tbuckley/cabot-search huggingface dataset:
Abstract 5104: Isorhapontigenin (ISO) inhibits cancer invasion by enhancing FOXO1 transcription through targeting STAT1 phosphorylation at Tyr701
Authors: Lei Xue, Guosong Jiang, Jingxia Li, Chuanshu Huang
Journal: Cancer Research (2015)

Abstract Muscle invasion of bladder cancer can progress to life threatening metastases. Isorhapontigenin (ISO) is a novel derivative of stilbene that isolated from a Chinese herb Gnetum cleistostachyum, which has been used for centuries as treatment for several cancers including bladder cancer. However, nothing is known whether ISO possesses an inhibitory effect on invasion in human cancers. Here, we found that 10 to 20 mmol/L of ISO, which were relevant to in vivo study, inhibited human bladder cancer cell invasion accompanied by up-regulation of the forkhead box class O1 (FOXO1) mRNA transcription. Accordingly, FOXO1 was significantly down-regulated in invasive human bladder cancer tissues, and forced expression of FOXO1 specifically suppressed invasion of human bladder cancer cells. Moreover, knockdown of FOXO1 expression abolished the ISO inhibition of invasion. Further studies showed that increased FOXO1 transcription was accompanied by reduction of STAT1 phosphorylation at Tyr701, and repressing STAT1 phosophorylation by the overexpression of dominant negative STAT1 could mimic the effect of ISO treatment on FOXO1 transcription, while the mutation of STAT1's binding site in the FOXO1 promoter profoundly impaired ISO-induced up-regulation of FOXO1 transcription. Furthermore, this study revealed that metalloproteinase-2 (MMP-2) was a FOXO1 downstream effector mediating its effect on bladder cancer invasion. These findings not only provide a novel insight into the understanding of underlying mechanism of bladder cancer's propensity to invasion, but also identify a new role and mechanisms underlying the natural compound ISO that specifically suppresses such invasion through targeting the STAT1-FOXO1-MMP2 axis. Citation Format: Lei Xue, Guosong Jiang, Jingxia Li, Chuanshu Huang. Isorhapontigenin (ISO) inhibits cancer invasion by enhancing FOXO1 transcription through targeting STAT1 phosphorylation at Tyr701. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5104. doi:10.1158/1538-7445.AM2015-5104
Prognostic factors in patients with advanced gastric cancer treated with cisplatin plus fluoropyrimidine
Authors: Naoki Fukuda, Yoshihito Ohhara, Yuya Hirata, Fumiaki Yokoyama, Yoko Ishibashi, Nozomu Sugai, Hideyuki Seki, Jun Fujita, Junichi Suzuki
Journal: Annals of Oncology (2015)
Abstract 3803: Transcriptome analysis of MCF7 breast cancer cells with different expression profile of PAR-4 (prostate apoptosis response-4) in the presence and absence of docetaxel
Authors: Simone A. de Bessa Garcia, Ana C. Pavanelli, Natalia C. Melo, Maria A. Nagai
Journal: Cancer Research (2015)

