tbuckley/cabot-search huggingface dataset:
MNGO-19. USING BEVACIZUMAB TO MANAGE RECURRENT/ PROGRESSIVE MENINGIOMAS: A RETROSPECTIVE ANALYSIS
Authors: Ashley Sumrall, Daniel Haggstrom, Serena Perera, David Jennings, Stuart Burri, Anthony Asher
Journal: Neuro-Oncology (2016)

Meningiomas are common, often indolent, primary brain tumors. Unfortunately, once maximum safe resection and radiation options are exhausted, patients with progression or recurrence are left with few remaining effective therapies. Angiogenesis via VEGF-mediated pathways is felt to be an etiology for progression of these tumors, making it a reasonable target for therapy. We performed a retrospective review of adult patients managed with bevacizumab (BEV) for recurrent or progressive meningiomas between 2011-2016. Seven patients, three with progressive grade I meningiomas and four with recurrent grade II atypical meningiomas, were treated with BEV. Median KPS for included patients was 90. Dosing schedules varied, but usually consisted of 10 mg/kg IV every 2 weeks. Mean exposure to BEV was approximately 16 months (6 months to 44 months). Of note, two patients were treated for over 2 years with BEV, and each developed proteinuria which caused treatment cessation. Off BEV, both patients have remained radiographically stable. In contrast, four patients were treated with 6 cycles of BEV at 10 mg/kg IV every 2 weeks, followed by observation. Three of those patients had initial partial responses, and all six of them currently have stable disease. PFS for progressive grade I meningiomas was 33.5 months, and all patients are still living. PFS for recurrent grade II meningiomas was 21.1 months, and one patient died from complications felt to be unrelated to BEV. Therapy was well-tolerated in the group which received six cycles. One patient had a CVA which was felt to be radiation-induced. Other retrospective series examining BEV in patients with recurrent/ progressive meningiomas tend to favor prolonged exposure to BEV and have confirmed bleeding complications such as intracerebral hemorrhage or gastrointestinal perforation. We favor a more conservative approach, planning for an initial 6 month course, followed by observation if patients are clinically and radiographically stable.
Denosumab for the prevention of symptomatic skeletal events (SSEs) in patients with bone-metastatic breast cancer: A comparison with skeletal-related events (SREs)
Authors: J.-J. Body, R. von Moos, A. Lipton, M. Martin, I. Diel, G. Steger, K. Tonkin, R. de Boer, H.-S. Radcliffe, D. Niepel, A.T. Stopeck
Journal: Annals of Oncology (2016)
Co-Culture of Myeloma and Endothelial Cells: Defibrotide Downregulates Heparanase and Pro-Angiogenic Growth Factors.
Authors: Cinara Echart, Maria Distaso, Laura Ferro, Mario Boccadoro, Antonio Palumbo, Constantine Mitsiades, Kenneth Anderson, Paul Richardson, Massimo Iacobelli
Journal: Blood (2007)
Association and expression of the antigen-processing gene <i>PSMB8</i> , coding for low-molecular-mass protease 7, with vitiligo in North India: case-control study
Authors: P. Dani, N. Patnaik, A. Singh, A. Jaiswal, B. Agrawal, A.A. Kumar, S.R. Varkhande, A. Sharma, U. Vaish, P. Ghosh, V.K. Sharma, P. Sharma, G. Verma, H.K. Kar, S. Gupta, V.T. Natarajan, R.S. Gokhale, R. Rani
Journal: British Journal of Dermatology (2017)

