tbuckley/cabot-search huggingface dataset:
Prognostic factors correlation with androgen receptor (AR) in triple negative breast cancer (TNBC).
Authors: Maximiliano C Kneubil, Alessandra EF Godoy, Guilherme P Coelho, Sargeele Silva, Aldo DJ Pinheiro, Renato Rombaldi, Fabio Pasqualotto, Bruno W Raimann, Jose Mauro Madi, Mariana Alessi, Nathalia Hoffmann, Mariana Koppe, Mariana E Roesch, Janaina Brollo
Journal: Journal of Clinical Oncology (2015)

e12084 Background: Breast cancer is a heterogeneous and complex disease. TNBC is characterized by intrinsic aggressive tumour biology resulting in poor prognosis. AR is one of the newly emerging biomarkers in TNBC and has been proved to play an important role in the genesis and in the development of breast cancer. In the present study, we explored the correlation of AR expression with age, histological subtype, histological grade, Ki-67 and value of Tumor-Infiltrating Lymphocytes (TIL) in TNBC. Methods: We identified consecutive invasive TNBC from a cancer registry in a single institution between January, 2012 and May, 2014. The biopsies were analyzed by immunohistochemistry for AR, Ki-67, TIL and were correlated with age, histological subtype and histological grade. AR positivity was determined with clone AR 441 antibody (DAKO). When AR was positive, the expressiveness was considered weak when H-score < 150 and strong when H-score > 150. The analysis of percentage of TIL was performed on a single full-face HE-stained tumor section and TIL were defined as the percentage of lymphocytes in direct contact with the tumor cells. Results: 34 TNBC have been analyzed to date. The average age was 51.9 years (range 30-82). Of the 34 TNBC samples, 23 cases (67.7%) were AR-negative and 11 cases (32.3%) were AR-positive. Among the positive cases, the expressiveness was weak in 6 cases and strong in 5 cases. Most of the patients (82%) presented poorly differentiated tumors and all patients presented invasive ductal carcinoma. The average expression of Ki-67 was 65% in AR-negative group and 43.6% in AR-positive group, respectively (p < 0.05). Older age was associated with AR expressiveness, the average age in AR strong expressiveness was 70.8 years (p < 0.005) compared to 42.3 years in group with AR weak expressiveness. The AR expressiveness was not associated with histological grade and TIL. The mean of TIL was 38.6% in the AR-positive group and 39.1% in the AR-negative group (p = 0.3). Conclusions: The present analysis showed that AR expressiveness in TNBC was associated with older patients and tumors with lower expression of Ki-67. However, the expressiveness of RA in patients with TNBC was not associated with the percentage of TIL.
Reproducibility of the Penn predictive score of tumor lysis syndrome (PPS-TLS) in acute myelogenous leukemia (AML)
Authors: A. R. Mato, A. N. Miltiades, M. Guo, D. F. Heitjan, M. P. Carroll, A. W. Loren, D. L. Porter, E. A. Stadtmauer, A. E. Perl, S. M. Luger
Journal: Journal of Clinical Oncology (2006)

6577 Background: In a previous retrospective study of 194 patients undergoing AML induction chemotherapy, we described a TLS predictive model entitled the Penn Predictive Score for Tumor Lysis Syndrome (PPS-TLS). TLS incidence was 9.8%. The PPS-TLS is defined as the sum of the scores for pre-induction lactate dehydrogenase (LDH), uric acid (UA), and gender (see table ). The area under the receiver operator characteristic (ROC) curve for this cohort was 89% (SD 4%). Methods: To validate the PPS-TLS, we retrospectively analyzed a second dataset of 166 AML patients undergoing induction chemotherapy from 2003–2006 at our institution. All patients received TLS prophylaxis. TLS was defined as (i) doubling of baseline serum creatinine (Cr) in association with elevated serum phosphate, UA, or potassium or (ii) elevations in 2 of the above electrolytes within 7 days of initiation of therapy. Potential TLS predictive factors were analyzed for statistical significance. Results: In this new dataset, TLS incidence is 9.6%. Significant in univariate analysis are male sex (OR=6.0, CI 1.31–27.15), Cr (OR=13.0, CI 2.88–58.23), UA (OR=48.6, CI 5.78–408.95), and LDH (OR=1.2, CI 1.03–1.48). In multivariate analysis, LDH (OR=1.3, CI 1.04–1.70) and Cr (OR=6.8, CI 1.48–30.89) remain significant. PPS-TLS scores were calculated and tested for their ability to predict TLS in this dataset. The area under the ROC curve for the PPS-TLS in this dataset was 75% (CI 61%-89%), indicating that the probability that a patient with TLS would have a higher PPS-TLS score than one without TLS is 75%. The current result is not statistically significantly different from the area under the ROC curve in the initial dataset (89%). Conclusions: The PPS-TLS is the first TLS predictive model in AML. The reproducibility of this model is supported by this study. A prospective multisite study is being designed to further validate this model. This analysis may lay the groundwork for the first evidence-based guidelines for TLS monitoring and management in AML. [Table: see text] No significant financial relationships to disclose.
