tbuckley/cabot-search huggingface dataset:
Meta-analysis of 59 gene expression based biomarker candidates predicting survival after tamoxifen treatment in breast cancer.
Authors: Balazs Gyorffy, Mate Kormos, Andras Lanczky, Zsuzsanna Mihaly
Journal: Journal of Clinical Oncology (2013)

e11564 Background: To date, three molecular markers (ER, PR and CYP2D6) have been used in clinical setting to predict the benefit of the anti-estrogen tamoxifen therapy. Our aim was to validate new biomarker candidates predicting response to tamoxifen treatment by evaluating these in a meta-analysis of available microarray datasets with known treatment and follow-up. Methods: Biomarker candidates were identified in Pubmed 2007-2012 and in the 2010-2012 ASCO and SABCS abstracts. Breast cancer microarray datasets were downloaded from GEO and EGA. Of the biomarker candidates, only those identified or already validated in a clinical cohort were included. In the transcriptomic datasets, only patients with tamoxifen treatment for relapse-free survival and endocrine treatment for overall survival were eligible. The raw microarray data was re-processed and integrated into two databases. Relapse free survival (RFS) up to 5 years was used as endpoint in a ROC analysis in the GEO datasets. In the EGA dataset, Kaplan-Meier analysis was performed for overall survival (OS). Statistical significance was set at p&lt;0.01. Results: The transcriptomic datasets included 667 GEO-based and 1208 EGA-based patient samples. All together 59 biomarker candidates were identified. Of these, the best performing genes were PGR (AUC=0.64, p=2.3E-07), MAPT (AUC=0.62, p=7.8E-05), SLC7A5 (AUC=0.62, p=9.2E-05) and TP53 (AUC=0.60, p=1.2E-03). Further genes significantly correlated to relapse-free survival include BTG2, HOXB7, DRG1, CXCL10, BCL2, TPM4, IGF1R and SMC3. Correlation to overall survival was significant for PGR (HR=0.67, p=1.7E-04), MAPT (HR=0.7, p=7.2E-04) and SLC7A5 (HR=1.6, p=1.6E-05). None of the remaining genes including ESR1 reached statistical significance for relapse-free survival. Conclusions: We validated two genes (MAPT and SLC7A5) as being capable to select those patients most likely benefit from tamoxifen treatment.
Identifying patients with non-small cell lung cancer (NSCLC) unlikely to benefit from erlotinib: An exploratory analysis of National Cancer of Institute of Canada Clinical Trials Group BR.21
Authors: M. Florescu, B. Hasan, F. A. Shepherd, L. Seymour, K. Ding, J. Pater
Journal: Journal of Clinical Oncology (2006)

7161 Background: Despite a 9% response rate, BR.21 demonstrated significant survival benefit for patients receiving erlotinib as 2nd/3rd line therapy for NSCLC. We undertook to characterize, by exploratory subset analysis, patients less likely to benefit from erlotinib. To identify factors for consideration, we first identified baseline characteristics associated with early progression by eight wks and early death by 3 mos. Methods: Using stratification factors and potential prognostic factors from BR.21, the Cox regression model with stepwise selection was used to establish a prognostic model to separate erlotinib patients into 4 risk categories based on the 10th, 50th &amp; 90th percentiles of prognostic index scores. 