tbuckley/cabot-search huggingface dataset:
NCOG-10. N-ACETYLCYSTEINE (NAC) TREATMENT CAN REVERSE CISPLATIN – INDUCED COGNITIVE DAMAGE IN RATS
Authors: Naomi Lomeli, Kaijun Di, Jennifer Czerniawski, John Guzowski, Daniela Bota
Journal: Neuro-Oncology (2016)

Chemotherapy-related cognitive impairment (CRCI) is commonly reported following the administration of chemotherapeutic agents and comprises a wide variety of neurological problems. No effective treatments for CRCI are currently available. Cisplatin is used to treat advanced ovarian and testicular cancer among other malignancies. Notably, more than 30% of advanced ovarian cancer patients develop CRCI during and after cisplatin-based chemotherapy. Here we examined the mechanisms involving cisplatin-induced hippocampal damage following cisplatin administration in a rat model and in cultured rat hippocampal neurons and neural stem/progenitor cells (NSC), and we prove that the clinically-available antioxidant, N-acetylcysteine can mitigating these damages. Adult male rats received 6 mg/kg cisplatin in the acute studies. In chronic studies, rats received 5 mg/kg cisplatin or saline injections once per week for 4 weeks. N-acetylcysteine (250 mg/kg) was administered 5 days per week during cisplatin treatment. Cognitive testing was performed 5 weeks after treatment cessation. Cisplatin-treated cultured hippocampal neurons and NSC were tested for changes in mitochondrial function, oxidative stress production, caspase-9 activation, and neuronal dendritic spine density. Acute cisplatin treatment reduced dendritic branching and spine density, induced mitochondrial degradation, and increased neural apoptosis in the hippocampus. Rats receiving the chronic cisplatin ­regimen showed impaired performance in contextual fear conditioning, context object discrimination, and novel object recognition tasks compared to controls. Cisplatin induced mitochondrial DNA damage, impaired respiratory activity, increased oxidative stress, and caspase-9 activation in cultured hippocampal neurons and NSC. N-acetylcysteine treatment prevented free radical production, ameliorated apoptotic cellular death, and partially mitigated the dendritic spine loss in cultured hippocampal neurons. N-acetylcysteine ameliorated deficits in contextual fear conditioning. Our results suggest that mitochondrial dysfunction and increased oxidative stress are involved in cisplatin-induced cognitive impairments. Therapeutic agents, such as N-acetylcysteine, may be effective in mitigating the deleterious effects of cisplatin.
A dose escalation phase 1 study of radiotherapy (RT) in combination with anti-cytotoxic-T-lymphocyte-associated antigen 4 (CTLA-4) monoclonal antibody ipilimumab (Ipi) in patients (pts) with metastatic melanoma
Authors: C. Boutros, C. Mateus, E. Routier, S. Chouaib, C. Libenciuc, M. Reigneau, I. Girault, C. Caramella, S. Hibat, S. Vagner, Y.G. Tao, N. Chaput, J. Adam, J.-C. Soria, A. Eggermont, E. Deutsch, C. Robert
Journal: Annals of Oncology (2016)
Two Year Data from a Prospective Safety Study Analyzing the Consequences of Imatinib Mesylate Inhibition of Sensitive Kinases Other Than bcr-abl in Patients with Previously Untreated Chronic Phase CML.