GW26-e2197 Ethnic disparities in recommended anthropometric cut-off values to identify the clustering of cardiovascular risk factors effectively in ostensibly healthy Chinese population in Xinjiang
Authors: Jing Tao, Yining Yang, Xiaomei Li, Fen Liu, Bangdang Chen, Zhen-Yan Fu, Yang Xiang, Xiang Xie, Zixiang Yu, You Chen, Xiaocui Chen, Mintao Ga, Yitong Ma
Journal: Journal of the American College of Cardiology (2015)
Abstract C33: Effects of monocyte chemotactic protein-1 deficiency on spontaneous metastasis of Lewis lung carcinoma in mice fed a high-fat diet
Authors: Lin Yan, Sneha Sundaram
Journal: Cancer Research (2016)

Abstract Obesity is a risk factor for cancer. Adipose tissue is considered an endocrine organ that produces pro-inflammatory adipokines, e.g. monocyte chemotactic protein-1 (MCP-1), that may contribute to obesity-related malignant progression. This study investigated effects of MCP-1 deficiency on pulmonary metastasis of Lewis lung carcinoma (LLC) in male C57BL/6 mice using a spontaneous metastasis model. The high-fat diet (45% of energy from fat) significantly increased the number and size (cross-sectional area and volume) of lung metastases compared to the AIN93G control diet (16% of energy from fat). Deficiency of MCP-1 reduced the number of lung metastases by 37% (p &amp;lt; 0.05) in high-fat diet-fed mice; it reduced metastatic cross-sectional area by 46% (p &amp;lt; 0.05) and volume by 69% (p &amp;lt; 0.05) compared to wild-type mice. Adipose and plasma concentrations of MCP-1 were significantly higher in high-fat diet-fed wild-type mice than in their AIN93G-fed counterparts, but they were not detectable in MCP-1 deficient mice regardless of diets. Plasma concentrations of plasminogen activator inhibitor-1 (PAI-1), tumor necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were significantly higher in MCP-1 deficient mice than in wild-type mice. We conclude that adipose-produced MCP-1, at least partly, contributes to high-fat diet-enhanced metastasis and suggest that the overproduction of inflammatory cytokines (PAI-1, TNF-α) and angiogenic factors (VEGF, TIMP-1) in the absence of MCP-1 may support the metastatic development and growth of LLC in MCP-1 deficient mice. Citation Format: Lin Yan, Sneha Sundaram. Effects of monocyte chemotactic protein-1 deficiency on spontaneous metastasis of Lewis lung carcinoma in mice fed a high-fat diet. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr C33.
Phase II randomized placebo-controlled double-blind chemoprevention trial of fruit/vegetable concentrates on intermediate biomarkers in head/neck cancer.