Vitiligo is a multifactorial, autoimmune, depigmenting disorder of the skin where aberrant presentation of autoantigens may have a role. To study the association of two antigen‐processing genes, PSMB8 and PSMB9, with vitiligo. In total 1320 cases of vitiligo (1050 generalized and 270 localized) and 752 healthy controls were studied for the PSMB9 exon 3 G/A single‐nucleotide polymorphism (SNP), PSMB8 exon 2 C/A SNP and PSMB8 intron 6 G/T SNP at site 37 360 using polymerase chain reaction (PCR)–restriction fragment length polymorphism. Real‐time PCR was used for transcriptional expression of PSMB8 and cytokines. Expression of ubiquitinated proteins and phosphorylated‐p38 (P‐p38) was studied by Western blotting. Significant increases in PSMB8 exon 2 allele A (P <2.07 × 10−6, odds ratio 1·93) and genotypes AA (P <1.03 × 10−6, odds ratio 2·51) and AC (P <1.29 × 10−6, odds ratio 1·63) were observed in patients with vitiligo. Interferon‐γ stimulation induced lower expression of PSMB8 in peripheral blood mononuclear cells of cases compared with controls, suggesting impaired antigen processing, which was confirmed by accumulation of ubiquitinated proteins in both lesional and nonlesional skin of patients with vitiligo. Expression of proinflammatory cytokines – interleukin (IL)‐6, IL‐1β and IL‐8 – was higher in the lesional skin. P‐p38 expression was variable but correlated with the amount of ubiquitinated proteins in the lesional and nonlesional skin, suggesting that the inflammatory cytokine responses in lesional skin could be a result of both P‐p38‐dependent and ‐independent pathways. The PSMB8 exon 2 SNP is significantly associated with vitiligo. Accumulation of ubiquitinated proteins in skin of cases of vitiligo suggests their aberrant processing, which may promote the development of the disease.
NIMG-46. CHARACTERIZATION OF GLIOBLASTOMA SUBTYPES BY INTEGRATIVE ANALYSIS OF MATCHED GENE EXPRESSION AND ADVANCED MAGNETIC RESONANCE IMAGING DATA
Authors: Carl Philipp Simon-Gabriel, Astrid Weyerbrock, Konstanze Guggenberger, Dietmar Pfeifer, Elias Kellner, Oliver Schnell, Horst Urbach, Irina Mader, Dieter Henrik Heiland
Journal: Neuro-Oncology (2016)

The aim of this study was the radiogenomic characterization of glioblastoma subtypes (Verhaak et al. 2010) by integrative analysis of matched magnetic resonance (MR) imaging and gene expression data (GED) in glioblastoma. GED from biopsies obtained by MR-based neuronavigation from 21 glioblastoma patients having had preoperative perfusion, diffusion and MR spectroscopic (MRS) imaging were analyzed using in-house tools, including weighted gene co-expression network analysis (WGCNA) and gene set enrichment analysis (GSEA). Integrative analysis revealed that the proneural glioblastoma subtype tends to have high creatine in MRS, low cerebral blood volume (CVB) and small vessel size (VS) in perfusion imaging, as well as low fractional anisotropy (FA) and high mean diffusivity (MD) in diffusion imaging. The classical subtype showed low values for glutamate and glutamine in MRS, large VS in perfusion as well as high FA and low MD in diffusion imaging. Finally, the mesenchymal subtype had low creatine in MRS, high CBV in perfusion as well as high FA and low MD in diffusion imaging. In addition to the glioblastoma subtype characterization, biologic pathways correlating with different imaging parameters were identified: N-acetylaspartate was linked to oligodendrocytic differentiation and neural development, CBV correlated with genes of the endothelial growth factor and the endothelial-mesenchymal transition (EMT) pathways, VS with hypoxia pathways, FA with genes from the NFkB and the endothelial-mesenchymal transition pathways, and MD was linked to the expression of genes relating to neural development and neural functions. Finally, survival analysis revealed correlations of imaging features with patient prognosis. High N-acetylaspartate, low FA or high MD were linked to a longer progression-free survival in our study population. Although these results remain to be validated in a larger study population our research showed that advanced MR imaging techniques can help discriminate between glioblastoma subtypes and improve prognosis evaluation in glioblastoma.
Risk of Relapse (REL) after Umbilical Cord Blood Transplantation (UCBT) in Patients with Acute Leukemia: Marked Reduction in Recipients of Two Units.
Authors: Michael R. Verneris, Claudio Brunstein, Todd E. DeFor, Juliet Barker, Daniel J. Weisdorf, Bruce R. Blazar, Jeffrey S. Miller, John E. Wagner
Journal: Blood (2005)
IMST-47. IDENTIFICATION AND EXPANSION OF GLIOMA-SPECIFIC T CELLS USING TCR Vβ EXPRESSION
Authors: Catherine Flores, Tyler Wildes, Jeffrey Drake, Kyle Dyson, Duane Mitchell
Journal: Neuro-Oncology (2016)

