tbuckley/cabot-search huggingface dataset:
Prognostic implications of comprehensive imaging with PET-CT, MRI, and X-rays and their biological and molecular correlates in multiple myeloma (MM) treated with total therapy 3 (TT3)
Authors: T. B. Bartel, T. Brown, J. Haessler, J. Shaughnessy, E. Angtuaco, E. Anaissie, F. van Rhee, R. Walker, J. Crowley, B. Barlogie
Journal: Journal of Clinical Oncology (2009)

8532 Background: PET and MRI can reveal intramedullary focal lesions (FL) before osteolysis is detected on metastatic bone survey (MBS). Diagnostic merits, biological/molecular correlates, and outcome implications of the imaging techniques were prospectively and serially evaluated in 269 of 303 newly-diagnosed patients receiving TT3. Methods: Examined were FL number identified by PET (FDG-FL), CT portion of PET (CT-FL), MRI (MRI-FL), and MBS (MBS-FL); additionally, max-SUV of FL (SUV-FL), diffusely-involved bone marrow (SUV-DI), and extramedullary disease (EMD) on PET-CT. Results were compared, laboratory correlates examined (eg: gene expression profiling [GEP]-derived risk, molecular subgroups), and outcome implications determined. Results: Comparing anatomic sites, PET detected the highest mean FL followed by MRI and MBS (p&lt;0.0001). Univariately significant implications on overall and event-free survival (OS, EFS) of FDG-FL, MBS-FL, and EMD may be explained by their link to other prognostic variables. Applying tertile frequency distributions of all imaging parameters, significant associations were seen for B2M with MBS-FL, FDG-FL, SUV-DI; CRP with MRI-FL, FDG-FL, CT-FL; GEP-defined high-risk with MRI-FL, FDG-FL, MBS-FL, SUV-FL; GEP low bone (LB) disease with MRI-FL, FDG-FL, SUV-FL; GEP Proliferation (PR) subgroup with MRI-FL, FDG-FL, MBS-FL, CT-FL. Yet on multivariate analysis, OS was independently adversely affected by both SUV-FL (&gt;11) (p=0.001) and MRI &gt;23 (p=0.043) in addition to cytogenetic abnormalities (CA) (p=0.005), B2M (&gt;5.5mg/L) (p=0.005), and LDH ((ULN) (p=0.017). Even with GEP-defined high-risk (p=0.008), SUV-FL (&gt;11) (p=0.009) retained independent significance in addition to CA (P&lt;0.001) and CRP (&gt;8mg/L) (p=0.020). Conclusions: This first prospective comprehensive imaging approach to MM showed that high SUV-FL had significant survival implications even after adjusting for powerful prognostic variables, especially GEP-defined risk. Multifaceted correlations of imaging variables also with molecular features of MM underscore the key role of bone (“soil”) for MM (“seed”) development and progression. [Table: see text]
Membranous Nephropathy: Quantifying Remission Duration on Outcome
Authors: Daniel C. Cattran, Esther D. Kim, Heather Reich, Michelle Hladunewich, S. Joseph Kim
Journal: Journal of the American Society of Nephrology (2016)

Although change in proteinuria has been proposed as a surrogate for long-term prognosis in membranous nephropathy (MGN), variability in proteinuria levels and lag between these changes and acceptable end points, such as ESRD, has limited its utility. This cohort study examined the prognostic significance of remission duration in 376 patients with biopsy–proven idiopathic/primary MGN who achieved a remission after a period of nephrotic-range proteinuria. We defined complete remission (CR), partial remission (PR), and relapse as proteinuria ≤0.3, 0.4–3.4, and ≥3.5 g/d after CR or PR, respectively. The exposure variable was the remission status of patients at fixed landmarks (3, 6, 12, 24, and 36 months) after the date of first remission. The primary outcome was ESRD or 50% reduction in eGFR. We fitted Cox proportional hazards models to examine the association of remission status at each landmark and the primary end point. Persistent remission associated with unadjusted hazard ratios for the primary outcome that ranged by landmark from 0.35 (95% confidence interval, 0.20 to 0.61) to 0.56 (95% confidence interval, 0.31 to 1.04). Separate analyses for PR and CR yielded similar results. After adjustment, maintaining remission associated with significantly reduced risk of the primary outcome at all landmarks. Durable remissions associated with improved renal survival. Although the longer the remission, the greater the improvement, patients with remission durations as short as 3 months had improved renal prognosis compared with patients who relapsed. This study validates and quantifies PR and CR as surrogates for long-term outcome in MGN.
Abstract B20: Obesity-induced Nlrc4 inflammasome promotes angiogenesis in breast cancer
Authors: Ryan Kolb, Liem Phan, Nicholas Borcherding, Yinghong Liu, Fang Yuan, Ann M. Janowski, Qing Xie, Kathleen R. Markan, Wei Li, Matthew J. Potthoff, Enrique Fuentes-Mattei, Leslie G. Ellies, Michael Knudson, Mong-Hong Lee, Sai-Ching Jim Yeung, Suzanne L. Cassel, Fayyaz S. Sutterwala, Weizhou Zhang
Journal: Cancer Research (2016)

