tbuckley/cabot-search huggingface dataset:
P04.01 Characterization of microglia/macrophage phenotypes in glioma patient-derived xenograft mouse models
Authors: A. Michelucci, A. Golebiewska, A. Oudin, A. Schuster, R. Balling, S. P. Niclou
Journal: Neuro-Oncology (2016)

A major contributing factor to glioma development and progression is its ability to evade the immune system. Malignant gliomas release factors that recruit resident microglia, macrophages and other peripheral immune cells to the tumor site and transform them into tumor-supportive cells. Here, we investigate the contribution of microglia/macrophages (MMs) in intrinsic tumor escape mechanisms by analysing their phenotypic and functional adaptation in the tumorigenic process. Specifically, we aim to elucidate at which stage MMs adopt an immune-suppressed phenotype and to study how microglial cells affect the functional properties of glioma (i.e. invasion, angiogenesis). We take advantage of established orthotopic patient-derived xenograft models generated in nude mice, which, although deficient in T lymphocytes, do mount an efficient innate immune response and accumulate large numbers of MMs in xenografted gliomas, similar to what is seen in patients. We combine immunohistochemistry with flow cytometry analysis and we sort specific immune cell populations to analyse their gene expression signatures. We analysed three different tumor phenotypes, which in our hands represent different stages along tumor progression as well as recapitulate strong inter- and intra-tumor heterogeneity present in patients. A highly ‘invasive’ phenotype with an apparent normal brain vasculature, a highly ‘angiogenic’ phenotype displaying necrotic areas and microvascular proliferation and an ‘intermediate’ phenotype combining features of invasion and vessel abnormalities. Iba1-positive cells accumulate specifically depending on the tumor phenotype within and/or around the tumor region showing different morphologies. CD11b-positive cells from the three tumor types express characteristic markers and have specific gene signatures. In addition, Iba1-positive cells show intra-tumor regional heterogeneity, displaying different morphologies in the tumor core, the infliltration zone and the distal area. The analysis of our mouse models shed light on the spatial and temporal heterogeneity of MMs polarization in gliomas. Functional and transcriptional analysis of MMs isolated from these three tumor phenotypes pave the way for the generation of systematic/-omics data to infer gene regulatory networks allowing a detailed characterization of MMs polarization associated to the different tumors.
Phase I/II study of induction chemotherapy using carboplatin plus irinotecan and sequential thoracic radiotherapy (TRT) for elderly patients with limited-stage small-cell lung cancer (LD-SCLC): The final results of TORG 0604
Authors: Y. Misumi, H. Okamoto, K. Naoki, Y. Hosomi, T. Ogura, N. Masuda, K. Minato, T. Yokoyama, K. Kishi, M. Nishikawa, T. Kato, N. Seki, I. Goto, K. Watanabe
Journal: Annals of Oncology (2016)
MicroRNA-7a2 suppression causes hypogonadotropism and uncovers signaling pathways in gonadotropes
Authors: William F. Crowley, Ravi Balasubramanian
Journal: Journal of Clinical Investigation (2017)

MicroRNAs (miRNAs) have emerged as important regulators of a variety of biological processes and pathways. In this issue of the JCI, Ahmed et al. reveal that miR-7a2 is a critical regulator of sexual maturation and reproductive function, as mice lacking miR-7a2 develop hypogonadotropic hypogonadism and infertility. Using a bioinformatics approach, the authors identified several miR-7a2 target genes and pathways that have not been previously associated with gonadotropin biosynthesis and/or secretion. Together, these results identify miR-7a2-regulated genes involved in reproductive hormone biosynthesis pathways and provide a framework for future studies aimed at understanding rare reproductive conditions.
Ceritinib in ROS1-rearranged non-small-cell lung cancer: a Korean nationwide phase II study
Authors: S.M. Lim, B.C. Cho, H.R. Kim, J.-S. Lee, K.H. Lee, Y.-G. Lee, Y.J. Min, E.K. Cho, S.-S. Lee, B.-S. Kim, M.Y. Choi, H.S. Shim, J.H. Chung, Y.L. Choi, M.J. Lee, M.-J. Ahn
Journal: Annals of Oncology (2016)
Direct Comparison of In Vivo Fate of Second and Third-Generation CD19-Specific Chimeric Antigen Receptor (CAR)-T Cells in Patients with B-Cell Lymphoma: Reversal of Toxicity from Tonic Signaling
Authors: Diogo Gomes da Silva, Malini Mukherjee, Madhuwanti Srinivasan, Olga Dakhova, Hao Liu, Bambi Grilley, Adrian P. Gee, Sattva S. Neelapu, Cliona M. Rooney, Helen E Heslop, Barbara Savoldo, Gianpietro Dotti, Malcolm K. Brenner, Maksim Mamonkin, Carlos A. Ramos
Journal: Blood (2016)
GENT-02. GENETIC ALTERATIONS ASSOCIATED WITH RADIOGRAPHIC FEATURES OF PROGRESSION OF IDH-MUTANT/1p19q CO-DELETED GLIOMAS
Authors: Sameer H. Halani, Chad A. Holder, Brent Griffith, Michael Nalisnik, Jennifer Eschbacher, Laila Poisson, Jose Enrique Velazquez Vega, Jeffrey J. Olson, Lee Cooper, Daniel Brat
Journal: Neuro-Oncology (2016)

