tbuckley/cabot-search huggingface dataset:
Circulating Interleukin 6 in Parkinson Disease
Authors: Gustav Nilsonne, Mats Lekander
Journal: JAMA Neurology (2017)

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Downregulation of Deptor By MiR-155 Promotes Cell Survival through Activation of PI3K/AKT and NFkB Signaling in ABC-Type Diffuse Large B-Cell Lymphomas
Authors: Ewa Jablonska, Patryk Gorniak, Weronika Prusisz, Przemyslaw Kiliszek, Maciej Szydlowski, Tomasz Sewastianik, Emilia Bialopiotrowicz, Anna Polak, Monika Prochorec-Sobieszek, Anna Szumera-Cieckiewicz, Krzysztof Warzocha, Przemyslaw Juszczynski
Journal: Blood (2016)
Estrogens and bone metabolism in postmenopausal women with early breast cancer at low risk treated with exemestane: a randomized placebo-controlled study
Authors: J. Geisler, P. E. Lonning, L. E. Krag, L. Ottestad, Y. Bremnes, A. I. Hagen, E. Schlichting, E. S. Ofjord, A. Polli, G. Massimini
Journal: Journal of Clinical Oncology (2004)

531 Background: Estrogens (Es) reduction in menopause increases osteoporosis and fractures risk. Aromatase inhibitors are being introduced for treating postmenopausal early breast cancer (EBC). Exemestane (E, Aromasin®), a steroidal aromatase inactivator, inhibits peripheral aromatase by 98%, markedly reducing Es. We report the effect of E on Es and bone metabolism in postmenopausal EBC patients (pts). Methods: We conducted a randomized, double blind study of E vs. placebo (P) on bone metabolism, endocrinological and metabolic parameters in postmenopausal pT1N0 or T2N0 (with no other risk factors) or ductal carcinoma in situ (DCIS) pts. ER and/or PgR+ve or unknown pts with bone mineral density (BMD) within 2 SD of the mean for 65-year (yr) women, were randomized to E 25 mg or P p.o. daily for 2 yrs, with a 1-yr follow-up. Primary objective was non-inferiority on BMD. Planned sample size was 128 BMD-evaluable pts. Estradiol (E2), estrone (E1), bone alkaline phosphatase (ALP), PINP, osteocalcin (OC), serum CTX (s-CTX), urinary CTX (u-CTX) and NTX (u-NTX) were evaluated at baseline (BS), 6, 12 and 24 months (mos). Results: 147 pts have been enrolled, 73 E and 74 P. Median age: 61 yrs (E) and 60 yrs (P). Median time from menopause: 9.7 yrs E, 8.0 yrs P. ER and/or PgR: +ve 130 pts, unknown 17 (15 with DCIS). E was well tolerated, 70% of pts had drug-related events on E, 73% on P. Nine pts withdrew on E and 3 on P for adverse events. Three withdrew consent on E and 2 on P. The % change from baseline on Es and bone metabolism markers are described in the Table. Conclusions: E induces a marked Es suppression coupled with an increase in bone resorption (CTX, NTX), and even more in bone formation (ALP, PINP, OC). This indicates an increase of bone remodeling, although no major effect is observed on bone mineral density (Lonning ASCO 2004, submitted). Correlation analyses are ongoing. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Italia S.p.A. Pfizer Co. Pfizer Co.
