tbuckley/cabot-search huggingface dataset:
OS7.1 Identification and characterization of brain metastasis initiating cells
Authors: Y. Liao, A. S. Berghoff, M. Osswald, A. Ilhan-Mutlu, B. Gil, C. Thome, M. Ratliff, P. Steeg, W. Wick, F. Winkler
Journal: Neuro-Oncology (2016)

Brain metastases (BM) are an increasing challenge. Insight in the pathology of the brain metastatic cascade, and in particular in the characteristics of the BM initiating cells can help to identify new treatment targets. PHK26 membrane dye was used in stably GFP expressing human breast cancer to differentiate slow from fast cycling cells by membrane signal intensity changes using multiphoton laser scanning microscopy, both in vitro and in vivo. The heterogeneous population of fast and slow cycling cells as well as resting cells was injected intracardially and followed with in vivo repetitive multiphoton laser microcopy via a chronic intracranial window. Here, slow cycling cells, representing only 16% of the entire cell population, were the only ones that mastered all steps of the brain metastatic cascade (0% marcometastasis formation after intravascular arrest of fast cycling cells vs. 6.15% marcometastasis formation after intravascular arrest of slow cycling cells; p<0.001), namely intravascular arrest, extravasation, perivascular survival, and marcometastasis outgrowth. These slow cycling cells showed a high overlap with established markers for tumor stem-like cells, like Oct4/Sox2, Notch and WNT, and also (but less) with low 26S proteasome activity. Illumina gene expression profiling of slow versus fast cycling JIMT1 breast cancer cells revealed up-regulation of N-Myc down regulated gene (NDGR1). Knock down of NDRG1 resulted in complete inhibition of BM formation by preventing successful colonization of the perivascular niche. In conclusion, slow cycling cells resemble the population of BM initiating cells. Increased NDRG1 expression is a characteristic of slow cycling cells, and is a pivotal molecular precondition for successful BM formation that might serve as a potential target for BM prevention or treatment.
Prognostic factors in preoperative radiotherapy for locally advanced rectal cancer
Authors: J. Prausova, R. Lohynska, B. Malinova, J. Novotny
Journal: Journal of Clinical Oncology (2004)

3647 Background: Preoperative radiotherapy and chemoradiotherapy lower the risk of local recurrence and improves survival in stage II and III rectal cancer. Methods: Retrospective clinical study was performed to evaluate 165 patients (33% women and 67% men) with locally advanced rectal adenocarcinoma treated with preoperative radiotherapy or chemoradiotherapy in the period 1998–2002. Tumor extent was evaluated on CT or MRI or TRUS and tumor biopsy was taken during colonoscopy. The median follow up is 21 month. All patients received preoperative external beam radiation to primary tumor, adjacent lymphnodes and presacral region. CT localisation of target volume was used for 3D radiotherapy treatment planning. Patients were treated using linear accelerator with irregularly shaped three-field or four-field technique. Accelerated regimen (25 Gy/5 fraction/1 week) was performed in 14% of patients especially in year 1998–2000 and normofractionated regimen (40–50 Gy/20–25 fractions/4–5 weeks) was performed in 86 % of patients. Chemoradiotherapy with 5-FU was carried out in 22% of patients. Results: Radical resection underwent 85% of patients, inoperable tumor persisted in 7% and distant metastases were detected peroperatively in 8%. The overall survival (OS) rate at 2-years is 84% and at 5-years 60% following radical resection. The important prognostic factor affecting survival are postradiotherapy determined pathological stage (p=0,005), postradiotherapy assessed tumor grade (p< 0,001) and angioinvasion and/or perineural spread (p=0,023). Prognostic factors for DFS were identical with those for OS. Higher local recurrence rate was associated in preradiotherapy assessed T4 tumor (p=0,048) and in presence of angioinvasion and/or perineural spread (0,049). No statistically significant association was found according to age, tumor location, preradiotherapy biopsy evaluated histology grading and tumor downstaging for survival and the local recurrence rate. Conclusions: The best survival rates are obtained in patients with postradiotherapy grade 1 tumors, tumors without angioinvasion and perineural spread and complete remission after preoperative RT. No significant financial relationships to disclose.