Lower-grade gliomas with IDH-mutations and 1p/19q co-deletion, or oligodendroglioma, represent an important subset with unpredictable clinical courses. Disease progression can be monitored with magnetic resonance imaging (MRI), most notably by the presence of contrast-enhancement and radiographic necrosis. We investigated molecular markers associated with radiographic features of disease progression in oligodendroglioma to help explain variations in clinical course. Fifty-five patients with oligodendroglioma were selected from The Cancer Genome Atlas with pre-operative MRIs available from The Cancer Imaging Archive. MRIs were reviewed for unequivocal contrast enhancement (CE+) and radiographic necrosis (rNec). Statistical analysis was performed to identify relationships between CE and rNec and WHO histological grade, cellular proliferation (based on Ki-67 expression), key genetic alterations, and copy number events (CNE). Patients with CE+ (n=35) outnumbered those non-CE (n=20) patients; 10 CE+ tumors demonstrated rNec. Distribution of WHO grade was nearly even (grade II n= 29; grade III n=25). CE+ and rNec were associated with higher WHO histological grade (p<0.001), increased Ki-67 expression (p=0.003), and worse overall survival (log-rank p=0.04). Tumors with NOTCH1 mutations were almost exclusively CE+ (13 of 14). 77.8% (14 of 18) of tumors with PI3K mutations and 82.4% (14 of 17) with FUBP1 mutations were CE+. CIC mutations were evenly distributed in both CE+ (n=16) and non-CE (n=9) groups. Key CNEs included gain of chromosomes 7p (n=7), 11p (n=9), and loss of chromosome 15q (n=9). Tumors with these CNEs were exclusively CE+. The use of radiographic contrast-enhancement as a surrogate for disease progression in this investigation revealed key genetic alterations and copy number variations that may help predict aggressive behavior in oligodendroglioma. These genetic signatures can better inform prognostication and may contain potential progression-related targets for future drug therapies.
Neridronate (NE) for the Treatment of Osteoporosis In Patients with β-Thalassemia: Results from an Italian Multicenter Randomized, Open Label, Phase II Trial
Authors: Gian Luca Forni, Silverio Perrotta, Caterina Borgna Pignatti, Domenico Giuseppe D'Ascola, Bruno Nobili, Lorella Pitrolo, Giovanni Quarta, Paolo Rigano, Laura Zanaboni, Ernesto Palummeri
Journal: Blood (2010)
Efficacy of Ofatumumab and High-Dose Methylprednisolone for the Treatment of Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)
Authors: Melissa L. Teichman, Viet Q. Ho, Lodovico Balducci, Celeste M. Bello, Javier Pinilla-Ibarz
Journal: Blood (2011)
EXTH-41. THE ANTI-PROLIFERATIVE EFFECTS OF RF EMF AMPLITUDE-MODULATED (AM RF EMF) AT TUMOR SPECIFIC FREQUENCIES ON GLIOBLASTOMA CELLS
Authors: Hugo Jimenez, Minghui Wang, Sambad Sharma, Denise Herpai, Glenn J Lesser, Waldemar Debinski, Frederico Costa, Alexandre Barbault, Carl Blackman, Boris Pasche
Journal: Neuro-Oncology (2016)