Vascular endothelial growth factor (VEGF-A) serum levels in standard risk ALL pediatric patients (CCG-1962 study)
Authors: I. A. Avramis, E. H. Panosyan, F. Dorey, J. S. Holcenberg, V. I. Avramis
Journal: Journal of Clinical Oncology (2006)

9026 Background: Many molecular pathways including cell-cycle control, angiogenesis &amp; drug resistance mediate tumor growth and survival. Activation of Akt, PI3K and Ras can be induced by the activation of receptor tyrosine kinases, such as the VEGF-R and related growth factor receptors. VEGF-A serum levels &lt;40 and &gt;100 pg/ml have been associated with good and poor prognoses, respectively. The higher the VEGF-A levels the greater the chance of MRD blasts surviving chemotherapy. ALL blasts secrete VEGF-A and express VEGF-R. The hypothesis was that serum VEGF-A levels in SR ALL pediatric patients at entry of Induction (IND) are predictive of Event-Free Survival (EFS). Methods: 117 patients were entered in CCG-1962 study and were randomized into the Native &amp; PEG-ASNase arms. VEGF-A serum levels in Induction were quantified by an ELISA assay. Results: . All patients had a decrease in VEGF-A levels by Day 14 of IND, but they later dichotomized; with EFS group levels remained low and Event group increasing. The VEGF-A levels at the end of IND remained unchanged in all patients in the DI1 and DI2 treatment phases. A linear relationship exists between high VEGF-A levels at entry to IND and time to Event. Moreover, 7 yr EFS patients have lower VEGF-A average levels of 28±2 pg/ml than Event patients, &gt;100 pg/ml (P&lt;0.01). VEGF-A levels were analyzed by STATA-9 to yield Kaplan-Meier curves. Various cut-off values of VEGF-A were used, with the 30 and 60 pg/ml being the most significant. Low VEGF-A levels at entry or at the end of IND had superior EFS (P&lt;0.0001). In addition, these patients were examined for Δ-VEGF-A positive or not positive. These analyses produced a significant difference, in that patients who had an increase in serum levels of VEGF-A from IND to a later treatment phase had an Event and the patients who had a decrease or no change were EFS (P&lt;1E-6). Bifurcation by Native or PEG-ASNase arm did not alter these results. Conclusions: These results taken together with the results from other studies, strongly support that high VEGF-A serum concentrations in IND and no increase in Δ-VEGF-A are treatment-independent surrogate markers for EFS. Since many studies have demonstrated the same fact, an anti-VEGF-A modality may be useful to enhance the outcome of the ALL patients. No significant financial relationships to disclose.
Immuno-Angioprevention by IL-12 gene transfer
Authors: Douglas M. Noonan, Monica Morini, Roberta Venè, Raffaella Dell’eva, Girieca Lorusso, Michele Cilli, Gianfranco Fassina, Massimo Nicolò, Karin Karin Mölling, Bao Lu, Silvano Ferrini, Adriana Albini
Journal: Cancer Research (2004)

53   IL-12 is a Th1 cytokine that harbors anti-angiogenic effects thought to be mediated by an IFN-gamma and angiostatic CXCR3 chemokine ligand cytokine cascade. Naked DNA intra-muscular injection of an expression vector plasmid producing IL-12 resulted in low but significant, well-tolerated elevation of serum IL-12 levels. Injection of the IL-12 plasmid at least 2 days, and up to 20 days, before subcutaneous injection of matrigel with angiogenic factors resulted in strong prevention of angiogenesis in both C57/bl and nude mice. A single injection of the IL-12 plasmid contemporarily with the matrigel or 2 days after resulted in partial, statistically not significant inhibition. Control plasmid injection did not effect either angiogenesis or angiogenesis inhibition by IL-12 protein in vivo. Angiogenesis inhibition was observed in NK cell depleted C57/bl and nude mice as well as in IFN-gamma-/- and CXCR3-/- knock-out mice, indicating NK and/or T-cell initiated IFN-gamma-chemokine cascades were not involved in the angiogenesis inhibition observed in vivo. We then demonstrated that preventive IL-12 plasmid DNA gene transfer significantly reduced the growth and vascularization of highly angiogenic KS-Imm human Kaposi’s sarcoma and TS/A murine mammary carcinoma tumors in nude and/or syngeneic mice. To further study the effects of IL-12 angiogenesis inhibiton on tumor growth, KS-Imm or the murine uveal melanoma cell line 99E1 were transfected with a related pIRES IL-12 expression vector driven by the CMV promoter. G418 resistant clones were selected and the level of IL-12 mRNA expression and protein IL-12 protein release were analyzed, respectively, by RT-PCR and ELISA assays. IL-12 transfected KS-Imm cells were essentially unable to form tumors in nude mice; these animals showed high levels of serum IL-12 and toxicity. Mock-transduced 99E1 cells, which do not produce IL-12 on their own, formed tumors when injected subcutaneously in nude mice. In contrast, 99E1 cells transfected with the IL-12 vector formed small tumors, and showed well tolerated, intermediate levels of serum IL-12. Orthotopic intraoccular injection of the IL-12 transduced 99E1 cells rarely formed tumors as compared to the mock and wild-type controls. These data suggest that a preventive gene therapy approach using anti-angiogenic cytokines can effectively inhibit tumor angiogenesis and KS, representing an example of angio-immune-prevention.