7 variables (smoking history, PS, weight loss, anemia, high LDH, response to prior chemo and time from diagnosis to randomization) were used in the final model. The hypothesis was that the characteristics of the treated patients in the highest risk group would also be predictive of lack of benefit from erlotinib when erlotinib and placebo patients with the same characteristics were compared. Results: Factors associated with PD by 8 wks were: PS2–3 (p = 0.009), weight loss (p = 0.0004), anemia (p = 0.008), PD to prior chemo (p = 0.006), non-Asian (p = 0.047), EGFR IHC-negative (p = 0.005), Factors associated with survival &lt; 3 mos were: PS2–3 (p &lt; 0.0001), weight loss (p &lt; 0.0001), anemia (p &lt; 0.0001), PD to prior chemo (p &lt; 0.0001), non-Asian (p = 0.008), high LDH (p &lt; 0.0001), time to randomization &lt;12 mos (p = 0.0003). Comparison of overall survival for the 4 risk groups derived from prognostic index score as follows: high benefit (HR = 0.41, p = 0.007), 2 intermediate benefit (HR 0.79, p = 0.09; HR 0.80; p = 0.09); no benefit (HR 1.23; p = 0.42). Median survivals for erlotinib (placebo) patients in each group were 17.3 (8.3), 9.7 (7.5), 4.1 (3.7), 1.9 (2.7) mos. Conclusions: By establishing a prognostic model, we identified a small group of patients who are unlikely to benefit from 2nd/3rd line erlotinib therapy. This model requires prospective validation to confirm that it is both prognostic and predictive of outcome from treatment. [Table: see text]
An Injectable Strong Hydrogel for Bone Reconstruction
Authors: Yanran Zhao, Zhiyong Cui, Bingchuan Liu, Junfeng Xiang, Dong Qiu, Yun Tian, Xiaozhong Qu, Zhenzhong Yang
Journal: Advanced Healthcare Materials (2019)

Abstract For treating bone defects in periarticular fractures, there is a lack of biomaterial with injectable characteristics, tough structure, and osteogenic capacity for providing a whole‐structure support and osteogenesis in the defect area. An injectable hydrogel is an ideal implant, however is weak as load‐bearing scaffolds. Herein, a new strategy, i.e., an in situ formation of “active” composite double network (DN), is raised for the preparation of an injectable strong hydrogel particularly against compression. As a demonstration, 4‐carboxyphenylboronic acid grafted poly(vinyl alcohol) (PVA) is crosslinked using calcium ions to provide a tough frame while bioactive glass (BG) microspheres are associated by poly(ethylene glycol) to obtain an interpenetrated inorganic network for reinforcement. The injected PVA/BG DN hydrogel gains compressive strength, modulus, and fracture energy of 34 MPa, 0.8 MPa, and 40 kJ m −2 , respectively. Then, the properties can be “autostrengthened” to 57 MPa, 2 MPa, and 65 kJ m −2 by mineralization in 14 days. In vivo experiments prove that the injected DN hydrogel is more efficient to treat femoral supracondylar bone defects than the implanted bulk DN gel. The work suggests a facile way to obtain a strong hydrogel with injectability, cytocompatibility, and tailorable functionality.
Efficacy and Toxicity of Donor Lymphocyte Infusions in Relapsed Acute Myeloid Leukemia Post Allogeneic Hematopoietic Cell Transplantation: Single-Center Experience
Authors: Ioanna Sakellari, Varnavas Konstantinou, Eleni Gavriilaki, Despina Mallouri, Ioannis Batsis, Vassiliki Kalaitzidou, Chrysa Apostolou, Maria Kaliou, Anastasia Bouinta, Christos Smias, Panayotis Kaloyannidis, Damianos Sotiropoulos, Evangelia Yannaki, Achilles Anagnostopoulos
Journal: Blood (2016)
NKp46 Is a Useful Diagnostic Biomarker in Gastrointestinal T-Cell Lymphoproliferative Diseases and Constitutes a Therapeutic Target. a Celac Network Study
Authors: Morgane Cheminant, Julie Bruneau, Georgia Malamut, David Sibon, Nicolas Guegan, Sascha Cording, Amélie Trinquand, Nicole Brousse, Sherine Khater, Elizabeth A. Macintyre, Vahid Asnafi, Laurent Pouyet, Florence Lhospice, Thierry Jo Molina, Bertrand Meresse, Christophe Cellier, Nadine Cerf-Bensussan, Olivier Hermine
Journal: Blood (2017)
Factors that predict successful remobilization after autologous hematopoietic progenitor cell transplant (aHCT) for multiple myeloma.