Study of T-cell traits that predict response to therapy is complicated by the challenge that brain tumor antigens are largely uncharacterized. In other solid tumors, adoptive cell therapy has been demonstrated to be a highly efficacious immunotherapeutic strategy. Our OBJECTIVE is to demonstrate that we have generated an adoptive cell therapy platform that leads to the expansion and persistence of tumor-specific T lymphocytes without the need for prior antigen identification. Instead, TCR Vβ expression can be used to both identify and enrich for the tumor-specific T cell population. We employ bone marrow-derived dendritic cells pulsed with tumor-derived RNA to ex vivo expand tumor-specific T lymphocytes (TTRNA-T cells). After adoptive transfer of TTRNA-T cells, we are able to isolate the tumor-reactive T cells using flowcytometry based TCR Vβ spectratyping. These T cells can then be reliably expand from splenocytes of previously immunized mice. Functionality assays demonstrate that TTRNA-T cells with TCR Vβ families predicted to have high affinity to tumors were responsible for anti-tumor immunity. Adoptive cellular therapy using T cells expressing TCR Vβ 6 and TCR Vβ 8.1, 8.2 against intracranial tumor led to cures in 60% of treated mice. We further identify that the in vivo expansion of TCR Vβ 6+ T cells is associated with long term survival. Failure of the persistence of these T cells is directly associated with tumor escape. In patients that received adoptive cell therapy using our platform, we observed selective relative expansion of specific TCR Vβ families post-vaccination. Our methods allow us to generate highly tumor-reactive T cell populations without the need for identifying tumor antigens. We are currently employing these analyses in clinical trials of adoptive cellular therapy targeting pediatric and adult gliomas under development at our center (FDA IND BB-14058).
Effect of Kampo medicine Juzen-taiho-to on adverse events induced by cetuximab.
Authors: S. Morimoto, M. Shimada, N. Kurita, T. Iwata, M. Nishioka, K. Yoshikawa, T. Miyatani, C. Mikami, H. Kashihara
Journal: Journal of Clinical Oncology (2011)

396 Background: Cetuximab is now considered a standard treatment for advanced or unresectable colorectal cancer, unfortunately patients suffer a skin reaction as the main indication of the toxicity of cetuximab. It is recently reported that Kampo medicine (Goshajinkigan) is considered to be an effective agent for the neuropathy of oxaliplatin. Kampo medicine “Juzen-taiho-to” (TJ-48, Tsumura CO. Ltd.), which consists of 10 component herbs, is known as a tonic agent which improves the general systemic condition of cancer patients by reducing the adverse effects of chemotherapy, radiation therapy, and surgical treatment and to inhibit metastases. The aim of this study was to clarify the efficacy of TJ-48 for adverse events associated with cetuximab therapy. Methods: From 2009, cetuximab was administered initially at a dose of 400 mg/m 2 followed by weekly infusions at 250 mg/m 2 to 20 patients with non-resectable or recurrent colorectal cancer. Eighteen patients received oral administration of 7.5 g/day of TJ-48 (TJ-48 group) every day in the first course and 7 patients did not receive TJ-48 (Control group). Adverse events were evaluated for every course according to CTCAE version 3.0. Results: There was no statistically significant difference between the two groups based on any of patient characteristics. No patients complained of persistent Grade 3 infusion reaction. The percentage of Grade 2 or more skin reactions in each course tended to be lower in the TJ-48 group compared with the Control group (TJ-48 group 34% vs control group 57%). Incidence of Grade 2 anorexia in the TJ-48 group was significantly lower than in the Control group (TJ-48 group 34% vs control group 71%, p=0.03). There were no differences regarding tumor response between the two groups. Conclusions: TJ-48 is useful to prevent anorexia in non-resectable or recurrent colorectal cancer patients treated with cetuximab regimen. [Table: see text]
DRES-14. IDENTIFICATION OF CD44 AND ABCC3 AS CHEMOTHERAPY RESISTANT MARKERS FOR GLIOBLASTOMA
Authors: Fengfei Wang
Journal: Neuro-Oncology (2016)

