tbuckley/cabot-search huggingface dataset:
Fasting-mimicking diet and markers/risk factors for aging, diabetes, cancer, and cardiovascular disease
Authors: Min Wei, Sebastian Brandhorst, Mahshid Shelehchi, Hamed Mirzaei, Chia Wei Cheng, Julia Budniak, Susan Groshen, Wendy J. Mack, Esra Guen, Stefano Di Biase, Pinchas Cohen, Todd E. Morgan, Tanya Dorff, Kurt Hong, Andreas Michalsen, Alessandro Laviano, Valter D. Longo
Journal: Science Translational Medicine (2017)

A periodic fasting diet improves markers of metabolic dysfunction, particularly in people already at risk.
Clinical Significance of PML/RAR Isoform in Patients of Acute Promyelocytic Leukemia.
Authors: Ki-Hyang Kim, Won-Sik Lee, Kyoo-Hyung Lee, Je-Hwan Lee, Seong-Jun Choi, Jung-Hee Lee, Jae-Hoo Park, Young-Joo Min, Hawk Kim, Sung-Hwa Bae, Hun-Mo Ryoo, Myung-Soo Hyun, Min-Kyung Kim, Dae-Young Zang, Hyo-Jung Kim, Jin-Seok Ahn, Chul-Won Jung, Kyeong-Won Lee, Jung-Lim Lee, Young-Don Joo
Journal: Blood (2007)
Pancreatic Cancer: Progress and Challenges in a Rapidly Moving Field
Authors: Eric A. Collisson, Kenneth P. Olive
Journal: Cancer Research (2017)

"Pancreatic Cancer: Advances in Science and Clinical Care," a Special Conference of the American Association for Cancer Research, was held in Orlando, FL, on May 12 to 15, bringing together more than 450 basic, translational, clinical, and epidemiologic pancreatic cancer researchers as well as pancreatic cancer patients, survivors, and advocates. Pancreatic cancer remains one of the great challenges in medicine, but the accelerating pace of research and early hints of clinical successes to come were palpable throughout the meeting. Prominent meeting themes included immunology and the tumor microenvironment, heterogeneity of both the epithelial and stromal compartments, personalized medicine efforts to integrate molecular information into clinical practice, new approaches to early detection, and clinical trials using a host of novel targeted therapies. Adding to the vibrant atmosphere of the meeting, a coalition of pancreatic cancer research and support foundations participated, with several innovative initiatives announced by individual organizations. We present here a summary of meeting highlights, a series of "success factors" that will benchmark the progress of the field over the next 2 years, and three challenges to the pancreatic cancer research community as it moves toward to the goal of extending patient survival. Cancer Res; 77(5); 1060-2. ©2017 AACR.
RICTOR/PI3K/mTOR as a clinically relevant driver of poor prognosis in squamous cell lung carcinoma (SqCLC): Preliminary results of prognostic outliers according to a validated clinicopathological model
Authors: S. Pilotto, M. Simbolo, I. Sperduti, S. Novello, C. Vicentini, U. Peretti, S. Pedron, M. Milella, A. Mafficini, P. Visca, M. Volante, F. Facciolo, A. Santo, M. Infante, L. Carbognin, M. Brunelli, M. Chilosi, A. Scarpa, G. Tortora, E. Bria
Journal: Annals of Oncology (2016)
Phase II study of roniciclib in combination with cisplatin/etoposide or carboplatin/etoposide as first-line therapy in subjects with extensive-disease small cell lung cancer (ED-SCLC)
Authors: M. Reck, L. Horn, S. Novello, F. Barlesi, I. Albert, E. Juhasz, J. Chung, A. Fritsch, U. Drews, M. Rutstein, A. Wagner, R. Govindan