Authors: Xenofon Dimitrios Papanikolaou, Eric Rosenbaum, Lisa Tyler, Bart Barlogie, Michele Cottler-Fox
Journal: Journal of Clinical Oncology (2013)

8610 Background: aHCT is a proven therapeutic modality in treating relapsed multiple myeloma (MM). However, previously transplanted patients may have no hematopoietic progenitor cells (HPC) left in storage. Methods: Collection of HPC after aHCT was studied in 221 MM patients who underwent 333 mobilization attempts between 10/2000 and 06/2012. Results: The median number of CD34+ collected was 4.7 ×10 6 /kg, with 74% of collections yielding at least 2.5×10 6 /kg. Mobilization with chemotherapy and G-CSF was most efficient, yielding a median of 6.84×10 6 /kg (p&lt;0.001). Growth factor-only mobilization was least effective, with a median of 3.01×10 6 /kg (p&lt;0.001). The addition of plerixafor yielded a significant increase if there was a previous “poor” (&lt;2.5×10 6 /kg) collection (1.83 vs. 3.43×10 6 /kg, p&lt;0.001). In univariate statistical analysis female sex (p=0.048), platelets (PLT) ≤100×10 6 /L (p&lt;0.001), hemoglobin ≤11g/dL (p=0.032), and albumin ≤3.5 g/dL (p=0.003) prior to mobilization correlated with a “poor” collection. In multivariate analysis only PLT ≤100×10 6 /L was significant (p&lt;0.001). Of the 221 patients collected, 154 underwent subsequent aHCT. Infusion of HPC procured after previous aHCT did not yield a difference in treatment-related mortality (p=0.766). Use of only cells collected after aHCT was related to a delayed platelet engraftment ≥50×10 6 /L (p&lt;0.001). Conclusions: Remobilization and collection of an adequate number of HPC after previous aHCT is feasible. PLT ≤100×10 6 /L suggest the need for plerixafor for a successful collection. Infusion of the graft procured is safe and effective, but use of only cells collected after aHCT is associated with delayed platelet engraftment &gt;50×10 6 /L.
Mutational processes contributing to the development of multiple myeloma
Authors: Phuc H. Hoang, Alex J. Cornish, Sara E. Dobbins, Martin Kaiser, Richard S. Houlston
Journal: Blood Cancer Journal (2019)

Abstract To gain insight into multiple myeloma (MM) tumorigenesis, we analyzed the mutational signatures in 874 whole-exome and 850 whole-genome data from the CoMMpass Study. We identified that coding and non-coding regions are differentially dominated by distinct single-nucleotide variant (SNV) mutational signatures, as well as five de novo structural rearrangement signatures. Mutational signatures reflective of different principle mutational processes—aging, defective DNA repair, and apolipoprotein B editing complex (APOBEC)/activation-induced deaminase activity—characterize MM. These mutational signatures show evidence of subgroup specificity—APOBEC-attributed signatures associated with MAF translocation t(14;16) and t(14;20) MM; potentially DNA repair deficiency with t(11;14) and t(4;14); and aging with hyperdiploidy. Mutational signatures beyond that associated with APOBEC are independent of established prognostic markers and appear to have relevance to predicting high-risk MM.