Authors: John Francis Seymour, Andrew Grigg, John Reynolds, Anthony P. Schwarer, Richard Hermann, Kerry McDonald Taylor, Kenneth Francis Bradstock, Anthony K. Mills, Rachel Koelmeyer, Kevin Lynch, Timothy Hughes
Journal: Blood (2006)
EXTH-25. EFFECTS OF TUMOR TREATING FIELDS (TTFIELDS) AND TEMOZOLOMIDE IN MGMT EXPRESSING AND NON-EXPRESSING PATIENT-DERIVED GLIOBLASTOMA CELLS
Authors: Paul Clark, Jordan Gaal
Journal: Neuro-Oncology (2016)

In a recent Phase 3 clinical study, addition of Tumor Treating Fields (TTFields) to temozolomide (TMZ) therapy after combined radiation/TMZ for newly diagnosed glioblastoma (GBM) significantly increased survival and progression free survival in patients with both methylated and unmethylated O-6-methylguanine-DNA methyl-transferase (MGMT) promoter status. To date, however, there have been no studies to address the potential interactions of TTFields and TMZ. Effects of TTFields and TMZ were studied in vitrousing patient-derived GBM stem-like cells (GSCs), both MGMT expressing (TMZ resistant) (12.1 GSC) and non-MGMT expressing (TMZ sensitive) (114 GSC). TTField and TMZ dose-response curves were constructed using cell proliferation and sphere-forming assays, and optimal doses used for combination TTField+TMZ studies. Dose-response curves demonstrated 50-fold increase in TMZ resistance of MGMT-expressing 12.1 GSCs (LD50≈200 µM) compared to MGMT non-expressing 114 GSCs (LD50≈4 µM). TTFields inhibited 12.1 GSC proliferation at all tested doses (50-500 kHz). At the optimal frequency of 200 kHz, TTFields effectively inhibited proliferation and tumor sphere formation of both MGMT subtypes of GSC at comparable levels (12.1 GSC: 74 ± 2.9% and 38 ± 3.2%, respectively; 114 GSC: 79 ± 3.5% and 41 ± 4.3%, respectively). In combination, TTFields (200 kHz) and TMZ (0.1-10 µM) showed an additive anti-neoplastic effect, but did not overcome TMZ resistance in the MGMT expressing 12.1 GSC line. This is the first study to report the effects of TTFields on GBM stem-like cells. The results demonstrate equal efficacy for TTFields in both types of GSCs (both +/- MGMT expression), consistent with the reported clinical benefit. The combination of TTFields and TMZ showed an additive anti-neoplastic effect; TTFields did not overcome TMZ resistance in the MGMT expressing GSC line. The expansion of such studies to include other cell lines, as well as novel combinations, may have clinical implications, particularly for patients with unmethylated MGMT GBM.
IMST-31. CMV gB/pp65 eVLPs FORMULATED WITH GM-CSF AS A THERAPEUTIC VACCINE AGAINST GBM AND MEDULLOBLASTOMA
Authors: Tanvir Ahmed, Catalina Soare, Anne-Catherine Fluckiger, Barthelemy Ontsouka, Abebaw Diress, Jasminka Bozic, Matthew Yorke, Allen Waziri, Marc Kirchmeier, David E Anderson
Journal: Neuro-Oncology (2016)

A limitation of past immunotherapeutic vaccines against glioblastoma multiforme (GBM) and medulloblastoma (MED) has been the difficulty in inducing a potent tumor-specific response, due in part to the poor immunogenicity of tumor-associated antigens, the means of formulation/delivery of the vaccine, or a combination of both. Human cytomegalovirus (CMV) is a ubiquitous, generally asymptomatic virus that is present in over 90% of GBM and MED tumors. Memory CD4+ and CD8+T cells are most frequently directed against the gB and pp65 antigens, respectively. Thus, CMV gB and pp65 represent attractive, highly immunogenic “foreign” antigen components of a vaccine against GBM and MED. A recent phase I clinical trial based on vaccination against CMV pp65 demonstrated significant improvement in overall survival of patients with GBM, and identified chemokine CCL3 as a correlate of efficacy. Enveloped virus-like particles (eVLPs) are produced after transfection of HEK 293 cells with a plasmid encoding murine leukemia virus Gag fused in-frame with CMV pp65 antigen, which gives rise to particles. Co-transfected CMV gB plasmid enables particles budding from the cell surface to incorporate the gB protein into the lipid bilayer. Surface expression of gB and internal expression of pp65 have been confirmed by CryoEM and immunogold labelling. Production and purification at the scale planned for clinical materials (50L) at a GMP-compliant manufacturer is underway. eVLPs restimulate IFN-g secreting CD4+ and CD8+ T cells in PBMCs from healthy subjects (n=8) at mean frequencies of 0.27% and 1.28%, respectively. eVLP formulation with GM-CSF augments IFN-g and CCL3 secretion in stimulated PBMCs from healthy subjects (n=4), GBM patients (n=4), and MED patients (n=4) at comparable levels among these groups. This vaccine candidate also induces CD4+ and CD8+responses in mice. A pre-IND meeting with FDA is planned for H1 2016, with anticipated phase I/IIa trial start in H1 2017.
