tbuckley/cabot-search huggingface dataset:
IT-30 * ReACT: A PHASE II STUDY OF RINDOPEPIMUT VACCINE (CDX-110) PLUS BEVACIZUMAB IN RELAPSED GLIOBLASTOMA
Authors: D. Reardon, J. Schuster, D. Tran, K. Fink, L. Nabors, G. Li, R. Lukas, A. Desjardins, L. Ashby, J. P. Duic, L. Aneiro, T. Hawthorne, J. Green, M. Yellin, T. Davis, J. Sampson
Journal: Neuro-Oncology (2014)

BACKGROUND: EGFRvIII, a constitutively active tumorigenic EGFR deletion mutation, is linked to poor long-term survival. The investigational vaccine rindopepimut consists of the unique EGFRvIII peptide sequence conjugated to keyhole limpet hemocyanin (KLH), delivered intradermally with GM-CSF. Three phase II studies of rindopepimut in newly diagnosed, resected, EGFRvIII+ glioblastoma have shown encouraging PFS and OS. Bevacizumab (BV), an agent with activity in glioblastoma, may augment EGFRvIII-specific immune response and antitumor activity through inhibition of VEGF and its immunosuppressive properties. METHODS: "ReACT" is a Phase II study of rindopepimut plus BV in patients with 1st or 2nd relapse of EGFRvIII+ glioblastoma. BV-naïve pts (Group 1; n = 70) are randomized 1:1 to BV plus double-blinded injection of either rindopepimut or control (KLH). BV-refractory patients (progression within 2 months of BV; Group 2/2C, n = 98) receive BV plus open-label rindopepimut. RESULTS: 234/700 (33%) screened patients are EGFRvIII+. 115 patients (Group 1 = 72, Group 2/2C = 43) are enrolled. Primary toxicity is Grade 1-2 injection site reaction. In group 1, for rindopepimut + BV vs. KLH + BV, objective response rate (ORR; investigator-assessed, RANO criteria) is 23% (6/26) vs 12% (3/25) [35% vs. 20% including responses observed at a single time point ("unconfirmed")]. In Group 2/2C (evaluable n = 30), one unconfirmed PR and one sustained PR (patient continues treatment at 15 months) occurred. Two additional patients had pre-study progression >2 months after BV; one maintained a CR for 11.1 months (peak anti-EGFRvIII titer = 1:3,276,800), while the second experienced an unconfirmed CR. Median peak rindopepimut-induced anti-EGFRvIII humoral response is 1:25,600 [range <1:100-1:6,553,600]). Rapid titer generation was associated with prolonged OS (Group 2: p = 0.01). CONCLUSIONS: Rindopepimut + BV has induced potent EGFRvIII-specific immune response and tumor regression in immunosuppressed recurrent glioblastoma patients naive or refractory to BV. Full response, PFS and OS data are expected to further define the potential clinical benefit of the combination in relapsed glioblastoma.
NI-61 * VOLUMETRIC H-1 MR METABOLIC IMAGING FOR DEFINITION OF LESION BURDEN AND PREDICTION OF OUTCOME FOR PATIENTS WITH NEWLY DIAGNOSED GBM
Authors: S. Nelson, Y. Li, M. Prados, N. Butowski, J. Clarke, S. Chang
Journal: Neuro-Oncology (2014)

Interpretation of the efficacy of novel therapies for patients with GBM with anatomic MR imaging is complicated by pseudo-progression and pseudo-response. The goal of this study was to obtain volumetric H-1 MRSI data with a rapid 3-D PRESS lactate edited EPSI sequence (Tacq = 10 minutes) at pre- and post-RT scans in order to evaluate the biological properties of the lesion and relate them to overall survival (OS). The population comprised 58 patients with newly diagnosed GBM: 35 received radiation (RT), Temozolomide (TMZ) and Enzastaurin (Group 1) and 24 received RT, TMZ, Tarceva and Bevacizumab (Group 2). The T2L and CEL were defined from the anatomic images and the choline to NAA index (CNI) and normalized levels of lactate (nLac) estimated for each voxel from the MRSI data. Age adjusted Cox Proportional Hazards models were applied to assess the association of these parameters OS (P < 0.05 being considered significant). From pre-RT to post-RT, the median volume of the CEL decreased by 49% for Group 1 and by 42% for Group 2. The median volume of the T2L was relatively stable for patients in Group 1 (median 20.9 to 19.5cc) but decreased with follow-up for patients in Group 2 (median 23.8 to 5.5cc). The maximum CNI within the T2L decreased more for Group 1 (median 9.7 to 5.9) than for Group 2 (median 6.4 to 5.2). Levels of nLac within the T2L at pre- and post-RT scans were significantly associated with OS for both Groups. These findings demonstrate the feasibility of obtaining rapid, volumetric H-1 MRSI data that provide distinct measures of lesion burden and that are associated with OS. Integration of these metrics into the evaluation of novel therapies is likely to be important for resolving ambiguities associated with anatomic imaging methods.
Abstract LB-154: Anti-tumor effect of dendritic cell-based immunotherapy in the patients with advanced breast cancer.
Authors: Shinichiro Akiyama, Hiroyasu Yasuda, Hiroyuki Abe
Journal: Cancer Research (2011)