Abstract Obesity, which impacts 36% of adults in the U.S., is associated with an increased risk of ER-positive breast cancer in postmenopausal women, increased incidence of the more aggressive triple negative breast cancer, increased risk of developing invasive ductal carcinoma (IDC) versus ductal carcinoma in situ (DCIS; non-invasive) and a worse clinical outcome. There have been many hypotheses to explain this link between obesity and breast cancer, but a causal mechanism is still largely missing. Here, using two syngeneic orthotopic transplant models in C57Bl/6 mice, we examined the role of obesity-associated inflammasome activation/IL-1 signaling in obesity-driven breast cancer progression. Our results show that the tumor microenvironment under the conditions of obesity promotes Nlrc4 inflammasome activation in tumor-infiltrating myeloid cells, which in turn leads to IL-1β activation which promotes tumor progression. Further studies show that obesity-induced Nlrc4 inflammasome activation/IL-1β promotes increased angiogenesis and upregulation of Vegfa, primarily in adipocytes. Finally, treatment of mice with Metformin inhibited obesity-associated angiogenesis and breast cancer progression. This data provides evidence for obesity-induced Nlrc4 inflammasome mediated activation of IL-1β as a causal mechanism for obesity-driven breast cancer progression and a rationale for blockade of IL-1 signaling, the use of anti-angiogenesis therapies, or treatment with metformin in obese breast cancer patients. Citation Format: Ryan Kolb, Liem Phan, Nicholas Borcherding, Yinghong Liu, Fang Yuan, Ann M. Janowski, Qing Xie, Kathleen R. Markan, Wei Li, Matthew J. Potthoff, Enrique Fuentes-Mattei, Leslie G. Ellies, Michael Knudson, Mong-Hong Lee, Sai-Ching Jim Yeung, Suzanne L. Cassel, Fayyaz S. Sutterwala, Weizhou Zhang. Obesity-induced Nlrc4 inflammasome promotes angiogenesis in breast cancer. [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 B20.
Ultra-Deep Sequencing (UDS) Allows More Sensitive Detection of the D816V and Other Kit Gene Mutations in Systemic Mastocytosis
Authors: Caterina De Benedittis, Simona Soverini, Cristina Papayannidis, Michela Rondoni, Sabrina Colarossi, Francesca Dal Pero, Luca Zazzeroni, Roberta Zanotti, Giovanna De Matteis, Serena Merante, Chiara Elena, Federica Irene Grifoni, Massimiliano Bonifacio, Omar Perbellini, Giorgina Specchia, Livio Pagano, Domenica Gangemi, Patrizia Bonadonna, Lisa Pieri, Michele Cavo, Giovanni Martinelli
Journal: Blood (2014)
Combination immunotherapy with rituximab and local delivery of CpG oligonucleotide in a syngeneic murine model expressing human CD20
Authors: S. A. Hurvitz, D. Betting, K. Kafi-Tehrani, J. Golay, T. Olafsen, A. M. Wu, J. M. Timmerman
Journal: Journal of Clinical Oncology (2006)

2502 Background: Immunostimulatory agents such as CpG oligonucleotides (CpG) may improve the efficacy of rituximab (R) by augmenting antibody-dependent cellular cytotoxicity. We have generated a murine B cell lymphoma expressing human CD20 (38C13-huCD20) for growth in syngeneic wild-type (WT) mice to efficiently study combination immunotherapy in an immunocompetent model. Methods: Groups of mice were inoculated s.c. with tumor cells and after tumor establishment, were treated with R on days 1 and 3, and either intratumoral (i.t.) or systemic (intraperitoneal, i.p.) CpG days 1, 2, 3, 5, 7 and 9. Tumor size was monitored daily and animals sacrificed when tumors reached 1.4 cm. Results: 38C13-huCD20 tumors were shown to express high levels of CD20 by flow cytometry, immunohistochemistry and microPET. While single agent R prevented growth of 100% of tumors when given on the day of inoculation, therapy of established tumors with either R or CpG alone provided no cures. In contrast, R plus i.t. CpG resulted in complete regressions (CR) of tumors in some mice. The route of CpG delivery was critical as only i.t., not systemic (i.p.) CpG combined with R led to CRs. All mice with CR survived challenge with a lethal dose of WT tumor cells, suggesting induction of immunity against non-human CD20 tumor antigens. Cyclophosphamide (Cy) was used to cytoreduce bulky tumors prior to treatment with R/CpG. Cy alone resulted in initial tumor shrinkage but no cures. In this stringent setting, there were no survivors after Cy/R. Long term tumor-free survivors were seen only in mice receiving i.t. CpG ± R. Addition of i.t. CpG significantly improved survival over Cy/R (p=0.018), while addition of i.p. CpG did not (p=0.24). Adding a second cycle of R/CpG i.t. on day 14 after Cy further improved survival (day 55) compared to 2 cycles of R alone (p=0.01) or 2 cycles of i.t. CpG alone (p=0.002). Conclusions: We have identified a novel combination immunotherapy resulting in eradication of an aggressive B cell lymphoma. Admininstration of CpG into the tumor bed was critical in enhancing the R effect. Ongoing studies are evaluating underlying immunologic mechanisms. Such models should allow identification of promising strategies appropriate for translation into clinical trials. [Table: see text]
Beyond conflict of interest
Authors: R. Smith
Journal: BMJ (1998)