EXTH-48. SMALL MOLECULAR TARGETING OF HOX-PBX BINDING IN GLIOBLASTOMA AS A NOVEL THERAPEUTIC TREATMENT
Authors: William Rogers, Richard Morgan, Hardev Pandha
Journal: Neuro-Oncology (2016)

The HOX genes encode a family of transcription factors that play an essential role in embryonic patterning, but are dysregulated in numerous cancers, including glioblastoma. Previous research indicates that HOX genes are overexpressed expressed in glioblastoma tumours compared to healthy astrocytes. HXR9, a small hexapeptide, was shown to have strong cytotoxic effects on glioblastoma ‘parental’ and cancer stem cells. In this study we assessed whether a new small molecular mimic (SMM) of HXR9 had similar or increased therapeutic potential. Glioblastoma cell lines were treated with varying doses of HXR9 and SMM, with cell viability determined by MTS assay. Mode of death was determined via annexin-V/7-AAD counterstain assay. RT-PCR and western blot analysis was used to determining the molecular pathway utilised by HXR9 and SMM. SMM was shown to be cytotoxic in, a dose dependent manner, in all cell lines used. Some cell lines exhibited increased sensitivity to SMM when compared to HXR9 treatment. Mode of death was determined to be apoptosis. C-Fos, a sub unit of the pro-apoptotic complex AP-1, was shown to be elevated following treatment with both HOX-PBX inhibitors. C-Fos up regulation was accompanied in all cell lines with a sharp down regulation of Bcl-2. C-Jun, an important subunit in AP-1, was shown to be unaffected by treatment, but was shown to be expressed in all cell lines prior to treatment. Results show that aberrantly expressed HOX and PBX proteins in glioblastoma can be targeted with cytotoxic effect. HXR9 and SMM treatment causes apoptosis through up regulation of C-Fos, and subsequent down regulation of Bcl-2. This mechanism may be caused by an increase of AP-1 activity, which in turn causes suppression in Bcl-2 expression.
Two-photon fluorescence microscopy of Laurdan GP domains in OK cells and rat renal brush border and basolateral membranes using polarized laser excitation.
Authors: M Levi, E Gratton, T Parasassi
Journal: Journal of the American Society of Nephrology (1997)

Tiziana Parasassi, Moshe Levi, Weiming Yu, and Enrico Gratton. Two-photon fluorescence microscopy of laurdan gp domains in biological membranes using polarized laser excitation. 41st Annual Meeting of the Biophysical Society, New Orleans, Louisiana, 1997. Biophys J. 1997; 72(2 Pt 2), Th-Pos322. Abstract Two-photon microscopy images of membranes of whole red blood cells, renal tubular cells (ORcells) and purified rat renal brush border and basolateral membranes labeled with LAURDAN show a fine texture of coexisting regions of different generalized polarization (GP) values. By measuring the relative water content of the membrane, LAURDAN GP function also monitors the lipid molecular dynamics or fluidity . We have used polarized laser excitation. In images with well defined membrane orientation, such as the erythrocyte cell sections, the association of high GP with high polarization photoselection allows the attribution of coexisting GP values to lipid domains of different dynamical properties. Due to the presence of strong fluorescence from the cytoplasmic membranes, the interpretation of the membrane GP texture in images of renal tubular cells is more complex. After masking the cytoplasmic membranes, analysis of the images of red blood cells and of renal tubular cells lead to the conclusion that the coexisting regions of different GP values, i.e., of different fluidity , have dimensions comparable to the microscope resolution in red blood cells and smaller than the microscope resolution (about 200 nm) in renal tubular cells. For their complex and mostly unknown morphology, the presence of GP domains in rat renal brush border and basolateral membranes is of difficult interpretation. Nevertheless, by plotting selected GP values, different membrane structures become apparent. (Supported by grants from NIH, VA, and CNR).