Whole body administration of low-level radiofrequency electromagnetic fields, amplitude-modulated (AM RF EMF) at specific frequencies ranging from 400 Hz to 21 kHz showed efficacy in advanced breast cancer and hepatocellular carcinoma (HCC) (Barbault, Costa et al., 2009, Costa de Oliveira et al., 2011). In vitro studies demonstrated that AM RF EMF treatment inhibits cancer cell growth in a tumor-specific manner (Zimmerman, Pennison et al., 2012). Indeed, the growth of both HCC (HepG2 and Huh7) and breast cancer (MCF-7) cells was inhibited when exposed to corresponding tumor-specific frequencies for 3 hours per day for 7 days. The GBM cell line U-251 as well as two glioblastoma (GBM) low passage explant cells (BTCOE-4536 and BTCOE-4795) were exposed to 27.12 MHz RF EMF modulated at GBM-specific frequencies using exposure systems designed to replicate human exposure levels. Control cells were not exposed to RF EMF. GBM cells were cultured for seven days receiving GBM-specific treatment for three hours daily. The specific absorption rate (SAR) of AM RF EMF was 0.4 W/kg, which is identical to the highest SAR measured in patients receiving treatment with this therapy. Proliferation was quantified via the tritiated thymidine incorporation assay. Neurosphere-formation was counted at 7 days post treatment. Statistics were performed by student’s T-test. The growth of U-251, BTCOE 4536 and BTCOE 4795 cell lines was decreased by 19% (N=10; p=0.0018), 23% (N=4; p=0.0348) and 14.5% (N=10; p=0.0431) following exposure to tumor-specific AM RF EMF. Neurosphere-forming ability of the U-251 and BTCOE-4795 cell lines was inhibited by 48.0% (N=6; p=0.0040) and 31.7% (N=6; p=0.0002) following exposure to tumor-specific AM RF EMF. GBM-specific AM RF EMF inhibits proliferation of three different GBM cell lines and neurosphere-forming ability which suggests that AM RF EMF should be further studied as a potentially new treatment modality of GBM.
Phase 2 of intra-arterial hepatic (IAH) bevacizumab with systemic chemotherapy (CT) in second line treatment of liver metastases of colorectal cancer (LMCRC)
Authors: M.P. Ducreux, O. Glehen, G. Tergemina-Clain, D. Smith, B. Lacas, V. Boige, D. Malka, J.-P. Pignon, E. Dupont-Bierre, R. Guimbaud
Journal: Annals of Oncology (2016)
[18F](2<i>S</i>,4<i>R</i>)4-Fluoroglutamine PET Detects Glutamine Pool Size Changes in Triple-Negative Breast Cancer in Response to Glutaminase Inhibition
Authors: Rong Zhou, Austin R. Pantel, Shihong Li, Brian P. Lieberman, Karl Ploessl, Hoon Choi, Eric Blankemeyer, Hsiaoju Lee, Hank F. Kung, Robert H. Mach, David A. Mankoff
Journal: Cancer Research (2017)

Abstract Glutaminolysis is a metabolic pathway adapted by many aggressive cancers, including triple-negative breast cancers (TNBC), to utilize glutamine for survival and growth. In this study, we examined the utility of [18F](2S,4R)4-fluoroglutamine ([18F]4F-Gln) PET to measure tumor cellular glutamine pool size, whose change might reveal the pharmacodynamic (PD) effect of drugs targeting this cancer-specific metabolic pathway. High glutaminase (GLS) activity in TNBC tumors resulted in low cellular glutamine pool size assayed via high-resolution 1H magnetic resonance spectroscopy (MRS). GLS inhibition significantly increased glutamine pool size in TNBC tumors. MCF-7 tumors, with inherently low GLS activity compared with TNBC, displayed a larger baseline glutamine pool size that did not change as much in response to GLS inhibition. The tumor-to-blood-activity ratios (T/B) obtained from [18F]4F-Gln PET images matched the distinct glutamine pool sizes of both tumor models at baseline. After a short course of GLS inhibitor treatment, the T/B values increased significantly in TNBC, but did not change in MCF-7 tumors. Across both tumor types and after GLS inhibitor or vehicle treatment, we observed a strong positive correlation between T/B values and tumor glutamine pool size measured using MRS (r2 = 0.71). In conclusion, [18F]4F-Gln PET tracked cellular glutamine pool size in breast cancers with differential GLS activity and detected increases in cellular glutamine pool size induced by GLS inhibitors. This study accomplished the first necessary step toward validating [18F]4F-Gln PET as a PD marker for GLS-targeting drugs. Cancer Res; 77(6); 1476–84. ©2017 AACR.
Building discontinuous liver sinusoidal vessels
Authors: Courtney T. Griffin, Siqi Gao
Journal: Journal of Clinical Investigation (2017)