Abstract Background and objective: Tumor-specific cytotoxic T lymphocytes (CTLs) can be activated in vivo by dendritic cell (DC)-based vaccination. However, clinical responses to the immunotherapy with DC vaccination have only been observed in a minority of patients with solid cancer. In the current study, the clinical efficacy of the DC vaccine pulsed with the peptide derived from breast cancer-associated antigens has been evaluated in the patients with advanced, inoperable breast cancer. Patients and Methods: 21patients with advanced, inoperable breast cancer refractory to standard treatment were entered the study. DCs which were generated from CD14+ monocytes from leukapheresis by 6-day cultivation with granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin (IL)-4, were matured by OK-432, a streptococcal agent, and were pulsed with the pancreatic cancer-associated antigens, such as WT1, MUC1. These DCs (1 × 107) were intradermally administered more than 5 times at 14-day intervals. Results: Of the 21 patients, complete response (CR) was observed in 0 (0%), partial response (PR) in 2 (9.6%), stable disease (SD) in 7 (33.3%), progressive disease (PD) in 12 (57.1%). Response rate was 9.6%. Tumor control rate was 42.9%. Mean survival time after DC therapy was 514days. Severe side effects of more than grade 3 which were assessed in accordance with NCI-Common Toxicity Criteria v.2.0, were not observed. Conclusions: It was strongly suggested that the DC vaccination pulsed with cancer associated-peptides was safety and effective in the patients with the inoperable breast cancer refractory to standard treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-154. doi:10.1158/1538-7445.AM2011-LB-154
Hepatic Iron Concentration and Total Body Iron Stores in Thalassemia Major
Authors: Emanuele Angelucci, Gary M. Brittenham, Christine E. McLaren, Marta Ripalti, Donatella Baronciani, Claudio Giardini, Maria Galimberti, Paola Polchi, Guido Lucarelli
Journal: New England Journal of Medicine (2000)

We tested the usefulness of measuring the hepatic iron concentration to evaluate total body iron stores in patients who had been cured of thalassemia major by bone marrow transplantation and who were undergoing phlebotomy treatment to remove excess iron.
Abstract 13699: Cardiovascular Health Impact of Air Pollution Control in Beijing and Urban China: Projections From the Cardiovascular Disease Policy Model-China
Authors: Chen Huang, Andrew E Moran, Xueli Yang, Jie Cao, Kai Chen, Miao Wang, Jiang He, Lee Goldman, Pamela G Coxson, Dong Zhao, Patrick L Kinney, Dongfeng Gu
Journal: Circulation (2015)