The rising incidence of stage 1 seminoma; a reflection of earlier diagnosis of germ cell cancer of the testis in last 20 years
Authors: T. Powles, J. Shamash, J. Ong, D. MacDonald, F. Kyle, C. Palmiera, H. Moller, T. Oliver
Journal: Journal of Clinical Oncology (2004)

4521 Background: The last 20 years has seen a dramatic change in outcome of treating metastatic testis cancer, coinciding with a marked increase in incidence. The reasons for this increase remain unclear. In an attempt to investigate this further, this abstract reviews pathological and clinical staging in patients registered in the Anglian Germ Cell Tumour Group data base between 1983 and 2002. Methods: Clinicians from 7 treatment centres (St Bartholomew'ss, Oldchurch, Southend, Colchester, Ipswich, Norwich and Cambridge) prospectively registered cases of testicular cancer in a central data base between 1983 and . The patients were divided into 3 time periods (1983–1988, 1989–1995, 1996–2002). The relative incidence of seminoma vs non seminoma and local vs metatatic disease were compared.The size of the stage 1 tumours were assessed and recorded from 2 of the treatment centres over the time period. Results: During the time of study, stage 1 seminoma increased significantly from 34% to 44% to 52%, while metastatic non seminoma decreased from 31% to 23% to 16% (p<0.05 for both). The relative incidence of metastatic seminoma and stage 1 non-seminoma remained unchanged. The mean age of the patients at the time of presentation of the tumour did not alter over the 20 year period. For patients with stage I disease, there was a reduction in the average size of the primary tumour (4.7 to 3.9 cms) during this period. Conclusions: The reduction in tumour size and the decreased frequency of patients with metastases could be a true product of increasing patient education about early diagnosis. The relative increase in the incidence of seminoma is an interesting observation and requires further investigation. These findings could be an artefact of patient referral data from selected centres, and needs validating by prospective cancer registrations, which is now in progress. No significant financial relationships to disclose.
The Anti-Malarial Mefloquine Demonstrates Preclinical Activity In Leukemia and Myeloma, and Is Dependent Upon Toll-Like Receptor Signaling for Its Cytotoxicity
Authors: Mahadeo A. Sukhai, Xiaoming Li, Rose Hurren, Xiaoming Wang, Skrtic Marko, Hong Sun, Marcela Gronda, Ayesh Seneviratne, Dilan Dissanayake, Sue Chow, Rod Bremner, David Hedley, Mark D. Minden, Ohashi Pamela, Aaron Schimmer
Journal: Blood (2010)
Subcutaneous Trastuzumab (scT) and metronomic oral Vinorelbine (mVRL) combination in HER2 + ve advanced breast cancer (ABC) patients (pts): a pilot evaluation of toxicity. Preliminary results of the VICTOR-4 study
Authors: F. Cicchiello, F. Riva, M.E. Cazzaniga, N. Digiacomo, D. Pelizzoni, R. Longarini, S. Capici, P. Bidoli
Journal: Annals of Oncology (2016)
A Distal Single Nucleotide Polymorphism Disrupts Development-Dependent Long-Range Transcriptional Regulation of the PU.1 Gene through the Chromatin-Remodeling Protein SATB1 in Acute Myeloid Leukemia.
Authors: Ulrich Steidl, Christian Steidl, Alexander Ebralidze, Bjoern Chapuy, Hye-Jung Han, Britta Will, Frank Rosenbauer, Annegret Becker, Katharina Wagner, Steffen Koschmieder, Susumu Kobayashi, Daniel B. Costa, Thomas Schulz, Karen B. O’Brien, Roel G.W. Verhaak, Ruud Delwel, Detlef Haase, Lorenz Trumper, Juergen Krauter, Terumi Kohwi-Shigematsu, Frank Griesinger, Daniel G. Tenen
Journal: Blood (2007)
Amplification of EGFR Wild-Type Alleles in Non–Small Cell Lung Cancer Cells Confers Acquired Resistance to Mutation-Selective EGFR Tyrosine Kinase Inhibitors
Authors: Shigenari Nukaga, Hiroyuki Yasuda, Katsuya Tsuchihara, Junko Hamamoto, Keita Masuzawa, Ichiro Kawada, Katsuhiko Naoki, Shingo Matsumoto, Sachiyo Mimaki, Shinnosuke Ikemura, Koichi Goto, Tomoko Betsuyaku, Kenzo Soejima
Journal: Cancer Research (2017)

EGFR-mutated lung cancers account for a significant subgroup of non-small cell lung cancers overall. Third-generation EGFR tyrosine kinase inhibitors (TKI) are mutation-selective inhibitors with minimal effects on wild-type EGFR. Acquired resistance develops to these agents, however, the mechanisms are as yet uncharacterized. In this study, we report that the Src-AKT pathway contributes to acquired resistance to these TKI. In addition, amplification of EGFR wild-type alleles but not mutant alleles was sufficient to confer acquired resistance. These findings underscore the importance of signals from wild-type EGFR alleles in acquiring resistance to mutant-selective EGFR-TKI. Our data provide evidence of wild-type allele-mediated resistance, a novel concept of acquired resistance in response to mutation-selective inhibitor therapy in cancer treatment. Cancer Res; 77(8); 2078-89. ©2017 AACR.