RNA Sequencing of Bone Marrow Derived Mesenchymal Stromal Cells (MSCs) of Healthy Young, Healthy Old and Patients with Myelodysplastic Syndrome (MDS) Reveals Transcriptomic Changes upon Aging of the Niche and Onset of MDS
Authors: Johann-Christoph Jann, Maximilian Mossner, Florian Nolte, Tobias Boch, Verena Nowak, Iris Palme, Julia Obländer, Jovita Pressler, Christina Xanthopoulos, Henning Röhl, Wolf-Karsten Hofmann, Daniel Nowak
Journal: Blood (2016)
PROGNOSTIC ROLE OF VENTRICULAR-ARTERIAL COUPLING IN PATIENTS WITH LEFT VENTRICULAR DYSFUNCTION SUBMITTED TO CARDIAC RESYNCHRONIZATION THERAPY
Authors: Federica De Vecchi, Eleonora Prenna, Enrico Boggio, Miriam Gravellone, Andrea Magnani, Eraldo Occhetta, Paolo Marino
Journal: Journal of the American College of Cardiology (2017)
CHRONIC PERFORMANCE OF COMMUNICATING LEADLESS ANTI-TACHYCARDIA PACEMAKER AND SUBCUTANEOUS IMPLANTABLE CARDIOVERTER DEFIBRILLATOR
Authors: Fleur Tjong, Tom Brouwer, Brendan Koop, Brian Soltis, Allan Shuros, Martin Burke, Reinoud Knops
Journal: Journal of the American College of Cardiology (2017)
Adding Celecoxib With or Without Zoledronic Acid for Hormone-Naïve Prostate Cancer: Long-Term Survival Results From an Adaptive, Multiarm, Multistage, Platform, Randomized Controlled Trial
Authors: Malcolm D. Mason, Noel W. Clarke, Nicholas D. James, David P. Dearnaley, Melissa R. Spears, Alastair W.S. Ritchie, Gerhardt Attard, William Cross, Rob J. Jones, Christopher C. Parker, J. Martin Russell, George N. Thalmann, Francesca Schiavone, Estelle Cassoly, David Matheson, Robin Millman, Cyrill A. Rentsch, Jim Barber, Clare Gilson, Azman Ibrahim, John Logue, Anna Lydon, Ashok D. Nikapota, Joe M. O’Sullivan, Emilio Porfiri, Andrew Protheroe, Narayanan Nair Srihari, David Tsang, John Wagstaff, Jan Wallace, Catherine Walmsley, Mahesh K.B. Parmar, Matthew R. Sydes
Journal: Journal of Clinical Oncology (2017)

Purpose Systemic Therapy for Advanced or Metastatic Prostate Cancer: Evaluation of Drug Efficacy is a randomized controlled trial using a multiarm, multistage, platform design. It recruits men with high-risk, locally advanced or metastatic prostate cancer who were initiating long-term hormone therapy. We report survival data for two celecoxib (Cel)-containing comparisons, which stopped accrual early at interim analysis on the basis of failure-free survival. Patients and Methods Standard of care (SOC) was hormone therapy continuously (metastatic) or for ≥ 2 years (nonmetastatic); prostate (± pelvic node) radiotherapy was encouraged for men without metastases. Cel 400 mg was administered twice a day for 1 year. Zoledronic acid (ZA) 4 mg was administered for six 3-weekly cycles, then 4-weekly for 2 years. Stratified random assignment allocated patients 2:1:1 to SOC (control), SOC + Cel, or SOC + ZA + Cel. The primary outcome measure was all-cause mortality. Results were analyzed with Cox proportional hazards and flexible parametric models adjusted for stratification factors. Results A total of 1,245 men were randomly assigned (Oct 2005 to April 2011). Groups were balanced: median age, 65 years; 61% metastatic, 14% N+/X M0, 25% N0M0; 94% newly diagnosed; median prostate-specific antigen, 66 ng/mL. Median follow-up was 69 months. Grade 3 to 5 adverse events were seen in 36% SOC-only, 33% SOC + Cel, and 32% SOC + ZA + Cel patients. There were 303 control arm deaths (83% prostate cancer), and median survival was 66 months. Compared with SOC, the adjusted hazard ratio was 0.98 (95% CI, 0.80 to 1.20; P = .847; median survival, 70 months) for SOC + Cel and 0.86 (95% CI, 0.70 to 1.05; P =.130; median survival, 76 months) for SOC + ZA + Cel. Preplanned subgroup analyses in men with metastatic disease showed a hazard ratio of 0.78 (95% CI, 0.62 to 0.98; P = .033) for SOC + ZA + Cel. Conclusion These data show no overall evidence of improved survival with Cel. Preplanned subgroup analyses provide hypotheses for future studies.