Abstract The ability of cancer cells to evade apoptosis is one of the essential alterations in cell physiology that dictate tumor growth and impact chemo- and radio-resistance. Experimental evidence indicates that protein kinase C apoptosis WT1 regulator (PAWR) gene, also known as prostate apoptosis response-4 (PAR-4), plays an important role in tumor cell survival, and may be considered a candidate for tumor cell selective therapy. This selective ability of Par-4 to directly cause apoptosis in most cancer cells is associated with its nuclear translocation and its phosphorylation state. PAR-4 acts in both intrinsic and extrinsic apoptotic pathways. In the present study, we sought to evaluate the effects of PAR-4 on the expression profile of MCF7 breast cancer cells in the presence and absence of docetaxel. MCF7 breast cancer cells were transfected with the expression vector pCMV6-PAR-4 or pCMV6-Neo. Real time PCR, western blot and immunofluorescence were used to characterize the clones over-expressing PAR-4. Using cDNA microarray analysis, we evaluated the transcriptome changes in the comparison between MCF7 cells with increased expression of PAR-4 and the control cells before and after docetaxel treatment. Several differentially expressed genes were identified as potentially involved in PAR-4-mediated chemosensitivity to docetaxel. Using the Ingenuity program, several gene networks were generated from the differentially expressed genes, including many genes direct and indirectly involved in the canonical WNT (Wingless-Type MMTV Integration 1) signaling pathway. The Wnt Signaling Pathway Human RT2 Profiler PCR Array was used to validate the differentially expressed genes involved in the Wnt pathway identified in MCF-7 cells with differences of Par-4 expression before and after exposure to docetaxel. The validation results confirm the data observed by cDNA microarray showing that the increase in PAR-4 expression modulates the expression of many genes involved in the Wnt signaling pathway in MCF7 breast cells. The results generated could be of particular interest for the understanding the action of PAR-4 in chemosensitivity, especially to increase the specificity and effectiveness of drug treatment and overcoming resistance to chemotherapy. Supported by FAPESP and CNPq. Citation Format: Simone A. de Bessa Garcia, Ana C. Pavanelli, Natalia C. Melo, Maria A. Nagai. Transcriptome analysis of MCF7 breast cancer cells with different expression profile of PAR-4 (prostate apoptosis response-4) in the presence and absence of docetaxel. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3803. doi:10.1158/1538-7445.AM2015-3803
Down-Modulation of Shp1 and Hsp70 Provides a Survival Advantage to the Ph+ Cells of CML Patients Additive to That Related to the Oncogenic BCR/ABL Protein and May Account for Resistance to Ima Treatment.
Authors: Nicola Esposito, Fabrizio Quarantelli, Barbara Izzo, Giada Muccioli Casadei, Luigia Luciano, Giuseppe Saglio, Junia V. Melo, Thea Kalebic, Giovanni Martinelli, Fabrizio Pane
Journal: Blood (2007)
What Predicts Success for a New Composite Endpoint: Graft–versus-Host Disease-Free and Relapse-Free Survival (GRFS) after Allogeneic Hematopoietic Cell Transplantation?
Authors: Shernan G. Holtan, Todd E. DeFor, Aleksandr Lazaryan, Nelli Bejanyan, Mukta Arora, Bruce R. Blazar, Margaret L. MacMillan, Daniel J. Weisdorf
Journal: Blood (2014)
Platelet Apoptosis and Agonist Mediated Activation In Myelodysplastic Syndromes
Authors: Nora V. Butta, Raquel de Paz, Mónica Martín Salces, Ihosvany Fernández Bello, Elena G. Arias Salgado, Mayte Álvarez Román, Isabel Rivas, Ana Rodríguez de la Rúa, Víctor Jiménez-Yuste
Journal: Blood (2010)
BMET-33. MORBIDITY AND MORTALITY OF OMMAYA RESERVOIR PLACEMENT FOR INTRAVENTRICULAR CHEMOTHERAPY
Authors: Jonathan C. Lau, David R. Macdonald, Joseph Megyesi
Journal: Neuro-Oncology (2016)

In 1963, a Pakistani neurosurgeon by the name of Ayub Ommaya proposed a surgical technique for subcutaneous reservoir and pump placement to allow access to intraventricular cerebrospinal fluid (CSF). Currently, the most common indication for Ommaya reservoir insertion in adults is for patients with hematologic or leptomeningeal disorders. We wished to examine short-and-long-term outcomes in patients treated with Ommaya reservoirs at our institution. We retrospectively evaluated all operative cases of Ommaya reservoir insertion from 2000-2014 by the senior author (JFM). Patient demographic data, surgical outcomes, peri-operative complications, and long-term outcomes were collected. 28 patients underwent image-guided Ommaya reservoir insertion by the senior author (JFM) over the study period (43.3 +/- 17.3 years; 35.7% female). The most common indications for placement were acute lymphoblastic leukemia, diffuse large B-cell lymphoma, and leptomeningeal carcinomatosis. There were two complications: one asymptomatic peri-operative intracranial hemorrhage (3.6%), and one early infection (3.6%) requiring catheter removal and intravenous antibiotics. All catheters were accurately placed (100% success rate). Data collection for long-term outcome is currently underway. Our findings suggest minimal short-term morbidity with improved accuracy and decreased complications using an image-guided approach compared with a traditional approach. There were no peri-operative deaths in our series. Our results support routine use of intra-operative image guidance for proximal catheter insertion in elective Ommaya reservoir placement for intraventricular chemotherapy.
Phase II study of capecitabine and irinotecan as first-line treatment in metastatic colorectal cancer: First trial of the Brazilian Oncology Consortium (BOC-CRC 001)
Authors: C. H. Barrios, F. Viola, L. Camillo-Coura, R. F. Silva, A. Del Giglio, C. Mathias
Journal: Journal of Clinical Oncology (2004)