Taselisib, a selective inhibitor of PIK3CA, is highly effective on PIK3CA-mutated and HER2 amplified gastric cancer (GC) cell lines
Authors: M.M. Laterza, V. Belli, V. Ciaramella, E. Martinelli, F. Morgillo, J. Ventriglia, B. Savastano, A. petrillo, G. TIRINO, L. POMPELLA, A. Diana, M. Orditura, F. Ciardiello, F. DE VITA
Journal: Annals of Oncology (2016)
Generation of Specific Resistance Profiles in FLT3-ITD and FIP1L1-PDGFRalpha towards Specifically Acting Tyrosine Kinase Inhibitors.
Authors: Nikolas von Bubnoff, Silvia Thoene, Sivahari P. Gorantla, Jana Saenger, Christian Peschel, Justus Duyster
Journal: Blood (2006)
Aspects cliniques, endoscopiques et évolutifs de l'oesophagite disséquante chronique
Authors: H Lamouliatte, F Kikolski, L Message, F Zerbib
Journal: Endoscopy (2005)

Le diagnostic étiologique des sténoses oesophagiennes et/ou des dysphagies chroniques est parfois délicat: l'oesophagite disséquante chronique (ODC), décrite en 1997 par Ponsot et al, est de plus en plus souvent rencontrée. Le but de cette étude était de préciser les aspects cliniques, endoscopiques et évolutifs d'une série de malades avec ODC.
Immunoliposomal Delivery of Mir-29b By Targeting Tumor Antigen ROR1 Induces Epigenetic Reprograming in Human-ROR1-Expressed Mouse Model of Chronic Lymphocytic Leukemia
Authors: Chi-Ling Chiang, Frank W Frissora, Zhiliang Xie, Xiaomeng Huang, Rajeswaran Mani, Sivasubramanian Baskar, Christoph Rader, Kenneth K. Chan, Guido Marcucci, John C. Byrd, L. James Lee, Natarajan Muthusamy
Journal: Blood (2015)
Misquotation of Article
Authors: Isaiah J. Fidler
Journal: JNCI Journal of the National Cancer Institute (1976)

Journal Article Misquotation of Article Get access Isaiah J. Fidler Isaiah J. Fidler Frederick Cancer Research Center, P.D.Box B Frederick, Maryland 21701. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 56, Issue 2, February 1976, Pages 212–213, https://doi.org/10.1093/jnci/56.2.212-b Published: 01 February 1976
Clinical evaluation of the utility of a liquid biopsy (circulating tumoral cells and ctDNA) to determine the mutational profile (EGFR, KRAS, ALK, ROS1 and BRAF) in advanced NSCLC patients
Authors: L. Barrera, E. Montes-Servin, J.R. Borbolla, L. Arnold, J. Poole, V. Alexiadis, V. Singh, B. Gustafson, O. Arrieta
Journal: Annals of Oncology (2016)
Bictegravir versus dolutegravir, each with emtricitabine and tenofovir alafenamide, for initial treatment of HIV-1 infection: a randomised, double-blind, phase 2 trial
Authors: Paul E Sax, Edwin DeJesus, Gordon Crofoot, Douglas Ward, Paul Benson, Robin Dretler, Anthony Mills, Cynthia Brinson, Julie Peloquin, Xuelian Wei, Kirsten White, Andrew Cheng, Hal Martin, Erin Quirk
Journal: The Lancet HIV (2017)
Role of L1 cell adhesion molecule in gastric carcinoma.