MPTH-19. GLIOMA CHARACTERIZATION USING THE NOVEL BIOMARKER ACID CERAMIDASE
Authors: Mona M. Al-Gizawiy, Ninh B. Doan, Kathleen M. Schmainda, Wade M. Mueller, Jennifer M. Connelly, Shama P. Mirza
Journal: Neuro-Oncology (2016)

Acid ceramidase (ASAH1) plays an important role in the production of sphingosine-1-phosphate (S1P), a known tumor promotor. While S1P was shown to stimulate invasiveness of glioblastoma (GBM) cells in vitro, the exact role of ASAH1 in glioma biology still needs to be established. To our knowledge, this is the first use of ASAH1 to characterize gliomas by grade and type. All studies were conducted with IRB approval. Tissue specimens of 19 consented adult patients who previously underwent therapeutic brain tumor resection were submitted for ASAH1 immunohistochemistry (IHC). Photomicrographs of stained tissues were graded blindly using the Allred scoring system before scores were matched with the individual pathological diagnoses. Glioma tissues from all specimens stained positive for ASAH1, but to varying degrees. Mean Allred scores were lower (AS=5) in Grade II oligodendrogliomas and mixed oligoastrocytomas vs. pure astrocytomas (AS=7). Similarly, mean Allred scores were lower in conventional GBMs (AS=6) compared to GBMs with oligodendroglial component (mixed GBM, AS=7). While it is possible that ASAH1 is naturally overexpressed in astrocytomas, it is more likely our IHC scores reflect the dense cellularity of these tumors. This is consistent with our previous advanced MR imaging findings where the ADC of pure astrocytomas was significantly lower than that of oligodendrogliomas and mixed tumors, and mixed GBMs had a significantly lower ADC than conventional ones. The high IHC scores (AS=7) seen in recurrent GBM samples are likely due to overexpression of ASAH1 following radiation therapy. Our results support a biological distinction between astrocytomas and oligodendrogliomas, and a biological agreement between oligodendrogliomas and oligoastrocytomas, corroborating previous findings that mixed gliomas may not represent a separate glioma group, but rather a subtype of oligodendrogliomas. Further tissue analysis on more specimens is underway. Acid ceramidase shows great potential as a supplemental biomarker in glioma characterization.
Pediatric-Like Intensified Therapy In Adult Acute Lymphoblastic Leukemia: A Single Centre Experience
Authors: Sarah Parisi, Stefania Paolini, Ilaria Iacobucci, Cristina Papayannidis, Mariachiara Abbenante, Antonio Curti, Emanuela Ottaviani, Nicoletta Testoni, Michele Baccarani, Giovanni Martinelli
Journal: Blood (2011)
Second-Line Low-Dose Cytarabine after First-Line Treatment with 5-Azacitidine in Elderly Patients with AML or High-Risk MDS Ineligible for Intensive Chemotherapy. A Retrospective Single Center Analysis
Authors: Christian Jakob, Benjamin Gunther, Katharina Dittberner, Leonard Boger, Philipp Bleienheuft, Frank Breywisch, Frank Rothmann, Stefan Peinert, Georg Maschmeyer
Journal: Blood (2015)
Gremlin-1 Is Overexpressed in Endothelial Cells of Patients with Loeys-Dietz Syndrome Due to Dysregulation of TGF-β Signalling,
Authors: Jasmin Wellbrock, Sara Sheikhzadeh, Veronika Bonk, Leticia Oliveira-Ferrer, Kristin Klaetschke, Thomas Streichert, Carsten Bokemeyer, Yskert von Kodolitsch, Walter Fiedler