3725 Background: Capecitabine and Irinotecan have different mechanisms of action and are both active in colorectal cancer (CRC). Capecitabine is activated by intratumoral thymidine phosphorylase and this enzyme may be up-regulated by irinotecan. The combination of these two drugs is tested in this multicenter phase II trial, the first of a new cooperative group: Brazilian Oncology Consortium (BOC CRC-001). Methods: A total of 37 pts with measurable metastatic CRC were included. 21men (57%) and 16 women (43%); median age 53.6 (23–74). Most pts were ECOG PS 0 29/35 (82%), 5% were PS 2. Tumor differentiation was GII in 75% and GIII/IV in 14% of the cases. Liver involvement was present in 65% of the pts. 13/37 (35%) of the pts had received previous adjuvant 5FU/LV. The treatment regimen included Capecitabine 1000mg/m2 PO twice daily for 14 days and Irinotecan 75mg/m2 IVover 90 min d1and 8. Cycles repeated every 3 weeks. Patients >65 years old received lower doses of both agents (750/60) and were required to have PS ECOG 0–1. Results: A total of 222 chemotherapy cycles were delivered, median number: 6 (1–17). All pts were evaluable for toxicity. Most common AE (>5%) were diarrhea (15%), nausea (11%) and vomiting (7%). Only 5% of the AE were severe and only 11/37 (22%) pts required dose adjustments due to AE. All pts were available for response: RR 15/37 (40.5%) (95 CI 24–56%). Only 4/13 pts previously treated with adjuvant 5FU/LV responded (30.7%) while 11/24 pts without previous treatment responded (45.8%). 18/37 (48%) of the patients have died. Median survival was 363 days. Conclusions: Capecitabine and Irinotecan in this schedule are well tolerated, convenient and have activity in metastatic CRC. Patients previously treated with adjuvant chemotherapy may have a lower response rate. An independent radiology review is being performed to confirm the results. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis Lilly Roche Aventis Aventis
Clinical Patho-physiological Studies on the Effect of Low Oxygen Gas Inhalation on the Renal Electrolyte Metabolism in Healthy Subjects, Patients with Hypertension and those with Nephrosclerosis
Authors: Akira Kusaka
Journal: Circulation (1966)

Reports on renal electrolyte metabolism at rest in healthy subjects and hypertension have been found since the initiation of renal clearance methods and renal vein catheterization. However, little results are available on the effect of low oxygen gas inhalation on it. The effects of low oxygen gas inhalation on visceral circulation-metabolism in several main organs have been studied at our department. The author attempted to examine its effect on renal electrolyte (Na and K) metabolism. Methods and Subjects Methods : Renal electrolyte income and out-lay were determined at room air inhalation, subsequently during 10% O2 inhalation for 20 minutes by standard renal clearance under simultaneous renal vein catheterization. Sodium and potassium were determined by using flame photometer, Lange 11 type. Subjects: 1) Healthy subjects (Group I, 6 cases): blood pressure below 140/90mmHg, albuminuria(-), PSP (15min.) 25 to 35% ; K.W. 0 degree. 2) Pulmonary tuberculosis (Group II, 4 cases) : blood pressure below 140/90mmHg; albuminuria (-), PSP (15min.) 25 to 35% ; K.W. 0 to 1 degree. 3) Essential hypertension (Group III, 7 cases) : blood pressure 168∼184/95∼136 mmHg. ; albuminuria (-), PSP (15min.) 20 to 30% ; K.W. IIa to IIb degree. 4) Nephrosclerosis (Group IV, 4 cases) : blood pressure 170∼194/96∼106 mm Hg; albuminuria (-); PSP (15min.) 15 to 17% ; K.W. IIb to III degree; 21 cases in total. In the following, the results are described in the above mentioned order, with the means for each group. Results A. Renal electrolyte metabolism during room air inhalation. 1) Plasma level (mEq/L). Na: 139.7, 136.8, 136.7, 137.8. K: 3.6, 3.6, 3.5, 3.1. 2) Filtration amount (μEq/min). Na: 17110, 15452, 15624, 11567. K: 445, 401, 403, 267. 3) Reabsorption amount (μEq/min). Na: 16544, 15143, 14927, 11287. K: 367, 249, 313, 183. 4) Urinary excretion (μEq/min). Na: 582, 309, 691, 285. K, 53, 53, 75, 65. 5) Renal clearance (cc/min). CNa: 4.2, 2.3, 5.1, 2.4. CK: 14.6, 14.9, 21.9, 23.7. 6) CK/CN. : 3.5, 8.7, 4.5, 10.1.
Abstract 3547: Systemically delivered human telomerase reverse transcriptase (hTERT)-targeting p53-laden adenovirus shows strong antitumor effects in intrahepatic Hep3B xenograft mouse model
Authors: Won Sup Lee, Hye Lim Kang, Arulkumar Nagappan, Jeong Won Yun, GonSup Kim, Soon Chan Hong, Sang-Jin Lee, In-Hoo Kim
Journal: Cancer Research (2015)