Chemotherapy resistance is a major hindrance in glioblastoma (GBM) management and its mechanism requires further investigation. In this study, we first determined CD44 expression in GBM cell lines and tissues using an R2 platform. We show that CD44 is expressed at similar levels in GBM cell lines and neuron stem cells, and at higher levels in GBM cell lines and recurrent GBMs compared with primary GBMs. Through searching for the CD44-correlated genes in GBMs, we identified ABCC3 as a CD44 highly positive correlated gene. Subsequently, we assessed the levels of CD44, ABCC3, and MGMT (a known marker for Temozolomide sensitivity), in normal brain tissues and GBMs at different stages, as well as the correlation of the levels of these markers with patients' outcome. We reveal that CD44 and ABCC3, not MGMT, are expressed at higher levels in the GBMs than normal counterparts, and elevated levels of CD44 and ABCC3, not MGMT, in GBMs are associated with poor patient outcomes. By evaluating the expression of CD44 and ABCC3 in GBMs with and without p53 mutation or MGMT methylation, we note that CD44 is expressed at higher levels in GBMs with p53 mutation than wild-type, and ABCC3 at higher levels in GBMs with methylated MGMT than those with non-methylated MGMT. We further validated the expression of these markers in GBM cell lines by RT-PCR and noticed higher levels of CD44 and ABCC3 in GBM cells carrying p53 mutations in the DNA binding region than GBM cells without p53 mutation. In addition, we compared the sensitivities among GBM cell lines to two compounds isolated from thunder-god-vine and observed that GBM cells with lower levels of CD44 and ABCC3 had a higher sensitivity to the treatments. Altogether, these findings suggest that elevated levels of CD44 and ABCC3 in GBM are indications of chemotherapy resistance.
Protection Against Vascular Leakage in Vivo by a Peptide Mimetic of the Novel Tethered Ligand Generated by Non-Canonical Cleavage of Protease Activated Receptor 1 by Activated Protein C
Authors: Laurent Burnier, Ranjeet Kumar Sinha, Eveline A. Bouwens, John H. Griffin, Laurent O. Mosnier
Journal: Blood (2012)
A randomized, double-blind, placebo-controlled trial for prevention of oxaliplatin-induced neuropathy symptoms with pregabalin.
Authors: M. Karthaus, C. S. Karapetis, M. Brown, N. Pavlakis, T. Trarbach, N. Marschner, H. A. Duerk, L. Manzione
Journal: Journal of Clinical Oncology (2011)