Background: Air pollution ranks the 4th among risk factors responsible for China’s avoidable disease burden. We projected the potential cardiovascular health benefits achievable with sustained air quality improvement in Beijing and all of urban China. Methods: Coronary heart disease (CHD) and stroke mortality and life years gained were projected in adults aged 35-84 years in Beijing and urban China using the Cardiovascular Disease Policy Model-China. We simulated two air quality improvement scenarios from 2015-2030, each achieved gradually over 10 years: 1) the 2008 Beijing Olympics fine particle matter (PM2.5) level of 55 μg/m3, and 2) the World Health Organization (WHO) recommendation of 10 μg/m3. For comparison, we simulated a 50% reduction in active and secondhand smoking and reduction of systolic hypertension to 140 mmHg, each over 5 years. Relative risks of CHD, stroke and all-cause mortality associated with long term PM2.5 exposure were obtained from a meta-analysis of observational studies. Systolic blood pressure and smoking relative risks were estimated from China Multi-provincial Cohort Study. Results: PM2.5 reduction to 2008 Olympic levels in Beijing would reduce stroke deaths by 2.7%, CHD deaths by 7.2% over 2015-2030 and would gain life-years on the order of about a third of that projected for a 50% smoking reduction, and a fourth of that projected for systolic hypertension control (Table). However, achieving more aggressive WHO PM2.5 goal would yield greater life year gains than either tobacco or systolic blood pressure control. Achieving 2008 Olympics levels in urban China would prevent 304,000 stroke deaths, 619,000 CHD deaths, and gain 4.2 million life years over 2015-2030. Conclusions: Air pollution is a leading cardiovascular risk factor in Beijing and all urban China. We projected that lowering air pollution to Beijing Olympics level could prevent about 900,000 cardiovascular deaths and gain about 4.2 million life years in urban China by 2030.
Abstract 1327: Study the effect of IGFBP5 in human fibroblast cells
Authors: Hsin-Ying Lin, Cheng-Ying Shen, Liang-Chuan Lai, Eric Y. Chuang, Mong-Hsun Tsai
Journal: Cancer Research (2010)

Abstract Retinoblastoma (Rb) is a rapidly developing cancer which develops in the cells of the retina, the light detecting tissue of the eye. It is the most common primary ocular malignancy (eye cancer) of childhood. There are both hereditary and sporadic forms of retinoblastoma. The hereditary form of retinoblastoma is associated with a germ line mutation in one of the RB genes and is characterized by the occurrence of multiple, bilateral Rb tumors and a predisposition to the development of second cancers. These second tumors often occur in patients treated by radiation therapy. In the previous study, an unexpected hypersensitivity to ionizing radiation in skin fibroblasts derived from unaffected parents of children with hereditary Rb was observed. By use of the prediction analysis for microarrays (PAM) and principal component analysis (PCA), 42 significantly differential expressed genes were selected and identified as radiosensitive genes. Therefore, one of these 42 genes, IGFBP5 (insulin-like growth factor binding protein 5) was chosen to further investigate the role in radiosensitivity in fibroblast cells. IGFBP5 was overexpressed or knocked down in HS68 (the human foreskin fibroblast) cells. The cells were irradiated with γ -ray, and then counted and seeded into the plates for colony formation assays. According to the results, IGFBP5-ovexpressed cells seemed to be more resistant to radiation. Also, IGFBP5 knocked down cells might be more sensitive to radiation under low dose of radiation. In summary, these results suggested that IGFBP5 may play a role in radiosensitivity in human fibroblast cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1327.
Ixabepilone plus capecitabine improves progression free survival in patients with metastatic breast cancer resistant to taxanes: a pooled analysis from two phase III trials.
Authors: H Roche, R Li, J Ro, E Vrdoljak, ZU Rahman, C Medina, P Conte, LA Volles, V Poulart, JA Sparano
Journal: Cancer Research (2009)