Journal: Blood (2011)
Major Bleeding Complications Among Patients Treated with Ibrutinib and Concomitant Antiplatelet, Anticoagulant, or Supplemental Therapy
Authors: Aaron Pavlik, Hallie Barr, Emily Dotson, John C. Byrd, Kristie A. Blum, Farrukh T. Awan, Jennifer A. Woyach, Kami J. Maddocks, Beth A Christian, Jeffrey Jones
Journal: Blood (2016)
Circulating tumor DNA and circulating tumor cells as predictor of outcome in the PRODIGE14-ACCORD21-METHEP2 phase II trial
Authors: F.-C. Bidard, M. Ychou, J. Madic, A. Saliou, O. Bouché, M. Rivoire, F. Ghiringhelli, E. Francois, R. Guimbaud, L. Mineur, F. Khemissa-Akouz, T. Mazard, D. Moussata, W. Cacheux, C. Proudhon, M.-H. Stern, J.-Y. Pierga, T. Stanbury, S. Thezenas, P. Mariani
Journal: Annals of Oncology (2016)
A phase II study of imatinib mesylate (IM) and interferon-alpha (IFNA) in metastatic renal cell carcinoma (RCC)
Authors: B. N. Polite, A. A. Desai, A. C. Peterson, B. Manchen, W. M. Stadler
Journal: Journal of Clinical Oncology (2005)

4689 Background: . RCC is characterized by increased expression of VEGF and PDGF-B, both of which contribute to its angiogenic phenotype. IFNA improves survival in metastatic RCC patients (pts) perhaps in part due to its antiangiogenic properties. IM inhibits PDGFR mediated signal transduction and may thus have antiangiogenic activity as well. Methods: Pts with metastatic RCC were treated with IFNA (9x106 IU s.c. three times per week) and IM (600 mg po daily) starting on day 8. Therapy was continuous and response was evaluated at 8 week intervals using RECIST criteria. Eligibility included measurable disease, ECOG PS 0–2, adequate organ function, and no prior therapy with IFNA and/or IM. Baseline plasma PDGFAA, AB, BB levels were obtained. Results: Between 1/03 and 7/04, 14 patients were treated: median age 63 (range 42–80); male/female, 9/5; race, 12 white, 1 AA, 1 Hispanic; ECOG PS 0/1, 6/8; 13 had a prior nephrectomy; 4 had received prior radiation; 4 patients had received prior therapy, one with IL-2; 12 had clear cell (1 with sarcomatoid features) and 2 had papillary histologies; 13 patients had at least two sites of metastatic disease; 8 patients had anemia at baseline; 3 had hypercalcaemia. Median time from diagnosis of metastatic disease to enrollment was 11 weeks. Best response to therapy: 1 pt. had a PR (7%), 4 had SD (28%), 6 had PD (43%), and 3 were unevaluable due to early withdrawal secondary to toxicities. Median time to progression using the Kaplan-Meier method was 8 wks. After a median follow-up time of 26 wks, median survival has not been reached. 4 patients withdrew from therapy because of toxicities; 5 patients required dose reductions and 8 patients required dose delays. 7 patients (50%) experienced a grade 3 toxicity including fatigue (3), anorexia (2), nausea and vomiting (1), anemia (1), rash (1), edema (1). PDGF AA and AB plasma levels were elevated in 8/9 patients and BB levels were elevated in 9/9 patients, but did not correlate with TTP. Conclusion: Despite the small number of patients, based on a response rate of only 7%, a median time to progression of 2 months, and the significant toxicities, further study of IFNA and IM is not recommended in patients with metastatic RCC. No significant financial relationships to disclose.