Abstract Human telomerase reverse transcriptase (hTERT) RNA and p53 tumour suppressor were previously suggested as useful targets for cancer gene therapy. In this study, we investigated the effects of systemically delivered adenoviruses harboring trans-splicing ribozyme that could target hTERT and induce p53 transcript in targeted cancer cells in vivo using mice with Hep3B human hepatocellular carcinoma cells that metastasized to the liver. We observed that intravenous injection of this virus (0.5 X1011 Virus) produced efficient regression of Hep 3B tumor metastasized nodules. Next we performed in vitro study to know whether it has a synergistic effects with CDDP, we observed that CDDP (2.5 ug/ml) increased cytotoxic effects in vitro given with the virus (10 MOI), but in vivo study revealed that addition of CDDP or arsenic hexoxide (As4O6) did not improve the therapeutic efficacy of the virus treatment. Next we performed toxicity test with 4 doses (0.5 X1011, 1 X1011, 2 X1011, and 5 X1011, Virus), which revealed that there were no toxic death, but 2-4 fold increased in AST and ALT with no changes in bilirubin, BUN, Creatinine levels. In conclusion, this study demonstrates that the adenoviruses harboring trans-splicing ribozyme targeting hTERT and inducing p53 transcript represents a safe and promising cancer treatment for hepatocellular carcinoma. [This study was supported by a grant from the National R&amp;D Program for Cancer Control, Ministry for Health, Welfare &amp; Family Affairs, Republic of Korea. (0820050), and National Research Foundation of Korea (NRF) grant funded by the Korea government(MEST) (20120002631).] Keywords: Adenovirus, trans-splicing ribozyme, p53 tumour suppressor, Human Telomerase Reverse Transcriptase, cancer Citation Format: Won Sup Lee, Hye Lim Kang, Arulkumar Nagappan, Jeong Won Yun, GonSup Kim, Soon Chan Hong, Sang-Jin Lee, In-Hoo Kim. Systemically delivered human telomerase reverse transcriptase (hTERT)-targeting p53-laden adenovirus shows strong antitumor effects in intrahepatic Hep3B xenograft mouse model. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3547. doi:10.1158/1538-7445.AM2015-3547
Outcome of BONE Marrow Transplantation in Congenital Diskeratosis: Preliminary DATA from the European Group for BONE Marrow Transplantation (EBMT)
Authors: Francesca Fioredda, Elisabeth T Korthof, Simona Iacobelli, Cora Knol, Joan H Veelken, Paul Veys, Ayami Yoshimi, Karin Mellegren, Franca Fagioli, Marco Zecca, Alexey Maschan, Tracey O'Brien, Miguel Angel Diaz, Owen Smith, Gerard Socie, de la Fuente Josue, Reuven Or, Carlo Dufour
Journal: Blood (2015)
110. Safety and Antitumor Effect of Oncolytic and Helper-Dependent Adenoviruses Expressing Interleukin-12 Variants in a Hamster Pancreatic Cancer Model
Authors: Joanna Poutou, Maria Bunuales, Manuela Gonzalez, Eva Garcia-Aragoncillo, Jose I. Quetglas, Raquel Casado, Carlos Bravo-Perez, Pilar Alzuguren, Ruben Hernandez-Alcoceba
Journal: Molecular Therapy (2015)

Gene transfer of potent immunostimulatory cytokines such as interleukin-12 (IL-12) is a potential treatment for advanced cancer. Different vectors and IL-12 modifications have been developed to avoid side effects associated with high serum levels of the cytokine, while preserving its antitumor properties. Here we have evaluated two alternative strategies using the Syrian hamster as a model for pancreatic cancer metastatic to the liver. Local administration of an oncolytic adenovirus (OAV) expressing a single-chain version of IL-12 caused transient, very intense elevations of IL-12 in serum, resulting in severe toxicity at sub-therapeutic doses. Anchoring IL-12 to the membrane of infected cells by fusion with the transmembrane domain of CD4 reduced systemic exposure to IL-12 and increased the tolerance to the OAV. However, only a modest increase in the therapeutic range was achieved because antitumor potency was also reduced. In contrast, systemic administration of a helper-dependent adenoviral vector (HDAd) equipped with a Mifepristone-inducible expression system allowed sustained and controlled IL-12 production from the liver. This treatment was well-tolerated and inhibited the progression of hepatic metastases. We conclude that HDAds are safer than OAVs for the delivery of IL-12, and are promising vectors for immunogene therapy approaches against pancreatic cancer.
Utility of CD81 Flow Cytometry (FC) Assessment In Diagnostic Evaluation of Plasma Cell (PC) Disorders
Authors: Haris Kartsios, Vassilios Papadopoulos, Smaragda Effraimidou, Kyriaki Kokoviadou, Anastasia Spyrou, Eleni Gatsa, Anna Kioumi, Ioannis Korantzis
Journal: Blood (2010)
Abstract 5546: A natural alkaloid, berberine, as a novel transcriptional repressor of RET proto-oncogene in medullary thyroid carcinoma
Authors: Daekyu Sun, Vishnu Kumarasamy
Journal: Cancer Research (2015)