Preoperative serum vascular endothelial growth factor as a prognostic parameter in ovarian cancer
Authors: A. Reinthaller, P. Sevelda, L. A. Hefler
Journal: Journal of Clinical Oncology (2006)

10093 Objective: Serum vascular endothelial growth factor (VEGF) levels have been shown to be associated with an adverse outcome in patients with ovarian cancer. We studied the clinical value of serum VEGF as an independent prognostic parameter. Methods: In the present study, we ascertained preoperative serum VEGF in a series of 314 patients with ovarian cancer. VEGF serum were evaluated in 45 new cases. Serum VEGF was evaluated prior to primary surgery in all patients. The re-analysis of previously published data comprised a total of 269 cases. Patients were treated between 1990 and 2003. Mean duration of follow-up was 38.9 (32.4) months. Patients with epithelial ovarian cancer were included into the present study, patients with other malignant ovarian tumors, borderline tumors, and benign adnexal masses were excluded. Serum VEGF was evaluated prior to primary surgery using an enzyme linked immunosorbent assay (Quantikine Human VEGF Immunoassay; R&amp;D Systems, Minneapolis, MN) in all studies. Results were correlated with clinical data. Results: Median serum VEGF was 407 (238–746) pg/mL. Serum VEGF was associated with serum CA 125 (p=0.003) and residual tumor mass (p=0.02; residual tumor mass &lt; 1cm: 375.5 [209.5–608.9] pg/mL vs. residual tumor mass ≥ 1cm: 625.2 [320.7–1046.7] pg/mL). Serum VEGF was not associated with FIGO stage (p=0.5), lymph node involvement (p=0.2), tumor grade (p=0.2), and patients’ age (p=0.08). In a univariate Kaplan-Meier analysis, FIGO stage, residual tumor mass, tumor grade, patients’ age, serum CA 125, and preoperative serum VEGF were associated with overall survival. In a multivariate Cox regression model, higher FIGO stage, presence of residual tumor mass after primary surgery, and higher serum VEGF were independently associated with a shortened overall survival. Planned subgroup analysis was performed for patients with ovarian cancer FIGO stage I. In a multivariate Cox regression model, higher tumor grade and higher serum VEGF were the only independent prognosticators for overall survival. Patients with FIGO stage I ovarian cancer and a serum VEGF ≥ 380 pg/mL had a 8-fold increased risk for experiencing cancer related death. Conclusion: Serum VEGF is an independent prognostic parameter in patients with all stages of ovarian cancer. No significant financial relationships to disclose.
Abstract 15607: Effect of Short-Term Fasting on Electrocardiographic Parameters
Authors: Willeke van der Stuijt, Pim Gal, Michiel J Kemme, Jacobus Burggraaf
Journal: Circulation (2018)

Introduction: Electrocardiograms (ECGs) of healthy volunteers are frequently evaluated during early clinical drug development trials to screen for possible cardiac adverse reactions. Volunteers are...
Bone marrow CX3CR1+ mononuclear cells relay a systemic microbiota signal to control hematopoietic progenitors in mice
Authors: Seungwon Lee, Hyekang Kim, Gihoon You, Young-Min Kim, Seunghun Lee, Viet-Hoan Le, Ohseop Kwon, Sin-Hyeog Im, You-Me Kim, Kwang Soon Kim, Young Chul Sung, Ki Hean Kim, Charles D. Surh, Yunji Park, Seung-Woo Lee
Journal: Blood (2019)
Adoptive immunotherapy plus cryotherapy in murine model of metastatic colon cancer
Authors: M. Y. Levy, H. Symons, W. Chowdhury, R. Rodriguez, E. Fuchs
Journal: Journal of Clinical Oncology (2006)

2520 Background: Cryotherapy provides a known local treatment effect for cancer. Additionally, many reports suggest that preservation of tumor antigens in the cryoablation (cryo) treatment site may lead to a systemic immune response that may treat remote tumor. However, the capacity of cryo to induce a regression of metastatic lesions may be limited by tumor-induced alterations of the immune system, including tumor-specific T cell tolerance and suppression. One method of awakening dormant anti-tumor immunity is by treating cancer-bearing animals with cyclophosphamide (Cy), to eliminate suppressor T cells, and allogeneic donor lymphocyte infusion (DLI), to provide an exogenous source of CD4 + T cell help for endogenous, tumor-specific CD8 + T cells. We therefore asked