Lineage Restricted JAK2V617F Expression and Its Role in Thrombosis and Hemostasis; The Potential Involvement of Endothelial JAK2V617F in Clotting Abnormalities
Authors: Ian S Hitchcock, Michelle E Roh, Veena Sangkhae, Leah Etheridge, Rose Chen, Norma E Fox, Kenneth Kaushansky
Journal: Blood (2011)
P02.01 ABTR-SANO Real-World Pattern of Care Study on Glioblastoma in the Austrian Population
Authors: S. Oberndorfer, C. Marosi, F. Payer, M. Nowosielski, C. Floria, A. Hager, M. Stultschnig, B. Surböck, J. Pichler, A. Wöhrer
Journal: Neuro-Oncology (2016)

Glioblastoma is the most common malignant brain tumor in adults. Since 2005, state-of-the-art treatment consists of maximal safe resection followed by combined radio- and TMZ chemotherapy. A number of population-based outcome and pattern of care studies have documented its successful translation to community practice as well as the associated survival benefit in the general population. However, whether this holds true for Austria has not yet been systematically addressed. To assess real-world patterns of care for glioblastoma in the Austrian population. A close cooperation between the Austrian Brain Tumor Registry and the Society of Austrian Neuro-Oncology is the platform for the conduct of this study. Consensus parameters are abstracted from medical records across all Austrian neurooncology units. All data are entered and stored in a dedicated IT database referred to as ABTR-SANOnet. So far, all patients with newly diagnosed glioblastomas from 01-12/2014 have been recorded (n=310, median age=63 ys) with a last follow-up at 12/2015. Median time from onset of symptoms to diagnostic scan was 7 days (range 0–163 days) and another 8 days to surgical intervention. Total or subtotal resections were achieved in 68.7%. The majority of patients (84.5%) started on a combined treatment schedule with a considerable drop-out rate of 23.4% due to treatment toxicity or early tumor progression. Among elderly patients monotherapies stratified by MGMT promoter methylation status were more prevalent. Herein, we report on the first successful real-world pattern of care study on glioblastoma in Austria. Initial data are in line with internationally reported findings and confirm that the current standard of care has been widely adopted across Austrian neurooncology units. Future multivariate survival analyses will provide important insights in prognostic and therapy-associated factors, which act in Austrian patients.
A randomized double-blind phase II study evaluating the role of maintenance therapy with cabozantinib in high grade undifferentiated uterine sarcoma (HGUS) after stabilization or response to doxorubicin +/- ifosfamide following surgery or in metastatic first line treatment
Authors: I.L. Ray-Coquard, A.P.i. De Tos, C. Coens, M. Huizing, A. Casado Herraez, A.M. Westermann, E. Bompas, H. Earl, M.L. Hensley, A. Negrouk, N. Reed
Journal: Annals of Oncology (2016)
ACTR-21. OCCURRENCE AND IMPLICATIONS OF MYELOSUPPRESSION DURING CONCURRENT THERAPY ON RTOG 0825
Authors: Elizabeth Vera, Michael Scheurer, Renke Zhou, Mark R. Gilbert, Melissa Bondy, Erik Sulman, Ying Yuan, Yanhong Liu, Merideth Wendland, David Brachman, James Bearden, Susan L. McGovern, Steven Wilson, Kevin Judy, H. Ian Robins, Grant Hunter, Ian R. Crocker, Samuel Chao, Vesna Kaluza, Stephanie Pugh, Terri S. Armstrong
Journal: Neuro-Oncology (2016)

Temozolomide-associated myelotoxicity is a rare but significant toxicity that is largely unpredictable and idiosyncratic. Limited data exists on the occurrence during concurrent therapy and impact on future treatment. Glioblastoma patients in NRG Oncology’s RTOG 0825 trial were included in this descriptive report as part of a study of predictors of toxicity. The protocol treatment consisted of 6 weeks of TMZ with radiation therapy (concurrent phase) followed by 12 cycles of TMZ±BEV (adjuvant phase). Included in this report were 367 white glioblastoma patients (61% male, mean age 58 (range 19–82)) from the parent project. Eighty-three patients (23%) experienced myelotoxicity at some point during treatment. During the concurrent phase, treatment was terminated for 77 patients (21%), with the most common reason being adverse event/side effects/complications. Twenty-nine patients (8%) experienced myelotoxicity during the concurrent phase (median 35 days (range 24–63)) leading to treatment termination in 18. Five patients continued to report myelotoxicity within 5 months of treatment termination and one patient died within 1 month of treatment termination. Eleven patients who experienced myelotoxicity during the concurrent phase subsequently were treated with temozolomide during the adjuvant phase. Of these 11, eight (72%) experienced myelotoxicity again during the adjuvant phase or during the follow-up period. Toxicity-related treatment termination during the concurrent phase was more common among patients with myelotoxicity during the concurrent phase (62%) than those without myelotoxicity (17%) (X2=31.8, p<0.01). The occurrence of myelotoxicity during TMZ with concurrent radiation was uncommon, but a serious event. The majority of patients stopped their treatment and several experienced myelotoxicity months afterwards. Patients who continued onto adjuvant therapy later experienced significant myelotoxicity. This descriptive report provides supporting evidence for pre-trial patient screening to identify those who are at risk for significant toxicity. Supported by grants U10CA180868, U10CA180822, U24CA196067, U10CA21661, U24CA114734 NIH Grant 5R01NR013707-04, Genentech.