RELATIONSHIP BETWEEN WHOLE VESSEL QUANTITATIVE PLAQUE CHARACTERISTICS AND NONINVASIVE FRACTIONAL FLOW RESERVE FROM CORONARY COMPUTED TOMOGRAPHY ANGIOGRAPHY
Authors: Mhairi Katrina Doris, Yuka Otaki, Balaji Tamarappoo, Yoav Arnson, Heidi Gransar, Frances Wang, Sean Hayes, John Friedman, Louise Thomson, Piotr Slomka, Damini Dey, Daniel Berman
Journal: Journal of the American College of Cardiology (2017)
A Phase 1 Trial of TRU-016, An Anti-CD37 Small Modular Immunopharmaceutical (SMIPTM) Protein in Relapsed and Refractory CLL: Early Promising Clinical Activity.
Authors: Leslie Andritsos, Richard R Furman, Ian W Flinn, Andres Foreno-Torres, Joseph M. Flynn, Natarajan Muthusamy, Sarwish Rafiq, Scott Stromatt, John C. Byrd
Journal: Blood (2009)
Identification of the molecular signatures in cutaneous squamous cell carcinoma excised from patients with recessive dystrophic epidermolysis bullosa by using integrated genomic techniques.
Authors: X Mao, C Pourreyron, K Purdie, MV Holder, N Baksh, T Wong, Hiva Fassihi, A Volz, IR Hart, C Harwood, CM Proby, L Bruckner-Tuderman, DP Kelsell, John McGrath, IM Leigh, AP South
Journal: British Journal of Dermatology (2007)
IMPACT OF BALLOON PRE-DILATATION ON HEMODYNAMICS AND CLINICAL OUTCOMES AFTER TRANSCATHETER AORTIC VALVE REPLACEMENT WITH THE SELF-EXPANDING COREVALVE PROSTHESIS
Authors: Toby Rogers, Ron Waksman, J. Kevin Harrison, G. Michael Deeb, James Hermiller, Jeffrey Popma, Michael Reardon
Journal: Journal of the American College of Cardiology (2017)
THE RELATIONSHIP BETWEEN THE QUANTITATIVE EXTENT OF MYOCARDIAL FIBROSIS AND BURDEN OF NON-SUSTAINED VENTRICULAR TACHYCARDIA IN HYPERTROPHIC CARDIOMYOPATHY: A DELAYED CONTRAST ENHANCED MRI STUDY
Authors: Adaya Weissler-Snir, Waseem Hindieh, Danna Spears, Arnon Adler, Dana Fourey, Harry Rakowski, Raymond H. Chan
Journal: Journal of the American College of Cardiology (2017)
Outcomes of patients with triple-negative breast cancer compared to non-triple negative breast cancer: A single-center study.