whether Cy ± DLI could augment the anti-tumor effect of cryo in a mouse metastatic colon cancer model. Methods: BALB-C mice were inoculated on d0 with the 10 6 syngeneic CT-26 SQ to generate local tumor and 10 5 IV via tail vein injection to generate lung metastases. The SQ tumor was then treated on d14 with either surgical excision or cryo, and mice were treated further with nothing, Cy alone (200 mg/kg IP on d13), or Cy plus CD8 + T cell-depleted DLI from allogeneic donors. At d102, surviving animals were re-challenged with 10 5 CT-26 cells IV. 5 previously untreated BALB-C controls were injected at the same time with 10 5 CT-26 IV. Results: Our data demonstrates a survival advantage of mice treated with Cy plus cryo (med. survival 100.5 days) compared to animals treated with Cy + surgery (med. survival 33d; p = .002). Furthermore, a significant (p = .0006) effect of the adoptive immunotherapy was seen with a comparison between the surgery +Cy group (med. survival 33d), and the surgery +Cy/DLI group (med. survival 60d). There are currently 6/18 mice alive at d143 that received cryo + Cy±DLI. In the re-challenge experiment, all control animals died of tumor by d19 with a med. survival of d18. 6/7 re-treated animals remain alive and free of tumor 41d after tumor re-challenge (p = .0041). Conclusions: These results suggest a systemic immune effect on distant metastases may occur after local cryo when cryo is coupled with Cy alone and Cy+DLI. The results from this experiment warrant further characterization of the mechanisms for the anti-tumor effects observed. No significant financial relationships to disclose.
Phase II study of preoperative panitumumab, 5-fluorouracil, and oxaliplatin with concurrent radiotherapy in locally advanced rectal cancer: Preliminary safety results (StarPan /STAR-02 Study)
Authors: C. Pinto, F. Di Fabio, E. Maiello, P. Di Tullio, S. Pini, C. Aschele, C. Garufi, A. Bochicchio, G. Pinotti, T. Latiano, A. Martoni
Journal: Journal of Clinical Oncology (2009)

4110 Background: The aim of this phase II study is to assess the activity of preoperative external radiotherapy combined with panitumumab, oxaliplatin and 5-fluorouracil in locally advanced rectal cancer patients (pts). Methods: Pts entering the study had histologically-proven rectal adenocarcinoma, either uT3N+ or T4 N-/+ stage, with location &lt;12 cm from the anal margin. Panitumumab was administered at a dose of 6 mg/kg IV, 2 weeks before the start of chemoradiotherapy, and then in combination with chemoradiotherapy, every 2 weeks for 3 times. 5-fluorouracil and oxaliplatin were administered according to an established schedule of STAR-01 Study (oxaliplatin 60 mg/m 2 IV weekly for six times, and 5- fluorouracil 225 mg/m 2 /day continuous infusion IV d 1–38). Radiotherapy was delivered up to a dose of 50.4 Gy in daily fractions of 1.8 Gy. Rectal surgery was performed 7–8 weeks after the end of neoadjuvant treatment. Eight courses of adjuvant chemotherapy with FOLFOX4 plus panitumumab at a dose of 6 mg/kg, every 2 weeks, were given after surgery. The primary endpoint of the study was the complete pathological response rate. Results: From February 2007 to December 2008, 35 out of the 55 planned pts were enrolled. Twenty nine pts completed neoadjuvant treatment and 20 underwent surgery (15 pts ongoing). The characteristics of 29 pts were: males 19 (65.5%) and females 10 (34.5%); median age 58 years (range 39–78); median Karnofsky PS 100 (range 70–100); stage: uT3N+ 22 (75.9%), uT4N- 3 (10.3%), uT4N+ 4 (13.8%). The most frequent grade 1–4 side-effects were acneiform rash (96.2%), diarrhea (51.7%) and fatigue (14.3%). Grade 3 diarrhea was registered in 35.7% pts, and grade 3–4 cutaneous toxicity in 51.8%. No grade 3–4 hematological toxicity was found. The median cumulative dose of delivered radiotherapy was 50.4 Gy. The planned dose of panitumumab, 5-fluourouracil and oxaliplatin was administered in 83%, 72% and 67% of pts, respectively. Conclusions: Despite the moderate increase of diarrhea, these early results demonstrate that panitumumab can be safety added to 5-fluorouracil/oxaliplatin-based chemoradiotherapy, without compromising the concurrent radiotherapy dose. No significant financial relationships to disclose.