Journal: Annals of Oncology (2016)
IMST-39. IDO1 IS PROGNOSTIC FOR GLIOBLASTOMA PATIENT SURVIVAL AND CENTRALLY CORRELATES WITH POTENTLY IMMUNOSUPPRESSIVE MEDIATORS
Authors: Lijie Zhai, Matthew Genet, Erik Ladomersky, Kristen Lauing, Meijing Wu, David Binder, Leo Kim, Jeremy Rich, Craig Horbinski, C. David James, Jeffrey Sosman, Orin Bloch, Derek Wainwright
Journal: Neuro-Oncology (2016)

Glioblastoma (GBM) is the most common and aggressive primary central nervous system cancer (CNS) in adults. Notably, biomarkers that stratify GBM patient survival are limited. Indoleamine 2,3-dioxygenase 1 (IDO1), an inducible tryptophan catabolic enzyme, has been shown to be a key mediator of tumor-induced immunosuppression in multiple settings. Here, we utilized the cancer genome atlas to investigate the correlation between IDO1 and overall survival (OS) in low grade glioma (LGG) and GBM patients, as well as non-CNS cancer. Multivariate Cox regression analysis found IDO1 mRNA levels to be an independent prognostic factor for survival, both in LGG (WHO grade II, III, P = 0.0115; HR = 1.68) and GBM (WHO grade IV, P = 0.0076; HR=1.82) patients. Interestingly, Pearson correlation analysis also identified significant associations between IDO1 and potently immunosuppressive mediators including PD-L1, PD-L2, PD-1, CTLA-4, STAT3, CD39, BTLA, Lag3, FoxP3 and FGL2, both in LGG and GBM (P < 0.01, respectively). Within GBM, IDO1 mRNA levels were higher in the cellular (1.398 ± 0.1257; P < 0.01) and necrotic zones (1.543 ± 0.1489; P < 0.01), when compared to the infiltrating (0.9303 ± 0.0786) and leading margins (0.9064 ± 0.1224). Kaplan-Meier analysis also demonstrated that high IDO1 mRNA levels predict decreased survival in patient's diagnosed with acute myeloid leukemia (P = 0.03), esophageal (P = 0.006), pancreatic (P = 0.001) and testicular (P = 0.003) cancer. These data demonstrate for the first time that, high IDO1 mRNA levels strongly correlate with decreased GBM patient survival, that its expression within different anatomic niches of GBM is independently regulated, and that these observations apply to multiple types of human cancer, providing strong rationale for further investigation into this pathogenic mediator.
A phase 1b study (SCORES) assessing safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity of durvalumab combined with AZD9150 or AZD5069 in patients with advanced solid malignancies and SCCHN
Authors: D. Hong, G. Falchook, C.E. Cook, W. Harb, P. Lyne, P. McCoon, M. Mehta, P. Mitchell, G.M. Mugundu, M. Scott, J.S. Wang
Journal: Annals of Oncology (2016)
Glucose Hypometabolism in Developmental Venous Anomaly Without Apparent Parenchymal Damage
Authors: Masamichi Imai, Mika Tanaka, Kenji Ishibashi, Aya Tokumaru, Kenji Ishii
Journal: Clinical Nuclear Medicine (2017)

Two cases of 18F-FDG PET in developmental venous anomaly (DVA) with visual impairment were examined. Plain MRI could not determine the cause of visual symptoms; a contrast-enhanced CT scan showed the existence of DVA without apparent parenchymal damage due to infarction or hemorrhage. 18F-FDG PET revealed that the hypometabolic area extended to the visual tract, thus explaining the association between the visual impairment and DVA. 18F-FDG PET is therefore a useful tool for the evaluation of symptomatic DVA.