Authors: Caroline M. Hamm, Maher El-Masri, Rasna Gupta, Swati Kulkarni, Akmal Ghafoor, Pamathy Vivek, John Mathews, Yasmin Alam, Tarek A. Elfiki, Sindu Mary Kanjeekal, Ken Schneider, Ming Pan, Khalid Hirmiz, Colvin Springer, Junaid Yousuf
Journal: Journal of Clinical Oncology (2014)

1123 Background: Triple negative breast cancer is defined as estrogen receptor negative, progesterone receptor negative, Her-2-neu negative breast cancer. The lack of targeted therapies for this patient group has been considered to be a negative prognostic factor. Methods: Twelve hundred thirty four non-triple negative (n-TNBC) breast cancer patients and 167 triple negative (TNBC) patients were reviewed retrospectively. All patients were treated in a single centre in Ontario, and all received standard of care in Ontario, Canada. Hormone receptor positive patients received anti-estrogen therapy, and Her-2 positive patients received chemotherapy and trastuzumab. Results: Although overall progression free survival was statistically inferior for the TNBC group ( p < 0.001), important information is found when analyzed by stage at presentation. Median progression free survival (PFS) was not reached for any stage I, nor stage II patient group. There was no difference in overall survival for stage one between the n-TNBC and the TNBC groups, but was inferior for the TNBC group for Stage II and III. Few relapses were seen in the stage 1 TNBC group, and none were identified after 40 months (median follow-up 40 months). All analyses are as of yet unadjusted. Conclusions: Although the overall outcome of TNBC patients is inferior to their n-TNBC counterparts, their presenting stage is still vitally important in predicting outcome. Stage 1 TNBC carries a good prognosis, possibly better than the NTN counterpart. Ongoing research to identify these TNBC patients at an earlier stage is vital to improving outcomes in this patient population. Variable N (%) OS in years PFS in years Mean Median Log Rank p Mean Median Log Rank P n-TNBC across stages 284 <0.001 130 <0.001 Stage 1 511 (41) 8.4 --- 7.7 --- Stage 2 508 (41) 7.3 9.0 7.1 --- Stage 3 164 (13) 5.9 6.0 5.1 7.0 Stage 4 51 (4) 2.7 2.0 n.r. --- Overall n-TNBC 1234 (100) 7.3 9.0 7.1 TNBC across stages 31.6 <0.001 17.7 0.001 Stage 1 40 (24) 7.7 --- 7.3 --- Stage 2 92 (55) 6.0 --- 6.3 --- Stage 3 33 (20) 4.3 5.0 4.0 --- Stage 4 2 (1) 1.0 0.0 1.0 1.0 Overall TNBC 167 (100) 6.1 --- 6.2 --- n-TNBC versus TNBC 314 < 0.001 145 < 0.001
Pre-Transplant Risk-Assessment for Patients with Acute Myeloid Leukemia (AML) Receiving Allogeneic Hematopoietic Stem Cell Transplants.
Authors: Philipp G. Hemmati, Theis H. Terwey, Philipp le Coutre, Gero Massenkeil, Lam G Vuong, Christian Jakob, Arturo Vega, Bernd Dörken, Renate Arnold
Journal: Blood (2009)
MICROVASCULAR BLOOD FLOW ABNORMALITIES IN PATIENTS WITH PERIPHERAL VASCULAR DISEASE AND ABNORMAL VERSUS NORMAL ANKLE BRACHIAL INDICES
Authors: Thomas Richard Porter, Feng Xie, George P. Casale, Hernan Hernandez, Constance Mietus, Holly DeSpeigelaere, Iraklis Pipinos
Journal: Journal of the American College of Cardiology (2017)
Prevalence of incidental actionable germline mutations in 1,000 advanced cancer patients on a prospective somatic genomic profiling program.