Long-term antithrombotic therapy and risk of intracranial haemorrhage from cerebral cavernous malformations: a population-based cohort study, systematic review, and meta-analysis
Authors: Susanna M Zuurbier, Charlotte R Hickman, Christos S Tolias, Leon A Rinkel, Rebecca Leyrer, Kelly D Flemming, David Bervini, Giuseppe Lanzino, Robert J Wityk, Hans-Martin Schneble, Ulrich Sure, Rustam Al-Shahi Salman
Journal: The Lancet Neurology (2019)

BackgroundAntithrombotic (anticoagulant or antiplatelet) therapy is withheld from some patients with cerebral cavernous malformations, because of uncertainty around the safety of these drugs in such patients. We aimed to establish whether antithrombotic therapy is associated with an increased risk of intracranial haemorrhage in adults with cerebral cavernous malformations.MethodsIn this population-based, cohort study, we used data from the Scottish Audit of Intracranial Vascular Malformations, which prospectively identified individuals aged 16 years and older living in Scotland who were first diagnosed with a cerebral cavernous malformation during 1999–2003 or 2006–10. We compared the association between use of antithrombotic therapy after first presentation and the occurrence of intracranial haemorrhage or persistent or progressive focal neurological deficit due to the cerebral cavernous malformations during up to 15 years of prospective follow-up with multivariable Cox proportional hazards regression assessed in all individuals identified in the database. We also did a systematic review and meta-analysis, in which we searched Ovid MEDLINE and Embase from database inception to Feb 1, 2019, to identify comparative studies to calculate the intracranial haemorrhage incidence rate ratio according to antithrombotic therapy use. We then generated a pooled estimate using the inverse variance method and a random effects model.FindingsWe assessed 300 of 306 individuals with a cerebral cavernous malformation who were eligible for study. 61 used antithrombotic therapy (ten [16%] of 61 used anticoagulation) for a mean duration of 7·4 years (SD 5·4) during follow-up. Antithrombotic therapy use was associated with a lower risk of subsequent intracranial haemorrhage or focal neurological deficit (one [2%] of 61 vs 29 [12%] of 239, adjusted hazard ratio [HR] 0·12, 95% CI 0·02–0·88; p=0·037). In a meta-analysis of six cohort studies including 1342 patients, antithrombotic therapy use was associated with a lower risk of intracranial haemorrhage (eight [3%] of 253 vs 152 [14%] of 1089; incidence rate ratio 0·25, 95% CI 0·13–0·51; p<0·0001; I2=0%).InterpretationAntithrombotic therapy use is associated with a lower risk of intracranial haemorrhage or focal neurological deficit from cerebral cavernous malformations than avoidance of antithrombotic therapy. These findings provide reassurance about safety for clinical practice and require further investigation in a randomised controlled trial.FundingUK Medical Research Council, Chief Scientist Office of the Scottish Government, The Stroke Association, Cavernoma Alliance UK, and the Remmert Adriaan Laan Foundation.
Incidence of Infections and Second Cancers in Philadelphia Chromosome-Negative Patients with Myeloproliferative Neoplasms Treated with Ruxolitinib
Authors: Ellen K Ritchie, Spencer Krichevsky, Gail J. Roboz, Richard T Silver, Andrew I Schafer, Joseph Scandura, Pinkal Desai, Sangmin Lee, Michael Samuel
Journal: Blood (2017)