553 Background: Sensorial peripheral neuropathy (PNP) is a major limitation for pts receiving oxaliplatin-based ctx for CRC. Pregabalin is widely used for treatment of oxaliplatin-induced PNP. We evaluated the efficacy of pregabalin vs. placebo for the prevention of paresthesia from the onset of oxaliplatin-based ctx over each cycle. Methods: Rd, db, placebo-controlled study in adult CRC pts with ECOG 0-2 to undergo a new oxaliplatin/5-FU/FA-based ctx. Pts were excluded if they had neuropathic pain or other of painful paresthesia prior to baseline. Paresthesia, dysesthesia, and pain were rated on a numerical scale (NRS 0-10) every day. Primary endpoint was the time of onset of persistent symptoms (NRS &gt;4). Results: Of the 69 screened pts, 64 were randomized and 61 received study medication (32 pregabalin vs. 29 placebo). Pts were balanced in both arms regarding age, sex, stage, and ctx. There were no differences between both treatment groups for all PNP parameters at any cycle. One pt in both arms developed paresthesia (5.3%) after 9 cycles of ctx, 1 pt had persistent pain (placebo arm). During the follow-up period persistent paresthesic, dysesthesic, and persistent pain developed in 2 vs. 1, 2 vs. 2, and 0 vs. 2 pts, respectively. The study was terminated after a blinded data review found that there were very few events of persistent symptoms, which was then confirmed an interim analysis. Nausea and anorexia were the most frequently reported AE in both groups. Conclusions: The results of this study, which was terminated early at interim analysis, is that too few patients developed persistent symptoms to allow any meaningful treatment difference for prevention of neuropathic pain related to oxaliplatin by pregabalin. There remains an unmet need for oxaliplatin-induced PNP with new trial design issues in this field urgently needed. No significant financial relationships to disclose.
A phase II study for triplet combination of oxaliplatin, irinotecan, and S-1 in patients with metastatic or recurrent gastric cancer
Authors: B. Han, S.R. Park, H.S. Kim, M.-H. Ryu, J.-S. Kim, S.-Y. Rho, B.W. Kang, K.H. Lee, S.Y. Rha, W.K. Kang, Y.-K. Kang, D.Y. Zang
Journal: Annals of Oncology (2016)
A Study of Bedside Visual Art To Decrease Anxiety and Improve Pain and Mood in Cancer Patients: The Mayo Clinic Experience.
Authors: Alexandra P. Wolanskyj, Elizabeth A. Curry, Shawna L. Ehlers, Debra M. Eagle, Dirk R. Larson, Colin L. Colby, Brent A. Bauer, Paul D. Scanlon
Journal: Blood (2007)
Low protracted dose of temozolomide (TMZ) and concurrent radiotherapy for brain metastasis of solid tumors
Authors: R. Addeo, V. Faiola, G. Cennamo, R. Guarrasi, L. Montella, S. Del prete
Journal: Journal of Clinical Oncology (2007)

12525 Background. Whole brain radiotherapy (WBRT) remains the mainstay of therapy for brain metastasis of solid tumours not amenable to surgical resection. Chemotherapy with temozolomide (TMZ) has emerged as an alterative approach for recurrent brain metastases. It has been already used alone or in combination with radiotherapy in the treatment of primary brain tumours. Protracted administration of TMZ, even at relatively low daily doses, leads to significant and prolonged depletion of enzyme O 6 -alkylguaninae-DNA alkyltransferase (AGAT) activity, with may enhance the antitumor activity of the agent. Methods. Patients with histologically or cytologically confirmed breast cancer and NSCLC and inoperable brain metastasis were eligible for the study .We have treated 29 consecutive patients (16 F and 13 M, mean age: 55, range 46–76) affected by brain metastases ( 16 non-small-cell lung cancer and 13 breast cancer) with WBRT at 3 Gy/day administered over a two-week period (on wks 1–2), total dose 30 Gy, and an induction with TMZ 50 mg/m 2 /day during this period, following TMZ 50mg/m 2 fractionated in 21 days every 28 days, for up to 12 cycles. Pts who received at least one cycle of TMZ were assessable for response. Results. Twenty-four patients were subjected to the induction therapy and 124 cycles were performed. TMZ was generally well tolerated, and the main toxicities seen were hematologic. The toxicities were generally between grade 1 or 2 in severity although two patients had grade 3 events. Two CR, in patients with breast cancer and NSCLC. Nine partial responses were recorded in 5/11 patients with breast cancer, 4/13 patients with NSCLC, while a stable disease was achieved in other 5 patients. Eight patients showed progressive BM growth during the treatment. The overall response rate was 45.5% (C.I. 38.7–56.9%), while the disease control rate was 77% (C.I. 61.7–82.4%). At the present, the overall survival at 12 months was 64%. Conclusions. We developed a new regimen based on a different strategy: the utilization of a more intensive TMZ dosing schedule that would permit the concomitant use of a second cytotoxic agent on the primary cancer. Final data analysis will be presented. The schedule was safe and well tolerated and has suggested an encouraging activity in brain metastases. No significant financial relationships to disclose.
A view from New Zealand and an invitation to Sports Physiotherapy New Zealand’s Symposium (14–15 October 2017)
Authors: Hamish Ashton
Journal: British Journal of Sports Medicine (2017)

As a physiotherapist in private practice, I am acutely aware that access to clinically applicable knowledge is not easy in the private practice setting. This is in complete contrast to when we study in our training years and we had university libraries and other resources available to us.