Phase 1b/2 safety and efficacy of TAK-228 (MLN0128), plus exemestane (E) or fulvestrant (F) in postmenopausal women with ER + /HER2- metastatic breast cancer (MBC)
Authors: J. Diamond, V.F. Borges, P. Kabos, E. Krill-Jackson, R. Graham, A. Hoffman, B. Lim, D.A. Richards, M.A. Salkeni, S. Wilks, C. Patel, R. Neuwirth, M. Kneissl, F. Zohren
Journal: Annals of Oncology (2016)
Clinical Trial Units in Italy: the perception of the Clinical Research Coordinators
Authors: C. Cagnazzo, O. Nanni, S. Campora, P. Frati, R. Camisa, M. Contu, R. Sottile, G. Canzanella, L. McMahon, F. Arizio, M. Cinefra
Journal: Annals of Oncology (2016)
P08.43 Bevacizumab discontinuation and bevacizumab re-challenge in glioblastoma patients
Authors: C. Bonnet, S. Cartalat-Carel, L. Thomas, B. Joubert, D. Meyronet, A. D’Hombres, E. Jouanneau, J. Guyotat, J. Honnorat, F. Ducray
Journal: Neuro-Oncology (2016)
Broad detection of alterations predicted to confer lack of benefit from EGFR antibodies or sensitivity to targeted therapy in advanced colorectal cancer
Authors: S.J. Klempner, A. Rankin, R.L. Erlich, J. Sun, A. Grothey, M. Fakih, T.J. George,, J. Lee, J.S. Ross, P.J. Stephens, V.A. Miller, S. Ali, A.B. Schrock
Journal: Annals of Oncology (2016)
SURG-42. “GV/GA SARISSA-LANCET” AN INNOVATIVE DEVICE FOR THE IDENTIFICATION OF GLIOMA MARGINS
Authors: Georgios Vartholomatos, George Alexiou, Spyridon Voulgaris, Athanasios Kyritsis
Journal: Neuro-Oncology (2016)

Intraoperative identification and excision of glioma margins is of paramount importance since extent of resection has a prognostic significance. By modifying a cell cycle analysis protocol for flow cytometry, we have developed an extra rapid protocol that allowed a fast cell cycle analysis within 6 minutes, thus permitting the intraoperative use for tumor margins delineation. The study included thirty-one patients who underwent surgery for a presumed intracranial tumor. DNA analysis and frozen sections were performed on tumor samples and margins that were taken during surgery. There was a significant difference in G0/G1 phase, S-phase and mitoses fraction between high-grade and low-grade tumors allowing differentiation. In glioblastoma patients when we analyzed the G0/G1 phase between tumor core and perilesional tissue the difference was significant (median 58.3% versus 81.1%, p = 0.03). The difference was also significant for S-phase and mitoses fraction between tumor mass and margins (12.8 % versus 4.6%, p = 0.011 and 19.3% versus 6.8, p = 0.012). Given the above findings we propose the development of an innovative device (GV/GA Sarissa Lancet) that combines surgical aspiration and real-time analysis of surgical specimens by flow cytometry. The development of this device could be a breakthrough in intraoperative guidance for brain tumor removal. The rapid DNA analysis by flow cytometry is a promising, low-cost adjunct for intraoperative glioma excision and should be further investigated.
A phase I study of the safety and pharmacokinetics (PK) of XMT-1001 given as an intravenous (IV) infusion once every three weeks to patients with advanced solid tumors
Authors: E. Sausville, L. Garbo, G. J. Weiss, S. Anthony, D. Shkolny, A. V. Yurkovetskiy, C. Bethune, R. J. Fram
Journal: Journal of Clinical Oncology (2009)

2574 Background: XMT-1001 is a water soluble macromolecular conjugate of camptothecin (CPT). In this novel CPT pro- drug, CPT is conjugated with a 70 kDa biodegradable hydrophilic polyacetal, poly (1-hydroxymethylethylene hydroxymethylformal). XMT-1001 demonstrated an improved therapeutic window as compared with CPT and irinotecan in human tumor xenograft models, providing a compelling rationale for its clinical development. Methods: This is an open label, dose escalation study of XMT- 1001 administered as an IV infusion once every 3 weeks. The objectives of this phase I study are to determine the maximum tolerated dose and to assess safety and PK of XMT-1001. Initially 3 patients (pts) are entered at each dose level. The cohort is expanded to 6 pts if a patient experiences a dose limiting toxicity. Analyses of plasma and urine were performed for XMT-1001 (conjugated CPT), 2 major drug release products, and