Abstract Abstract #2015 Background:&amp;#x2028; Patients (pts) with MBC whose tumors are resistant to taxanes (T) have limited therapeutic options. Ixabepilone (ixa), the first in a new class of antineoplastic agents, showed clinical benefit in combination with capecitabine (C) in 2 large clinical trials in metastatic breast cancer (MBC) pts resistant to (study 046, JCO, 2007), or pretreated with anthracycline (A) and T (study 048). Pts whose tumors were resistant to A/T were also allowed to enter the 048 trial. In 048, ixa + C, compared to C alone, also demonstrated significant increases in progression-free survival (PFS, HR 0.79 [0.69-0.90)]) and ORR (43% vs 29%). A trend toward increased OS was seen both in 048 (HR 0.90 [0.78-1.03]) and in 046 (HR 0.90 [0.77-1.05]), which did not reach statistical significance. Here we present a pooled analysis from the 2 studies of clinical outcomes (ORR, PFS, and OS) in patients with a strict definition of resistance to T.&amp;#x2028; Methods:&amp;#x2028; 1973 pts with MBC previously treated with an A and T, were randomized in phase III trials to receive either ixa (40 mg/m2 IV over 3h Q3w) + C (1000 mg/m2 PO BID x14d Q3w) or C alone (1250 mg/m2 PO BID x14d Q3w). For both studies, resistance was defined as disease progression up to 4 months following T in the metastatic setting and up to 12 months following adjuvant T therapy. Due to the similarity of the study populations, individual pt data from both studies was pooled to better evaluate treatment effect within pre-planned patient subgroups.&amp;#x2028; Results:&amp;#x2028; 1337 pts from the 2 studies were T resistant and randomized to ixa + C or C alone. ORR and PFS favored ixa + C in this pt population, and there was a trend towards increased OS, which did not reach statistical significance (see table).&amp;#x2028; &amp;#x2028; Conclusion:&amp;#x2028; Ixa + C is the first combination to show a clinical benefit of PFS in pts with MBC resistant to T (following a strict definition of resistance). The benefit seen in this pooled analysis was consistent with that observed in the resistant pt population from the individual studies as well. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2015.
Responder Analysis Evaluating the Effect of Budesonide/Formoterol Pressurized Metered-Dose Inhaler (BUD/FM pMDI) in Patients with Moderate to Severe Asthma with Versus without Fixed Airflow Obstruction (FAO)
Authors: Donald P. Tashkin, Bradley E. Chipps, Tom Uryniak, Frank Trudo
Journal: Journal of Allergy and Clinical Immunology (2013)
A Familial Defect in Platelet Function Associated with Impaired Release of Adenosine Diphosphate
Authors: Harvey J. Weiss, Paul A. Chervenick, Ralph Zalusky, Arthur Factor
Journal: New England Journal of Medicine (1969)

Abnormalities of platelet function in some patients with primary, but sporadic, disorders of hemostasis have been attributed to impaired release of platelet adenosine diphosphate (ADP). This defect was detected in six affected members of a family, in association with a slightly prolonged bleeding time. As a consequence, platelet aggregation induced by connective tissue (collagen) and kaolin-induced platelet factor 3 release were impaired, and the second wave of epinephrine-induced aggregation was absent. Primary aggregation by ADP at ambient temperature was normal, but the platelets disaggregated rapidly at 37°C. The platelet defect appears to have been transmitted as an autosomal dominant, with variable expressivity, through three generations. Besides being functionally defective, the platelets were smaller than normal and contained reduced amounts of adenosine triphosphate (ATP) and ADP. A population of prematurely senescent platelets may be present in these patients.
Familial Hyperprolinemia, Cerebral Dysfunction and Renal Anomalies Occurring in a Family with Hereditary Nephropathy and Deafness
Authors: Irwin A. Schafer, Charles R. Scriver, Mary L. Efron
Journal: New England Journal of Medicine (1962)

This report presents clinical, genetic and biochemical studies of a family with cerebral dysfunction, congenital renal anomalies and a defect in the metabolism of the amino acid L-proline. In addition, certain family members have microscopic hematuria or nerve deafness or both.A hereditary nephropathy characterized by hematuria or pyelonephritis, or both, with nerve deafness, has been documented in at least 13 families.1 2 3 Cerebral dysfunction, renal malformations or a defect in amino acid metabolism has not previously been described in association with this syndrome.Clinical Summary of the Index CaseThe family was brought to our attention when F.M. (IV:D5), a . . .
Abstract 3347: A proneural signature profile predicts response to Notch inhibition in glioma stem cells
Authors: Norihiko Saito, Jun Fu, Jun Yao, Roel GW Verhaak, Dimpy Koul, W.K. Alfred Yung
Journal: Cancer Research (2012)