Authors: E. G. Shaw, L. D. Case, J. D. Browne, J. Gilbert, J. Metzner-Sidurski, E. Franzmann, B. Frizzell, C. Schneider, V. Thomas, J. J. Hu
Journal: Journal of Clinical Oncology (2010)

1521 Background: Head/neck cancer (HNC) patients (pts) are at high risk for developing second primary tumors (SPT). Juice-Plus+ is a proprietary whole food based nutritional supplement which includes juice powder concentrates from 17 different fruits, vegetables and grains (www.juiceplus.com). We conducted a chemoprevention trial to evaluate the effect of this intervention on surrogate endpoint biomarkers (SEB) associated with SPTs. Methods: Eligibility criteria - adult HNC pts disease-free for 6 months to 3 years following surgery, radiation therapy, and/or chemotherapy. Pts were randomized to 12 weeks of daily Juice-Plus+ capsules or placebo. Pre- and post-treatment oral cavity mucosal biopsies and blood tests were obtained. The study primary endpoint was % expression of the cell cycle regulatory protein p27 by immunohistochemistry in the oral mucosal specimens, a SEB for development of SPT. Secondary endpoints included cell proliferation measured by Ki-67, DNA damage, T-cell function, and serum carotenoid and antioxidant levels. Results: Between 2004-2009, 134 pts were entered (72 on Arm A, 62 on Arm B). Pt characteristics: median age 59, 85% male, 89% White, 62% stage III-IV. Toxicity was negligible. P27 and Ki-67 data was available in 72-78% of pts. There was no significant difference in mean positive p27 protein staining between Arms A and B from baseline (35% in both Arms) to 12 weeks (36.6% in Arm A vs. 36.2% in Arm B, higher is better, p = 0.94). However, more pts in Arm A had grade 3 p27 staining intensity than in Arm B, 7.6% at baseline (both arms) vs. 8.4% in Arm A and 6.3% in Arm B at 12 weeks (p = 0.13). Furthermore, pts in Arm A had slightly lower proliferation rates: 24.1% at baseline (both arms) vs. 22.5% in Arm A and 26.5% in Arm B at 12 weeks (p = 0.12). Four SPT have occurred in Arm A, 8 in Arm B. Conclusions: The p27, Ki-67, and SPT data suggest that patients in Arm A have more favorable results compared to those on Arm B. The remaining data, still under analysis, will be presented at which time the code for Arms A and B (Juice-Plus+ or placebo) will be broken. This study was supported by NSA, Inc. and NIH/NCI grants 3 U10 CA 81851 and R21 CA 106205. No significant financial relationships to disclose.
Impact of Molecular Markers and Cytogenetic Abnormalities on Long-Term Overall Survival and Disease-Free Survival after Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) for Acute Myeloid Leukemia (AML) patients
Authors: Mauricette Michallet, Mohamad Sobh, Xavier Thomas, Carole Charlot, Fiorenza Barraco, Giovanna Cannas, Franck E Nicolini, Emmanuelle Nicolas-virelizier, Claudiu Plesa, Youcef Chelghoum, Jacques Troncy, jean-Pierre Magaud, Isabelle Tigaud, Sandrine Hayette
Journal: Blood (2008)
Abstract 18721: Diacylglycerol Kinase ? (DGKB) Genotype Predicts Response to Niacin Induced Flushing and Changes in Insulin in the Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides and Impact on Global Health Outcomes (AIM-HIGH) Trial
Authors: Sony Tuteja, Liming Qu, Richard L Dunbar, Mingyao Li, Megan Mucksavage, Stephanie DerOhannessian, Muredach P Reilly, Daniel J Rader
Journal: Circulation (2013)

Niacin has been used for decades as a lipid lowering agent but its use is limited by flushing. Stimulation of a G-protein coupled receptor (GPR109A) on immune cells of the skin by niacin results in generation of prostaglandinD 2 /E 2 and flushing. An evoked phenotype genetic study (termed the GENE study) was undertaken to determine genes associated with flushing and the findings were validated in the AIM-HIGH cohort receiving niacin. The GENE study recruited n=294 healthy volunteers (51% Female, 65% Caucasian (Cau)) to an IR 1 gm niacin challenge. Flushing was assessed by laser Doppler and quantified as the flux index (peak blood flow divided by baseline). In the AIM-HIGH cohort, 2100 Cau and 75 African-Americans (AA) subjects for whom DNA was available were classified as cases and controls based on flushing severity and frequency during the run-in period of the trial. Genotyping was performed on Human Cardio-Metabo BeadChip (Illumina). Insulin was assayed before and after niacin treatment was begun. In the GENE study, two independent loci in DGKB , a downstream mediator of GPCR signaling (lead SNPs Chr7:14349921, p=1 x 10 -6 and chr7:14281125, p=1.8 x10 -5 ) were associated with the flux index. Fasting insulin levels increased after niacin 94 ± 106% (p&lt;0.0001) at 5 hr compared to baseline. The same SNPs were also associated with the change in insulin. Subjects with the minor alleles had the greatest severity of flushing but the smallest change in insulin. DGKB SNPs were associated with flushing in the AIM-HIGH trial (lead SNP Chr7:14594540p=4 x 10 -4 ). Subjects in the genotype group most associated with flushing had the smallest change in insulin, similar to the GENE study. SNPs in DGKB were associated with flushing in AA in both cohorts, but underpowered for significance. Summary: SNPs in DGKB were associated with flushing and change in insulin levels following niacin and may mediate several pharmacological effects of niacin. Variation in DGKB may alter the GPR109A receptor desensitzation and response to flushing. Since GPR109A has also been found to be expressed on murine islet beta cells, variation in DGKB in this tissue type may modulate insulin production. The role of DGKB in additional pharmacological responses to niacin is currently under study.
Phase III Intergroup Study of Lenalidomide Versus Placebo Maintenance Therapy Following Single Autologous Hematopoietic Stem Cell Transplantation (AHSCT) for Multiple Myeloma: CALGB 100104
Authors: Philip L. McCarthy, Kouros Owzar, Kenneth C. Anderson, Craig C. Hofmeister, David Duane Hurd, Hani Hassoun, Sergio Giralt, Edward A. Stadtmauer, Paul G Richardson, Daniel J. Weisdorf, Ravi Vij, Jan S Moreb, Natalie Scott Callander, Koen Van Besien, Teresa Gentile, Luis Isola, Richard T Maziarz, Don A. Gabriel, Asad Bashey, Heather Landau, Thomas Martin, Muzaffar H. Qazilbash, Denise Levitan, Brian McClune, Vera Hars, John Postiglione, Chen Jiang, Elizabeth Bennett, Susan S Barry, Linda Bressler, Michael Kelly, Michele Sexton, Cara Rosenbaum, Hari Parameswaran, Marcelo C Pasquini, Mary M. Horowitz, Thomas C. Shea, Steven M Devine, Charles Linker
Journal: Blood (2010)
Immune memory in nonclinical models after treatment with NKTR-214, an engineered cytokine biased towards expansion of CD8+ T cells in tumor.
Authors: Deborah H. Charych, Werner Rubas, Vidula Dixit, Janet Cetz, Rhoneil Pena, John L. Langowski, Ute Hoch, Murali Addepalli, Stephen K. Doberstein, Jonathan Zalevsky
Journal: Journal of Clinical Oncology (2016)

11545 Background: NKTR-214 is an immune-stimulatory cytokine designed to provide a controlled, sustained, and CD122-biased receptor signal through the heterodimeric IL2 receptor pathway (IL2Rbg) resulting in an intra-tumoral ratio of CD8T/Treg of > 400.[1] NKTR-214 is currently in a Phase 1 clinical trial to assess the MTD in the outpatient setting, pharmacokinetics, pharmacodynamics and evidence of clinical activity. We here describe the kinetics of IL2 receptor pathway activation and formation of tumor-reactive immune memory after administration of NKTR-214 in mice. Methods: Activation of the IL2 receptor pathway was measured by flow cytometry detecting pSTAT5 from peripheral blood of mice dosed with NKTR-214. Murine breast tumor EMT6 was implanted sc in Balb/c mice and grown to ~100mm3 before treatment with 0.8mg/kg NKTR-214 q9dx3, and 100ug murine anti-CTLA4 q4dx5. CD8 or NK requirements for efficacy were assessed by in vivo depletion through serial anti-CD8 or anti-asialo-GM1 antibody injections, respectively. Anti-tumor memory was assessed by rechallenging tumor-free mice with new tumors and by adoptive spleen transfer from tumor-free mice into recipient mice subsequently implanted with tumor. Results: NKTR-214 treatment resulted in low, sustained activation of pSTAT5 signaling in mice. In contrast, dosing of IL2 (aldesleukin) resulted in an immediate and strong pSTAT5 signal that rapidly decayed. Most of mice implanted with EMT6 murine breast tumors were tumor-free after treatment with the combination of NKTR-214 and anti-CTLA4. When rechallenged with new tumors, 100% of animals rejected the new tumor implants. Depletion of CD8T and NK cells abrogated the anti-tumor response. Adoptive spleen transfer from tumor-free mice to recipient mice inhibited or eliminated subsequent tumors in recipients. Conclusions: NKTR-214 harnesses the immunologically potent IL2 pathway to increase CD8/Treg in tumor and improve response. In nonclinical models, sustained biased signaling through the IL2 pathway enabled by NKTR-214 provides a mechanism of producing an immune memory that is resistant to tumor rechallenge and transferrable to untreated recipient mice.