for unconjugated (free) CPT. Results: Thirty two pts with refractory solid tumors have received 82 cycles of XMT-1001 at 8 dose levels ranging from 1.0 to 20.5 mg CPT equivalents/m 2 . Two pts had Gr 3 infusion reactions consistent with hypersensitivity to study drug. Symptoms reversed upon discontinuation of study drug. After the introduction of new clinical trial material with an improved formulation, to date, no infusion reactions suggestive of hypersensitivity have occurred (11 patients, 22 cycles). No hemorrhagic cystitis or ≥ Gr 3 diarrhea was noted. Myelosuppression was observed in 3 pts treated at 15.4 mg CPT equiv/m 2 dose level. Stable disease was observed in 7 pts with the following tumor types and dose levels expressed in mg CPT equivalents/m 2 : NSCLC (1.0 mg/m 2 , 6 wks), ovarian (4.9 mg/m 2 , 12 wks), pancreas (4.9 mg/m 2 , 36 wks), appendiceal (7.3 mg/m 2 , 12 wks), bile duct (9.1 mg/m 2 , 18 wks), basal cell (11.6 mg/m 2 , 6 wks), and colon (15.4 mg/m 2 , 6 wks). PK demonstrates dose proportional increases in plasma levels of XMT-1001 (conjugated CPT) and confirms the formation of its expected release products. To date, levels of free CPT in urine are low. Conclusions: 1. XMT-1001 can be given safely to patients; 2. XMT-1001 has a favorable PK profile; 3. Prolonged stable disease was observed in patients with refractory tumors. [Table: see text]
DCF therapy is useful for the treatment of borderline resecatble esophageal carcinoma from early stage experience
Authors: Kazuma Kobayashi, Kantoku Nagakawa, Kengo Kanetaka, Shinichiiro Kobayashi, Takahiro Ikeda, Kosho Yamanouchi, Naomi Hayashida, Fumihiko Fujita, Tamotsu Kuroki, Susumu Eguchi
Journal: Annals of Oncology (2016)
CCL2 Chemokine Gene Expression in Lymph Nodes May Have Prognostic Value in Non-Hodgkin’s Lymphoma.
Authors: Grzegorz Mazur, Ilona Kryczek, Tomasz Wrobel, Dorota Dlubek, Aleksandra Klimczak, Emilia Jaskula, Michal Jelen, Andrzej Lange, Kazimierz Kuliczkowski
Journal: Blood (2006)
P08.68 Establishment and molecular characterization of patient derived cell lines from low grade glioma
Authors: A. Zaman
Journal: Neuro-Oncology (2017)

Background: Low Grade Gliomas (LGGs), although they are rare in incidence, usually affect younger adults (20-40 years of age) with patient survival varying between 5-15 years. The in vitro culturing of LGG and subsequent mutational profiling would be an invaluable tool for: (1) understanding mechanisms underpinning progression; (2) identifying novel diagnostic, prognostic and predictive biomarkers; and (3) identifying new treatment strategies using drug screening. Our aim is to develop and characterize patient derived LGG in vitro models through phenotypic, genetic and epigenetic analyses. Methods: Fresh LGG specimens were collected from the Prince of Wales Private Hospital, Sydney. All tumor samples were dissociated and cultured in serum free media supplemented with EGF and FGF. The minimum time to expand the cells from one passage to the next was at least 3 weeks. Successful cell lines were harvested at different passages. Molecular characterization of the tissue and cell lines were conducted using Sanger sequencing, Western blot, immunocytochemistry, short tandem repeat analyses and methylation arrays. Results: 15 IDH1 mutant LGG cell lines were developed from 34 freshly collected specimens. IDH1 mutation exclusively reverted back to wild type in all cell lines within several passages. Further molecular characterization of LGG associated genes (for example p53, ATRX, TERT, 1p 19q co-deletion) and epigenetic studies through methylation arrays of paired tumor tissue samples and cell lines enabled us to better determine the selective pressures associated with in vitro culturing of patient derived glioma cell lines. CONCLUSION: We have established and characterized LGG cell lines derived from patient tumor material and provided a unique resource to better understand LGG biology and improve targeted treatment strategies whilst also detailing the extent to which in vitro models of patient derived glioma cell lines mimic their tumor of origin.
QLIF-16. WHAT DOES THE BRAIN CANCER COMMUNITY NEED TO IMPROVE THE BRAIN CANCER JOURNEY?
