson, Khondaker Miraz Jackson, David E. Thurston. Covalent bonding of a C8-conjugated pyrrolobenzodiazepine (PBD) monomer and dimer to a terminal guanine residue of DNA duplex and hairpin fragments. [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 4778.
Re: Prediction of Axillary Lymph Node Status in Breast Cancer Patients by Use of Prognostic Indicators
Authors: S. MENARD, N. CASCINELLI, F. RILKE, M. I. COLNAGHI
Journal: JNCI Journal of the National Cancer Institute (1995)

Andersson informs us that he basically agrees with the point of view of Wakeford and Tawn.Andersson and his group had considered performing the molecular genetic analysis to determine if any mutations were obvious in the retinoblastoma case they referred to in their recent report.They state that, unfortunately, no histopathological specimens were available to them.