Blood vessels have a unified mission to circulate blood throughout the body; however, they have additional diverse and specialized roles in various organs. For example, in the liver, discontinuous sinusoids, which are fenestrated capillaries with intercellular gaps and a fragmented basement membrane, facilitate delivery of macromolecules to highly metabolic hepatocytes. During embryonic development, discontinuous sinusoids also allow circulating hematopoietic progenitor and stem cells to populate the liver and promote blood cell differentiation. In this issue of the JCI, Géraud et al. describe an essential role for the transcription factor GATA4 in promoting the development of discontinuous sinusoids. In the absence of liver sinusoidal GATA4, mouse embryos developed hepatic capillaries with upregulated endothelial cell junction proteins and a continuous basement membrane. These features prevented hematopoietic progenitor cells from transmigrating into the developing liver, and Gata4-mutant embryos died from subsequent liver hypoplasia and anemia. This study highlights the surprising and extensive transcriptional control GATA4 exercises over specialized liver vascular development and function.
An open-label, multinational, multicentre, phase IIIB umbrella study of subcutaneous trastuzumab with or without chemotherapy or pertuzumab in patients with HER2-positive early or metastatic breast cancer (UmbHER1): Interim safety results from early breast cancer studies
Authors: X. Pivot, C. Poole, M. Martín, J. Gligorov, C.H. Barrios, E. Vrdoljak, L. Gianni, A.J. Ten Tije, Z. Machackova, M. Truman, G. Steger
Journal: Annals of Oncology (2016)
Impact of pharmacist outpatient interventions on management of Lenvatinib for thyroid cancer patients
Authors: Shinya Uozumi, Shinya Suzuki, Tomoko Yamazaki, Tomoka Okano, Tomohiro Enokida, Tetsuro Wakasugi, Susumu Okano, Shinichiro Saito, Makoto Tahara
Journal: Annals of Oncology (2016)
Patterns and correlates of adjuvant breast cancer endocrine therapy use.
Authors: T. M. Pini, J. J. Griggs, A. S. Hamilton, S. J. Katz
Journal: Journal of Clinical Oncology (2011)

510 Background: We examined patterns of endocrine therapy and correlates of non-persistence in a population-based sample of women with breast cancer. Methods: We surveyed 2245 women newly diagnosed with breast cancer between 6/05 and 2/07 and reported to the Detroit and Los Angeles SEER registries. Patients were re-surveyed approximately 4 years after diagnosis (expected n=1520). Logistic regression was used to examine factors associated with self-reported current use of therapy of 2 or more years. Results: Among 707 patients in the preliminary sample, 455 had an estrogen receptor-positive cancer and were disease-free. Of these, 86 (19%) reported never starting endocrine therapy, 49 (11%) started but stopped, and 320 (70%) reported current use. Common reasons for never starting therapy were doctor-related: the doctor said treatment was not needed (40%), the doctor left the decision about treatment to the patient (13%), or the treatment was never discussed with a doctor (7%). Patient-related reasons were less common: a physician recommended treatment but the patient declined (11%), patient concerns about side effects (9%) or the expense of the medication (4%). Among women who started but stopped therapy: 22% were on therapy for <1 yr, 39% 1-2 yrs, and 33% >2 yrs. The most common reasons for stopping therapy were patient-related: side effects (45%) or concerns about adverse effects (33%). A quarter of patients who stopped did so because of a doctor recommendation. In multivariate analysis among patients who started therapy, having a medical oncologist most involved in follow-up care compared to other physicians was associated with greater current use (OR 2.69, 95% CI 1.35-5.37, p=0.005) while less prescription coverage by insurance was associated with lower use (OR 0.48, 95% CI 0.25-0.93, p=0.03), controlling for age, education, and income. Conclusions: Many patients who do not start therapy report that their doctor did not recommend it which suggests marginal indications for treatment. Side-effects and cost of treatment warrant continued attention as they are common reasons patients start but stop therapy. The role of a medical oncologist during survivorship may be particularly important in achieving a full course of endocrine therapy.
P07.13 Aberrant paramagnetic/diamagnetic MRI signals outside the tumor volume are frequent findings that evolve overtime in adult patients surviving two or more years after brain irradiation
Authors: S. Yust-Katz, E. Inbar, J. Lukman, N. Micheli, D. Limon, T. Siegal
Journal: Neuro-Oncology (2016)