Authors: Helen Bulbeck, Will Jones, Megan Hill
Journal: Neuro-Oncology (2016)

Themes that have emerged from ten years’ worth of interactions with brain tumour patients, their caregivers and healthcare professionals are the sense of isolation, lack of voice and daily challenges they face. Patients are concerned about their vitality, their identity and role limitations, mental health, emotional well-being – all are important decision factors for patients. Using online and offline channels over a period of 3 years, we created a conversation with our community, asking about their experience of their journey. Simply by joining the conversation, our community has helped us to understand more about the challenges it faces. Brain tumour patients and caregivers highlighted four main themes that would improve the quality of care for patients post surgery: A desire to know what to expect; Better mentorship, home care and personal support; The importance of understanding and accessing long term care; Increased uniformity in standard of hospital care. A granular list of needs has been identified which, once addressed, will improve the brain cancer patient’s experience of their illness. This research has given brainstrust a very clear plan of action, underpinned by the list of the community’s needs to be able to optimise care, and therefore quality of life. Aligned with the JLA Top Ten Priorities the community has the traction to make, shape and drive change so that together we can improve the quality of life and care for people living with a brain tumour and also for those who work tirelessly with this vulnerable community.
Oral rivaroxaban versus subcutaneous low molecular weight heparin treatment for venous thromboembolism in patients with upper gastrointestinal, hepatobiliary and pancreatic cancer
Authors: S. Seo, M.-H. Ryu, Y.-K. Kang, K.-P. Kim, H.-M. Chang, B.-Y. Ryoo, S.B. Kim, J.-L. Lee, S.R. Park
Journal: Annals of Oncology (2016)
Diurnal Differences in Risk of Cardiac Arrhythmias During Spontaneous Hypoglycemia in Young People With Type 1 Diabetes
Authors: Peter Novodvorsky, Alan Bernjak, Elaine Chow, Ahmed Iqbal, Lianne Sellors, Scott Williams, Robert A. Fawdry, Bhavin Parekh, Richard M. Jacques, Jefferson L.B. Marques, Paul J. Sheridan, Simon R. Heller
Journal: Diabetes Care (2017)

OBJECTIVE Hypoglycemia may exert proarrhythmogenic effects on the heart via sympathoadrenal stimulation and hypokalemia. Hypoglycemia-induced cardiac dysrhythmias are linked to the “dead-in-bed syndrome,” a rare but devastating condition. We examined the effect of nocturnal and daytime clinical hypoglycemia on electrocardiogram (ECG) in young people with type 1 diabetes. RESEARCH DESIGN AND METHODS Thirty-seven individuals with type 1 diabetes underwent 96 h of simultaneous ambulatory ECG and blinded continuous interstitial glucose monitoring (CGM) while symptomatic hypoglycemia was recorded. Frequency of arrhythmias, heart rate variability, and cardiac repolarization were measured during hypoglycemia and compared with time-matched euglycemia during night and day. RESULTS A total of 2,395 h of simultaneous ECG and CGM recordings were obtained; 159 h were designated hypoglycemia and 1,355 h euglycemia. A median duration of nocturnal hypoglycemia of 60 min (interquartile range 40–135) was longer than daytime hypoglycemia of 44 min (30–70) (P = 0.020). Only 24.1% of nocturnal and 51.0% of daytime episodes were symptomatic. Bradycardia was more frequent during nocturnal hypoglycemia compared with matched euglycemia (incident rate ratio [IRR] 6.44 [95% CI 6.26, 6.63], P &amp;lt; 0.001). During daytime hypoglycemia, bradycardia was less frequent (IRR 0.023 [95% CI 0.002, 0.26], P = 0.002) and atrial ectopics more frequent (IRR 2.29 [95% CI 1.19, 4.39], P = 0.013). Prolonged QTc, T-peak to T-end interval duration, and decreased T-wave symmetry were detected during nocturnal and daytime hypoglycemia. CONCLUSIONS Asymptomatic hypoglycemia was common. We identified differences in arrhythmic risk and cardiac repolarization during nocturnal versus daytime hypoglycemia in young adults with type 1 diabetes. Our data provide further evidence that hypoglycemia is proarrhythmogenic.