Abstract The Cancer Genome Atlas Network described genomic abnormalities and gene expression-based molecular subtypes of GBM that showed a strong relationship between subtypes, genomic alterations and different neural lineages. Future studies are required to elucidate the intricate relationship between tumor subtypes and treatment response. We have thus embarked on a comprehensive effort to detecting expression signatures that are associated with response to the therapy and these signatures may allow prospective selection of patients with high likelihood of responding to therapy. Notch signaling pathway is an evolutionarily conserved pathway that plays an important role in multiple cellular and developmental processes including cell fate decision, differentiation, proliferation, survival, angiogenesis and migration. Recent studies indicate that the Notch signaling pathway regulates normal stem cells in the brain, and glioma stem Cells (GSCs) with high Notch activity. We investigated the effects of Notch pathway inhibition on GSCs growth using commercially available inhibitors. Drug cytotoxicity test on 16 GSCs show differential growth response to Notch inhibitors stratifying GSCs into two groups: responders (6 cell lines) vs non-responders (10 cell lines). Gene expression clustering identified a responder gene signature enriched in 1: proneural genes such as Olig2, Sox-9, NKX2-2, and 2: Notch signaling component such as Notch-1, Notch-3, Hes-3 and Hes-5. These signature were validated by western blot analysis. Treatment with Notch inhibitors reduced neurosphere formation in vitro accompanied with attenuated Notch intracellular domain (NICD), Hes-1, Hes-3, and Hes-5. In addition, the expression of nestin-the stem cell marker was reduced and an increased expression of lineage differentiation markers TuJ1 and GFAP was observed following Notch inhibition. In conclusion, we have identified a responder signature for a group of glioma stem cells that can be targeted by Notch inhibitors and this may allow the selection of patients with high likelihood of responding to this therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3347. doi:1538-7445.AM2012-3347
RISK FACTORS OF ADVERSE EVENTS FOLLOWING SURGERY AMONG PATIENTS TREATED WITH CORONARY DRUG-ELUTING STENT IMPLANTATION
Authors: Gro Egholm, Steen Kristensen, Troels Thim, Kevin K.W. Olesen, Morten Madsen, Henrik T. Sørensen, Svend Eggert Jensen, Lisette Jensen, Hans Erik Bøtker, Michael Maeng
Journal: Journal of the American College of Cardiology (2016)
Computed tomography in the diagnosis and staging of cholangiocarcinoma and pancreatic carcinoma
Authors: P C Freeny
Journal: Annals of Oncology (1999)

This paper is a review of the current techniques and results of helical CT in the diagnosis and staging of pancreatic adenocarcinoma and cholangiocarcinoma of the intra and extrahepatic biliary ducts. CT has a diagnostic accuracy rate of over 95% for detection and diagnosis of pancreatic carcinoma and close to 100% in staging unresectable tumors. The accuracy of staging surgically resectable tumors is about 80%. Accuracy of determining the level of biliary obstruction caused by cholangiocarcinoma is close to 100%. The accuracy of making a specific diagnosis is about 78%.
Abstract 3491: Chromosome 14q loss leads to haploinssuficiency of HIF-1a and poor outcomes in metastatic clear cell renal cell carcinoma
Authors: Federico A. Monzon, Karla Alvarez, Leif Peterson, Nizar Tannir, Eric Jonasch
Journal: Cancer Research (2011)

Abstract Purpose – One of the current key dilemmas in the management of metastatic renal cell carcinoma (mRCC) is the manifestation of innate or acquired resistance to anti-angiogenic therapy. Currently there are no biomarkers of therapeutic efficacy for antiangiogenic agents in clear cell renal cell carcinoma (ccRCC). Loss of chromosomal arm 14q has been previously associated with poor outcomes in surgically treated patients. We evaluated the association between 14q loss and therapeutic resistance in metastatic ccRCC (mRCC) and explored the role of candidate effector genes on this chromosome. Experimental Design – DNA from archival FFPE tumor specimens from 56 mRCC patients treated with sorafenib or bevacizumab was analyzed with Affymetrix 250K Nsp SNP microarrays. We identified the presence of genomic imbalances focusing on the presence of 14q loss. We then evaluated candidate genes in chromosome 14 by qPCR and immunohistochemistry (IHC) in the bevacizumab treated cohort. Results – 14q loss showed a significant association with worse response (SDPD vs. CRPR) in bevacizumab cohort (Fisher's exact test, p=0.0473), and with shorter progression free survival (PFS) in the sorafenib cohort (p=0.0318). HIF1A mRNA expression was significantly reduced in specimens with loss of 14q and was associated with PFS in the bevacizumab treated cohort (p=0.045). HIF-1alpha protein expression was also reduced in samples with 14q loss. Conclusions – Our studies demonstrate an association between a specific chromosomal alteration (14q loss) and clinical outcome in patients with advanced renal cell carcinoma treated with antiangiogenic agents. Loss of 14q was also associated to changes in the expression of HIF1A. Low HIF1A expression was strongly correlated with shorter PFS. We hypothesize that loss of 14q could lead to an imbalance in HIF-1α/HIF-2α activity, leading to increased HIF-2α, which has been shown to improve tumor cell viability by upregulating various pro-survival pathways. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3491. doi:10.1158/1538-7445.AM2011-3491