Potentially modifiable factors contributing to outcome from acute respiratory distress syndrome: the LUNG SAFE study
Authors: John G Laffey, Giacomo Bellani, Tài Pham, Eddy Fan, Fabiana Madotto, Ednan K Bajwa, Laurent Brochard, Kevin Clarkson, Andres Esteban, Luciano Gattinoni, Frank van Haren, Leo M Heunks, Kiyoyasu Kurahashi, Jon Henrik Laake, Anders Larsson, Daniel F McAuley, Lia McNamee, Nicolas Nin, Haibo Qiu, Marco Ranieri, Gordon D Rubenfeld, B Taylor Thompson, Hermann Wrigge, Arthur S Slutsky, Antonio Pesenti
Journal: Intensive Care Medicine (2016)
Targeting of PI3K/AKT/mTOR pathway to inhibit T cell activation and prevent graft-versus-host disease development
Authors: Mª Carmen Herrero-Sánchez, Concepción Rodríguez-Serrano, Julia Almeida, Laura San Segundo, Susana Inogés, Ángel Santos-Briz, Jesús García-Briñón, Luis Antonio Corchete, Jesús F. San Miguel, Consuelo del Cañizo, Belén Blanco
Journal: Journal of Hematology & Oncology (2016)

Graft-versus-host disease (GvHD) remains the major obstacle to successful allogeneic hematopoietic stem cell transplantation, despite of the immunosuppressive regimens administered to control T cell alloreactivity. PI3K/AKT/mTOR pathway is crucial in T cell activation and function and, therefore, represents an attractive therapeutic target to prevent GvHD development. Recently, numerous PI3K inhibitors have been developed for cancer therapy. However, few studies have explored their immunosuppressive effect.The effects of a selective PI3K inhibitor (BKM120) and a dual PI3K/mTOR inhibitor (BEZ235) on human T cell proliferation, expression of activation-related molecules, and phosphorylation of PI3K/AKT/mTOR pathway proteins were analyzed. Besides, the ability of BEZ235 to prevent GvHD development in mice was evaluated.Simultaneous inhibition of PI3K and mTOR was efficient at lower concentrations than PI3K specific targeting. Importantly, BEZ235 prevented naïve T cell activation and induced tolerance of alloreactive T cells, while maintaining an adequate response against cytomegalovirus, more efficiently than BKM120. Finally, BEZ235 treatment significantly improved the survival and decreased the GvHD development in mice.These results support the use of PI3K inhibitors to control T cell responses and show the potential utility of the dual PI3K/mTOR inhibitor BEZ235 in GvHD prophylaxis.