How we use this knowledge differs dramatically too. Back in our student days the library was a source of articles we could access about a topic to complete yet another assignment. Today we need to help us improve our knowledge and thereby improving our treatments and patient outcomes.

When you are not part of a large institution, academic institute or living in a university town, continuing professional education can be …
The Suppressor of Cytokine Signaling-3 Gene Is Overexpressed in Human De Novo Follicular Lymphomas and Promotes IL-3-Independent Proliferation of the BaF3 Pro-B Cell Line.
Authors: Jacqueline C. Barrientos, Sofya Rodov, Arthur W. Zieske, K. Gary J. Vanasse
Journal: Blood (2004)
A phase II study of the proteasome inhibitor PS-341 in patients (pts) with metastatic breast cancer (MBC)
Authors: J. Brown, J. Von Roenn, R. O'Regan, R. Bergan, S. Badve, A. Rademaker, S. Feehan, J. Petersen, M. Patton, W. Gradishar
Journal: Journal of Clinical Oncology (2004)

546 Background: The ubiquitin-proteasome pathway plays an essential role in eukaryotic cellular homeostasis by regulating the degradation of vital intracellular regulatory proteins that govern cell cycle, transcription factor activation and apoptosis. Blocking this proteolytic pathway leads to the elevation of cell cycle inhibitory proteins, including IΚB, whose stabilization results in NF-KB inhibition and ultimately induction of apoptosis. PS-341 (bortezomib, Velcade) is a dipeptide boronic acid derivative that acts as a potent and highly specific inhibitor of the proteasome. PS-341 has demonstrated anti-tumor activity as a single agent in preclinical breast cancer models. Methods: The primary objective of this study was to determine the objective tumor response in pts with MBC receiving PS-341. Eligibility criteria included normal organ/marrow function, measurable disease, performance status (PS) 0–2, absence of brain metastases and ≥ 1 prior chemotherapy regimen for MBC. PS-341 was administered IV, 1.5 mg/m2 on days 1, 4, 8, 11 q 21 days. Dose escalation to 1.7 mg/m2 could be considered in the absence of significant toxicities. Re-evaluation was scheduled q 3 cycles. Results: 12 pts were enrolled for stage-one interim analysis. All 12 pts were evaluable for response. Pt characteristics: median age- 47 years (range 35–64); PS 0/1/2: 6/5/1. Toxicity: grade 4- none; grade 3- pulmonary (2); grade 2- thrombocytopenia (1), diarrhea (1), nausea (3), vomiting (1), pulmonary (4), pain (2), depression (1) and fatigue (2). Response: 1 pt had dose escalation to 1.7 mg/m2 for 1 cycle. Only 3/12 pts completed 3 cycles of therapy (median cycles/pt = 1) and 8/12 pts had disease progression after ≤ 1 cycle of therapy. No objective responses were observed. All 12 patients initially progressed while on therapy and the median time to disease progression was 25 days (range 10–62). At the time of this report, 6 patients have died with a median time to death of 136 days. Conclusions: Single-agent PS-341 does not appear to exhibit significant clinical activity in pts with MBC. This two-stage study was terminated after the first stage due to the absence of any objective response. No significant financial relationships to disclose.
Identification of a Novel Acetyl-CoA Binding Protein (EST1) Which Epigenetically Regulates the Expression of Erythroid-Specific Genes
Authors: Tohru Fujiwara, Tsuyoshi Ikura, Satoshi Ichikawa, Shinichiro Takahashi, Kazumichi Furuyama, Kazuhiko Igarashi, Hideo Harigae
Journal: Blood (2008)