Authors: T. Ito, Y. Kodera, C. Tanaka, N. Ohashi, G. Nakayama, M. Koike, M. Fujiwara, H. Nakanishi, A. Nakao
Journal: Journal of Clinical Oncology (2011)

56 Background: L1 cell adhesion molecule (L1) is a 200-220 kDa transmembrane glycoprotein of the immunoglobulin super family initially identified in neural cells. L1 was detected in ovarian cancer in a stage-dependent manner, was found exclusively in the invasion front of colorectal cancer, and has been considered a stem cell marker in glioma. The authors have shown that mRNA expression of L1 was a significant prognostic factor in gastric cancer (Kodera et al. Gastrointestinal Cancer Symposium 2009, abst 37). Its role in gastric cancer was further investigated. Methods: Expression of L1 was observed by immunostaining in 72 surgically resected pT4A-stage gastric cancer specimens. The association of L1 with peritoneal seeding and prognosis was elucidated. mRNA expression of L1-expressing gastric cancer cell line, KATO3, was suppressed using siRNA (KATO3 L1-). Microarray was used to indentify molecules that differ in expression between KATO3 L1- and the parental cell line. Results: L1 was scarcely stained in non-cancerous epithelial cells and intestinal metaplastic cells. L1 was detected mainly in the cell surface membrane of cancer cells in 15 of 72 specimens, more often in the intestinal type cancer. No correlation was found between L1 expression and detection of cancer cells in the peritoneal washes or development of peritoneal carcinomatosis. Nevertheless, the prognosis of L1-positive cancer was significantly inferior (p = 0.024). Prognosis was particularly poor among 6 cases where L1 was expressed in cancer cells at the invasive front (median survival time 149 days). Of 40,000 genes evaluated in the microarray, mRNA expression of 50 genes were amplified by &gt; 4-fold whereas the expression of 20 genes were attenuated to less than 1/4. Of these, expression of DYRK1A that induces apoptosis in conjunction with p53 was markedly suppressed to less than 1/8. Suppression of DYRK1A in the KATO3 L1- in comparison with the parental cell line was confirmed by RT-PCR. Conclusions: L1 affects prognosis of gastric cancer, particularly when it is expressed in cancer cells at the invasion front. Its role in the biology of gastric cancer has began to be elucidated. No significant financial relationships to disclose.
Tumor response from phase II study of combination treatment with intratumoral HF10, a replication-competent HSV-1 oncolytic virus, and ipilimumab in patients with stage IIIB, IIIC, or IV unresectable or metastatic melanoma
Authors: R. Andtbacka, M. Ross, S.S. Agarwala, M. Taylor, J. Vetto, R.I. Neves, A. Daud, H. Khong, R.S. Ungerleider, S. Welden, M. Tanaka, K. Grossmann
Journal: Annals of Oncology (2016)
Dissecting Proto-Oncogenic PIM Serine/Threonine Kinases in FLT3-ITDInduced Leukemogenesis: PIM1 Regulates CXCL12/CXCR4-Mediated Homing and Migration
Authors: Christelle Gasser, Rebekka Grundler, Laurent Brault, Alec Bullock, Tobias Dechow, Martjin Nawijn, Sabine Woetzel, Sabine Ehret, Georgina Berridge, Anke Spoo, Christine Dierks, Andrea Biondi, Stefan Knapp, Justus Duyster, Juerg Schwaller
Journal: Blood (2008)
Prognostic role of texture analysis in lung cancer treated with stereotactic ablative radiotherapy (SABR)
Authors: V. Nardone, P. Tini, L.N. Mazzoni, A.L.a. Penna, M. Biondi, L. Sebaste, T. Carfagno, E. Vanzi, G. De Otto, G. Battaglia, P. Pastina, S.F. Carbone, F. Banci Buonamici, L. Pirtoli
Journal: Annals of Oncology (2016)