Phase ii study of mytomicin-c plus uft/lv in patients with metastatic colorectal cancer refractory to standard chemotherapy. subgroup analysis of predictive variables in discriminating early progressors
Authors: C. Sonetto, C. Baratelli, M.P. Brizzi, M. Di Maio, G.V. Scagliotti, M. Tampellini
Journal: Annals of Oncology (2016)
Evidence of Increased Plasma Coagulative Capacity by CloFAL Assay among Pediatric Factor V Leiden and Prothrombin G20210A Heterozygotes with, Versus without, a First-or Second-Degree Family History of Venous Thromboembolism
Authors: Chris Bombardier, Linda J. Jacobson, Marilyn J. Manco-Johnson, Neil A Goldenberg
Journal: Blood (2008)
The Impact of Allogeneic Hematopoietic Stem-Cell Transplantation on Outcome of the Patients with Intermediate-Risk Acute Myeloid Leukemia
Authors: Ying Wang, Hui Wei, Dong Lin, Chunlin Zhou, Bingcheng Liu, Shaowei Qiu, Benfa Gong, Guangji Zhang, Kaiqi Liu, Shuning Wei, Yuntao Liu, Xiaoyuan Gong, Xingli Zhao, Yan Li, Runxia Gu, Yingchang Mi, Jianxiang Wang
Journal: Blood (2016)
Superior Complete Response Rate (CR) and Progression-Free Survival (PFS) with Bortezomib-Thalidomide-Dexamethasone (VTD) Versus Thalidomide-Dexamethasone (TD) As Consolidation Therapy After Autologous Stem-Cell Transplantation (ASCT) in Multiple Myeloma (MM)
Authors: Michele Cavo, Lucia Pantani, Francesca Patriarca, Maria Teresa Petrucci, Monica Galli, Francesco Di Raimondo, Giuseppe Rossi, Antonio Palumbo, Paola Tacchetti, Massimo Offidani, Vittorio Montefusco, Franco Narni, Tonino Spadano, Claudia Cellini, Norbert Pescosta, Luca Baldini, Antonio Ledda, Tommaso Caravita Di Toritto, Annalisa Pezzi, Antonietta Falcone, Chiara Nozzoli, Renato Zambello, Luciano Masini, Filippo Gherlinzoni, Maria Concetta Petti, Daniele Derudas, Stelvio Ballanti, Valerio De Stefano, Michele Baccarani
Journal: Blood (2011)
RTHP-19. ANALYSIS OF GLIOBLASTOMA PHYSICAL CHARACTERISTICS IN PATIENTS BENEFITING FROM TUMOR TREATING ELECTRIC FIELDS THERAPY
Authors: Pyay San
Journal: Neuro-Oncology (2016)

Tumor treating electric fields (TTFields) are an established treatment for glioblastoma (GBM) patients. However, the anatomical and physical characteristics of the brain and tumor contributing to treatment efficacy are not well understood. We contoured gross tumor volume (GTV) using ScanIP and measured tumor size according to the RANO criteria on 5 patients with recurrent GBMs who exhibited a benefit from TTFields (cohort 1) and 5 who did not show any change (cohort 2). Tumor surface area and geometric centroid distance (GCD) from the bilateral ventricles were computed. Wilcoxon rank sum test was used to compare these physical parameters between the two cohorts. The results showed that the respective median GTV was 11.6 cm3 and 38.1 cm3 (P=0.0591), while the respective median GCD was 5.0 cm and 5.3 cm (P=0.6761), in cohort 1 and 2. The tumor size had a median of 8.2 cm2 in cohort 1, as compared to a median of 53.9 cm2 in cohort 2 (P=0.0591). The surface area had a median of 56.2 cm2 in cohort 1, as compared to a median of 214.0 cm2 in