require any further treatments and was on observation with imaging only for 14 months until another area of progression was seen.CONCLUSION: After treatment of a neoplasm, if unexpected clinical or imaging evidence of recurrence is present, it may be a foreign body reaction to hemostatic material used during the initial surgery.The implications of this case lie in recognizing this entity to avoid unnecessary procedures.Given the technical variability of advanced MRI techniques, there are limits to the sensitivity and specificity of such.The standardization of advanced MRI is well recognized as a pressing clinical and research need. P07.
Acute myeloid leukemias with reccurent genetic abnormalities:frequent assessment of minimal residual disease and treatmentof molecular relaps with chemotherapy. Acute myeloid leukemiaswith reccurent genetic abnormalities: frequent assessment ofminima
Authors: Michael Doubek, Yvona Brychtová, Jana Borkovcová, Marta Krejčí, Ivo Palásek, Dana Dvořáková, Jiří Mayer
Journal: Leukemia (2005)
Correction of the Skin Defect in Murine Recessive Dystrophic Epidermolysis Bullosa by Bone Marrow Derived SLAM Family Receptor Enriched Cells.
Authors: Jakub Tolar, Ron T. McElmurry, Hisham Bazzi, Lily Xia, Akemi Ishida-Yamamoto, Angela M. Christiano, Bruce R. Blazar
Journal: Blood (2007)
Unveiling the “Magic” of Diabetes Remission After Weight-Loss Surgery
Authors: Jennifer Abbasi
Journal: JAMA (2017)

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Y-90 radioembolization in the treatment of colorectal cancer that is metastatic to the liver.
Authors: A. R. Cucci, E. W. Martin, M. Bloomston, C. R. Schmidt, N. A. Mayr, L. Wei, T. Bekaii-Saab
Journal: Journal of Clinical Oncology (2011)

593 Background: Y-90 radioembolization has shown promise in the treatment of unresectable metastatic colorectal cancer (mCRC) and primary hepatocellular carcinoma (HCC). The goal of our study was to assess the efficacy in patients with refractory mCRC who underwent Y-90 radioembolization. Methods: Patients with unresectable mCRC to the liver underwent treatment at the Ohio State University with resin microspheres. Response to treatment or progression of disease was assessed by CT imaging per RECIST criteria. Overall survival (OS) and progression free survival (PFS) were estimated by Kaplan-Meier method. Log-rank test was used to compare the survival curves between the groups. The Cox-regression model was used to explore any association between time to treatment and PFS (or OS). Results: 24 patients with a mean age of 63 years old were included. 54% of patients had extrahepatic disease, 67% had hepatic bilobar involvement, and more than 80% of our patients had more than two chemotherapy regimens prior to initiation of Y-90 radioembolization. There were no objective responses radiographically. 5 patients had a CEA response. The estimated median PFS and OS were 3.9 months (CI 95%: 2.4,4.8) and 8.9 months (CI 95%: 4.2,16.7), respectively. Patients with any CEA response to treatment tended to have a significantly longer PFS (4.8 months vs. 2.7 months, p=0.088), but no significant association with OS (p=0.64). The presence of extrahepatic disease prior to initiation of treatment resulted in a significantly lower PFS (2.9 vs. 5.1 months, p=0.076) but no significant difference in OS (p=0.86). Patients older than 65 appeared to have an improvement in PFS compared to younger patients (4.6 vs. 2.4 months, p=0.052). There was no significant association between the time to initiation of treatment and PFS (p=0.63) or OS (p=1). Conclusions: Y-90 radioembolization appears to have promising activity in patients with refractory unresectable liver metastasis from mCRC. Factors such as older age and absence of extrahepatic disease may be associated with improved outcomes. CEA response may be a surrogate marker for benefit. Large randomized studies need to confirm our findings. No significant financial relationships to disclose.
Use of an Electronic Medical Record (EMR) Database to Identify a Real-World Cohort of US Patients (Pts) with Myelodysplastic Syndromes (MDS)
Authors: Xiaomei Ma, Arlene S. Swern, Pavel Kiselev, Albert Fliss, Jane J. Lu, Bart L. Scott, David P. Steensma, Mary M. Sugrue
Journal: Blood (2015)