GW26-e3880 The Expression of Ubc9 and the Intensity of SERCA2a-SUMOylation Were Reduced in Diet-induced Obese Rats and Partially Restored by Trimetazidine
Authors: Jing Yao, Tian-Chang Li, Xing-Hui Shao, Zheng-Ming Xu, Meng-Yue Yu, Si-Yong Teng, Yong-Jian Wu
Journal: Journal of the American College of Cardiology (2015)
Omalizumab reduces bronchial mucosal IgE and improves lung function in non-atopic asthma
Authors: Prathap Pillai, Yih-Chih Chan, Shih-Ying Wu, Line Ohm-Laursen, Clare Thomas, Stephen R. Durham, Andrew Menzies-Gow, Raj K. Rajakulasingam, Sun Ying, Hannah J. Gould, Chris J. Corrigan
Journal: European Respiratory Journal (2016)

Omalizumab therapy of non-atopic asthmatics reduces bronchial mucosal IgE and inflammation and preserves/improves lung function when disease is destabilised by staged withdrawal of therapy. 18 symptomatic, non-atopic asthmatics were randomised (1:1) to receive omalizumab or identical placebo treatment in addition to existing therapy for 20 weeks. Bronchial biopsies were collected before and after 12–14 weeks of treatment, then the patients destabilised by substantial, supervised reduction of their regular therapy. Primary outcome measures were changes in bronchial mucosal IgE + cells at 12–14 weeks, prior to regular therapy reduction, and changes in lung function (forced expiratory volume in 1 s) after destabilisation at 20 weeks. Quality of life was also monitored. Omalizumab but not placebo therapy significantly reduced median total bronchial mucosal IgE + cells (p&lt;0.01) but did not significantly alter median total mast cells, plasma cells, B lymphocytes, eosinophils and plasmablasts, although the latter were difficult to enumerate, being distributed as disperse clusters. By 20 weeks, lung function declined in the placebo-treated patients but improved in the omalizumab treated patients, with significant differences in absolute (p=0.04) and % predicted forced expiratory volume in 1 s (p=0.015). Omalizumab therapy of non-atopic asthmatics reduces bronchial mucosal IgE + mast cells and improves lung function despite withdrawal of conventional therapy.
Phase I study of nilotinib in patients (pts) from Japan with imatinib-resistant Ph+ chronic myelogenous leukemia (CML) or acute lymphocytic leukemia (ALL)
Authors: A. Tojyo, Y. Miyazaki, N. Usui, Y. Kobyashi, S. Okamoto, K. Oyashiki, M. Nishimura, M. Okada, H. Natori, H. Tanii
Journal: Journal of Clinical Oncology (2007)

17511 Background: Nilotinib is a highly selective Bcr-Abl tyrosine kinase inhibitor designed to be more potent than imatinib. Results from a phase I study in Japanese pts with imatinib-resistant/intolerant Ph+CML/ALL are reported. Methods: Japanese pts with imatinib-resistant/intolerant Ph+CML (5 CP; 2 AP; 2 BC) or ALL (2) were enrolled in an open-label, dose-escalation study evaluating safety, efficacy and pharmacokinetics (PK) of oral nilotinib. A standard three-pt-per-cohort design was used; initial cohorts included 200mg QD, 400mg QD, and 400mg BID. Serum samples were collected on days 1 and 15 of cycle 1 in all 11 pts. Results: Peak serum concentration was achieved at 4 hrs in most pts. Systemic exposure increased with dose. Serum level reached steady-state within 1 week and was stable over time. The accumulation ratio (AUC day15/day1) was 2 to 3. Nilotinib 400mg BID maintained serum levels &gt;/= 30 times higher than the IC50 required to inhibit Bcr-Abl phosphorylation. No pt experienced dose-limiting toxicity. 7/11 pts had Grade 3/4 AEs, only 1 pt had an AE (thrombocytopenia) suspected as being related to nilotinib treatment. No pt had EKG abnormalities. 57% of all pts and 75% of CML CP pts achieved MCyR. 3 pts in the 200mg QD cohort discontinued due to disease progression, all other pts completed the study. PK results are summarized in Table 1 . Conclusions: Nilotinib PK profile in Japanese pts is comparable to that reported for pts outside Japan. Based on these data, the recommended starting dose of nilotinib in Japanese pts with imatinib-resistant/intolerant Ph+ CML/ALL is 400mg BID. [Table: see text] No significant financial relationships to disclose.