Abstract The development of several medullary thyroid carcinomas is strongly associated with the gain-of-function mutation of the RET proto-oncogene, which encodes a receptor tyrosine kinase, so that the RET protein has been regarded as a potential therapeutic target for the treatment of progressive and advanced MTC. In our study we have explored a new strategy to repress the transcription of the RET proto-oncogene in MTC using small molecules. Interestingly, we found that a natural product berberine inhibits the RET gene transcription by specifically targeting the promoter region of this gene, thereby reducing the RET protein expression in MTC TT cells. The down-regulation of RET with berberine also results in the suppression of cell proliferation through cell cycle arrest and activation of apoptosis in TT cells. Overall, our results strongly suggest that berberine stabilizes G-quadruplexes formed from the G-rich sequence present on the promoter region of this gene and the stabilization of this structure play a critical role in mediating the repressive effect of berberine on RET transcription. Citation Format: Daekyu Sun, Vishnu Kumarasamy. A natural alkaloid, berberine, as a novel transcriptional repressor of RET proto-oncogene in medullary thyroid carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5546. doi:10.1158/1538-7445.AM2015-5546
A Phase I Trial of the Intravenous (IV) Hsp90 Inhibitor 17-DMAG (alvespimycin) in Patients (pts) with Relapsed Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)
Authors: Kami Maddocks, Erin K Hertlein, Joseph M. Flynn, Leslie A Andritsos, Amy J. Wagner, Timothy L. Chen, Mitch A. Phelps, Michael R. Grever, Amy J. Johnson, John C. Byrd, Jeffrey A. Jones
Journal: Blood (2012)
Abstract SY45-01: Defining the origin of tumor heterogeneity in epithelial cancers
Authors: Cedric Blanpain
Journal: Cancer Research (2015)

Abstract Different theories have been proposed to explain tumor heterogeneity including the cancer cell of origin. Here, we developed genetically engineered mouse models allowing lineage tracing together with oncogenic activation in different cell lineages, and assessed whether the cancer cell of origin controls tumor heterogeneity. Mouse skin squamous cell carcinoma (SCC) arising from the interfollicular epidermis (IFE) are all well-differentiated SCCs. In contrast, tumors that arise from the same oncogenic hits in the hair follicle (HF) lineages displayed considerable heterogeneity ranging from well-differentiated SCCs to fibroblastic-like cancers exhibiting epithelial to mesenchymal transition (EMT) features. I will discuss further evidence that the cancer cell of origin controls EMT-related tumor heterogeneity and the underlying molecular mechanisms that promote multilineage differentiation, tumor propagation, EMT and metastasis in primary skin SCCs. Breast cancer is the most frequent cancer in women and consists of heterogeneous types of tumors that are classified into different histological and molecular subtypes. PIK3CA and p53 are the two most frequently mutated genes and are associated with different types of human breast cancers. I will present new results uncovering the cellular origin of mammary tumors. These results have important implications for our understanding of the mechanisms controlling tumor heterogeneity and the development of new strategies to block tumor initiation. This work is supported by the WELBIO, the FNRS, the Fondation Bettencourt-Schuler and the Fondation Baillet-Latour. Citation Format: Cedric Blanpain. Defining the origin of tumor heterogeneity in epithelial cancers. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr SY45-01. doi:10.1158/1538-7445.AM2015-SY45-01
Dose Dense, High Intensity Therapy in Newly Diagnosed Elderly Patients with Acute Myeloid Leukemia Using Gemtuzumab Ozogamicin (Mylotarg™) and High Dose Cytarabine (HiDAC).
Authors: Arati V. Rao, David A. Rizzieri, Joseph O. Moore, Carlos DeCastro, Amy P. Abernethy, McLean Jordan, Patty Davis, Emily Edmonds, Jon P. Gockerman
Journal: Blood (2004)