cohort 2 (P=0.4034). After removing an outlier from cohort 1 and another from cohort 2, the respective median GTV was 9.7 cm3 and 41.3 cm3 (P=0.1003), and the respective median surface area was 46.5 cm2 and 236.0 cm2 (P=0.0304). The respective median surface area/GCD was 13.3 cm and 38.9 cm (P=0.0304) and the respective median GTV/GCD was 2.7 cm2 and 8.5 cm2 (P=0.0304). The data suggest that the ratio of surface area/GCD and GTV/GCD, which are proportional to the tissue capacitance, may be an important parameter for optimizing TTFields efficacy in the treatment of GBM. These interesting findings on a small cohort of patients will need to be validated in a larger dataset.
IL-25 stimulates M2 macrophage polarization and thereby promotes mitochondrial respiratory capacity and lipolysis in adipose tissues against obesity
Authors: Juan Feng, Lingyi Li, Zhiying Ou, Qiao Li, Baoyong Gong, Zhenxian Zhao, Weiwei Qi, Ti Zhou, Jun Zhong, Weibin Cai, Xia Yang, Aiping Zhao, Guoquan Gao, Zhonghan Yang
Journal: Cellular and Molecular Immunology (2017)

Obesity and associated metabolic diseases are characterized by a chronic low-grade inflammatory state with the infiltration of many inflammatory cells, especially macrophages. Immune molecules, including some cytokines, have a close relationship with metabolism. Interleukin (IL)-25 is a member of the IL-17 cytokine family that can regulate macrophages and alleviate some metabolic dysfunction; however, its role and mechanisms in lipid metabolism remain to be extensively clarified. Human serum and liver biopsy specimens, high-fat diet-induced obesity mice and DB/DB (Lepr-/-) animal models were used to examine IL-25 expression in obesity and nonalcoholic fatty liver diseases (NAFLD). To observe the role of IL-25 in lipid metabolism, model mice were administered with IL-25 or adoptively transferred with IL-25-educated macrophages in vivo, whereas bone marrow-derived macrophages, the macrophage cell line RAW264.7 and adipocytes differentiated from 3T3-L1 were used in vitro. IL-25 was decreased in NAFLD patients and obese mice. In addition, IL-25 reduced body weight gain and lipid accumulation, enhanced lipid uptake by macrophages and increased the expression of lipolysis and β-oxidation enzymes via alternatively activating macrophages. IL-25 also promoted lipolysis and suppressed lipogenesis in adipocytes co-cultured with the IL-25-educated macrophages. Furthermore, IL-25 improved the mitochondrial respiratory capacity and oxygen consumption rate of macrophages and produced more NAD+/NADH and ATP. In conclusion, IL-25 can stimulate M2 macrophage polarization and thereby promote lipolysis and mitochondrial respiratory capacity, highlighting the potential for IL-25 to be used as a therapeutic agent against obesity and associated metabolic syndromes.
P07.02 Diagnostic pitfalls in brainstem lesions mimicking gliomas in adults
Authors: A. Duran-Peña, C. Ramirez, F. Ducray, L. Bauchet, J. M. Constans, S. Grand, J. S. Guillamo, D. Frappaz, C. Houillier, H. Loiseau, F. Laigle-Donadey
Journal: Neuro-Oncology (2016)