Vemurafenib (VM) in non-melanoma V600 and non-V600 BRAF mutated cancers: first results of the ACSE trial
Authors: J.-Y. Blay, J. Mazieres, D. Perol, F. Barlesi, D. Moro-Sibilot, G. Quere, J. Tredaniel, X. Troussard, S. Leboulleux, D. Malka, A. Flechon, C. Linassier, I.L. Ray-Coquard, B. Arnulf, I. Bieche, G. Ferretti, F. Nowak, M. Jimenez, N. Hoog-Labouret, A. Buzyn
Journal: Annals of Oncology (2016)
Gene Expression in Leukemic Blasts Persisting at Day 8 of Induction Therapy in Childhood ALL Displays a Common Shift towards Terminally Differentiated B Cells and a Cytoreduction-Associated Impairment of the Translational Machinery.
Authors: Peter Rhein, Stefanie Scheid, Richard Ratei, Christian Hagemeier, Karl Seeger, Renate Kirschner-Schwabe, Martin Schrappe, Rainer Spang, Wolf-Dieter Ludwig, Leonid Karawajew
Journal: Blood (2005)
Local Postsynaptic Voltage-Gated Sodium Channel Activation in Dendritic Spines of Olfactory Bulb Granule Cells
Authors: Wolfgang G. Bywalez, Dinu Patirniche, Vanessa Rupprecht, Martin Stemmler, Andreas V.M. Herz, Dénes Pálfi, Balázs Rózsa, Veronica Egger
Journal: Neuron (2016)
Molecular Determinants of Lymph Node Microenvironment Induced Host Immune Tolerance In CLL: Role for CAV1, PTPN6, and PKCβ In the Process
Authors: Christine Gilling, Amit Mittal, Vincent Nganga, Vicky Palmer, Dennis D. Weisenburger, Philip Bierman, R. Gregory Bociek, Patrick Swanson, Shantaram Joshi
Journal: Blood (2010)
STMC-09. ASSESSMENT OF TUMORIGENIC POTENTIAL OF HUMAN INDUCED PLURIPOTENT STEM CELL-DERIVED NEURAL STEM/PROGENITOR CELLS
Authors: Tsuyoshi Iida, Akio Iwanami, Jun Kohyama, Narihito Nagoshi, Morio Matsumoto, Hideyuki Okano, Masaya Nakamura
Journal: Neuro-Oncology (2016)

Previously, we demonstrated the therapeutic potential of transplanting human induced pluripotent stem cell-derived neural stem/progenitor cells (iPSC-NS/PCs) for spinal cord injury (SCI). On the other hand, we have found that some iPSC-NS/PC cell lines produce tumors resembling low grade glioma after transplantation. The purpose of this study is to investigate the genetic and epigenetic alterations in iPSC-NS/PCs that may be related to tumor pathogenesis, and to establish the evaluation criteria of iPSC-NS/PCs associated with tumorigenicity. Samples are prepared as two groups of human iPSC-NS/PCs (tumorigenic cell lines; 253G1-NS/PCs, non-tumorigenic cell lines; 201B7-NS/PCs). Infinium OmniExpress-24 and Methylation450 BeadChip were used to evaluate genome wide CNV and DNA methylation analyses of these iPSC-NS/PCs. Single nucleotide variants (SNV) were evaluated using Ion AmpliSeq Cancer Panel. Several SNVs related to cancer pathogenesis such as AKT1 were detected in 253G1-NS/PCs, whereas 201B7-NS/PC had no cancer related SNV. Several CNVs related to cancer pathogenesis were also detected in 253G1-NS/PCs, especially in the chromosome 2. Distinct differences in DNA methylation pattern were observed between 253G1-NS/PCs and 201B7-NS/PCs. In particular, the large differences of DNA methylation status were involved in several tumor suppressor genes such as PSMD5 and RBP1. Interestingly, the CNVs and DNA methylation patterns were affected not only by the difference in cell lines but also by the difference in the passage numbers. Our research group is working vigorously to pursue a clinical trial for patients with SCI within the next several years. Therefore, it is crucial to establish criteria to choose the “safe” iPSC-NS/PCs. Here, we revealed differences in their SNVs, CNVs and DNA methylation patterns, which enables us to control the quality of iPSC-NS/PCs with respect to their tumorigenicity.