Authors: Funda Meric-Bernstam, Lauren Brusco, Molly S Daniels, Louise C. Strong, Kenna Rael Shaw, Karen H. Lu, Yuan Qi, Humberto Lara-Guerra, Jennifer Keating Litton, Hao Zhao, Agda Karina Eterovic, Banu Arun, Mark Routbort, Filip Janku, Michael A. Davies, Scott Kopetz, John Mendelsohn, Gordon B. Mills, Ken Chen
Journal: Journal of Clinical Oncology (2015)

1510 Background: Next generation sequencing is increasingly used in cancer research and precision oncology. This practice may also reveal germline variants of potential clinical significance. We here report patient preferences for return of results as well as the prevalence of incidental deleterious germline mutations. Methods: Targeted exome sequencing of 202 genes was performed on tumor and normal DNA in a research laboratory. This panel included 18 genes for which return of incidental deleterious findings is recommended by The American College of Medical Genetics and Genomics. Mutations in these genes, as well as PALB2, were considered actionable. Results were confirmed with an orthogonal CLIA assay. A companion protocol determined patient preferences of return of incidental germline results. Return of results was initiated with genetic counseling and repeat CLIA testing. Results: Of 1,000 advanced cancer patients who underwent sequencing, 999 had at least one germline variant in one of the 19 "actionable" genes and 43 had likely pathogenic mutations: BRCA1 (11), BRCA2 (10), TP53 (10), MSH6 (4), PALB2 (2), PTEN (2), TSC2 (1), and RB1 (1). Only 20 (49%) of 43 mutations were known based on clinical genetic testing. The ratio of somatic to pathogenic germline mutations differed by gene; for TP53, 375 patients had somatic mutations and 10 had pathogenic germline TP53 mutations (38 to 1); for BRCA1/2, 106 patients had somatic mutations and 21 had pathogenic germline mutations (5 to 1). The 22 previously unrecognized mutations identified in the research environment were re-tested with an orthogonal CLIA platform with 100% concordance of mutation and interpretation. Of 1,167 patients who consented for a germline testing protocol, 1,157 (99%) stated they would like to be informed of incidental germline results. Initial experience with return of results will be presented. Conclusions: Most patients undergoing genomic testing are comfortable with germline testing and desire return of incidental results. A significant number may have unknown pathogenic mutations. Thus, genomic testing must be accompanied by a plan for return of germline results, in partnership with genetic counseling.
Phase I/II trial of partial breast irradiation (PBI) with various concurrent chemotherapy regimens.
Authors: Lana Maria De Souza Lawrence, Amit Shah, Mary Elizabeth Young, Vered Stearns, Fariba Asrari, Deborah Anne Frassica, Theodore N. Tsangaris, John H. Fetting, Julie R. Lange, Lisa K. Jacobs, Lee Myers, Antonio C. Wolff, Richard C. Zellars
Journal: Journal of Clinical Oncology (2012)

1128 Background: Potential benefits of concurrent chemo-radiation include: shorter duration of treatment, smaller interval between surgery and adjuvant therapies, and synergistic effects. We have previously shown that PBI with concurrent dose dense doxorubicin and cyclophosphamide (ddAC) is well tolerated (Zellars JCO 2009). We performed a follow-up feasibility trial of PBI delivered concurrently with other various chemotherapy regimens. Methods: Women with T1-2, N0-1 breast cancer s/p lumpectomy with ≥2 mm margins were eligible. Chemotherapy regimen was at the discretion of the medical oncologist (Table). PBI (40.5 Gy in 15 daily 2.7 Gy fractions) was delivered within the first 2 cycles of chemotherapy. Primary endpoints were hematologic and non-hematologic toxicities graded according to Common Terminology Criteria for Adverse Events manual (v. 3.0). Results: Thirty-four patients enrolled with median f/u of 19.2 mos. (4.0 - 38.6). Mean tumor size was 1.8 cm (+/- 0.7 cm), 71% pN0, 68% HR +, 18% Her2 +. All patients completed concurrent chemo-radiation. Three patients had a 3-8 day delay in chemotherapy (1 grade 2 thrombocytopenia; 1 Grade 2 liver enzymes; 1 T desensitization). There was 1 local (DCIS) and no regional/distant recurrences or deaths. Toxicity: 2 grade 4 neutropenia (ddAC, TCarboH); 1 grade 3 neutropenia (post-AC paclitaxel); 1 Grade 3 hyponatremia and DVT (TC); 1 syncope (TAC). None had &gt; grade 2 radiation dermatitis. Conclusions: PBI and concurrent chemotherapy is associated with minimal toxicity and appears to be well tolerated. These results deserve further investigation. Funded by The Breast Cancer Research Foundation. [Table: see text]