Conflict of interest is being taken more seriously by doctors and by society at large. The New England Journal of Medicine has twice recently been heavily criticised for failing to declare authors’ conflicts of interest—despite its declared policy of doing so.1,2 Last week the BBC halted a £360 000, well reviewed television series because of a “potential conflict of interest”: the producer owned commercial property featured in the series.3 Despite the rising concern, medical journals have done an indifferent job in tackling the problem.4 Four years ago I wrote an editorial arguing that we had to do better,5 and we began then to require all authors to sign forms declaring conflicts of interest. Unfortunately authors often fail to declare conflicts of interest. This issue of the BMJ contains a collection of material on the subject, and we are proposing new policies.
A phase II study of anastrazole and fulvestrant in combination with gefitinib in patients with newly diagnosed ER-positive breast cancer
Authors: S. A. Massarweh, Y. L. Tham, H. Weiss, S. Fuqua, J. Huang, R. Elledge
Journal: Journal of Clinical Oncology (2007)

1050 Background: Endocrine therapy for ER+ breast cancer is effective and relatively nontoxic, but is limited by de novo and acquired resistance. Preclinical studies suggest that complete ER blockade along with inhibition of co-expressed growth factor receptors enhances endocrine response and overcomes resistance. Methods: We conducted a phase II trial of combined anastrazole and fulvestrant with gefitinib, an EGFR tyrosine kinase inhibitor, as intial therapy in postmenopausal women with locoregional or metastatic ER+ breast cancer. A tumor core biopsy was done at baseline and after 3 weeks. Patients received treatment for 4 months. Surgery was then offered if the tumor was operable. Primary endpoint was clinical response as defined by RECIST criteria and secondary endpoints were safety/tolerability, complete pathologic response rate (pCR), and biomarker analysis. Planned sample size was 60 patients, but the study closed after 15 patients were enrolled because of poor accrual. Results: Median age at diagnosis was 67 years. Median clinical tumor size was 7 cm and 4 patients had metastases. 11 patients (73%) had ER+/PgR+ tumors and 4 (27%) had ER+/PgR- disease. 3 patients withdraw from the study before response was assessed. Of the12 remaining patients there were 2 complete responses (17%), 5 partial responses (42%), 5 with stable disease (42%), and 2 (17%) with progressive disease. Of the 7 patients who had surgery at 4 months, none had pCR. Most common adverse events were rash in 4 patients, Diarrhea in 4, joint symptoms in 3, and abnormal LFT’s in 3. All adverse events were reversible. Biomarkers, including arrays and Ki67, are pending and will be presented at the meeting. Conclusions: Complete ER blockade using anastrazole and fulvestrant with EGFR inhibition is well-tolerated and has activity in this cohort of patients with relatively advanced ER+ breast cancer. Despite its documented benefit and low toxicity, accrual to neoadjuvant endocrine therapy studies remains poor in the US, largely because of physician hesitance to refer patients for non-chemotherapy studies. More effort is needed to increase physician awareness about the value of endocrine therapy, and to increase accrual to trials that address the question of endocrine resistance. [Table: see text]
Intrapericardial cellular immunotherapy for malignant pericardial effusion using autologous IL-2-activated TILs
Authors: U. Toh, T. Fujii, N. Seki, E. Ogo, K. Shirouzu, H. Yamana
Journal: Journal of Clinical Oncology (2006)

2555 Background: Pericardial effusion (PE) and cardiac tamponade caused by malignant pericarditis are critical conditions in cancer patients, which still lack a recommended protocol for their long-term management. The aims of this study were to investigate the presence of cytotoxic T lymphocytes (CTLs) in malignant PE and to determine the clinical response to administering autologous tumor-infiltrating lymphocytes (TILs) into the pericardial cavity. Methods: Initially, we identified human lymphocyte antigen class-I-restricted and tumor-specific CTLs within the interleukin-2 (IL-2)-activated TILs in PEs from four patients, on the basis of interferon-g production and lactate dehydrogenase-release assays. Clinically we observed favorable responses to the pericardial transfer of IL-2-activated autologous TILs in four patients: one male with advanced esophageal cancer, one female with recurrent lung cancer and two female with recurrent breast cancer, respectively. Autologous TILs from PEs were expanded in vitro with IL-2, characterized for CD3, CD4 and CD8 markers, checked for contamination and then infused into the patient’s pericardial space through a catheter. This was repeated biweekly. Results: After treatment, there were no signs of recurrence of PE in either case, as determined by radiography, echocardiography and computed tomography. The only adverse effects seen were grade 1 fevers. Conclusions: These results suggested that intrapericardial cellular immunotherapy with autologous TILs could be a safe and effective treatment for controlling malignant pericarditis with associated cardiac tamponade, and that tumor-specific CTLs present in malignant PE might be important for tumor rejection. No significant financial relationships to disclose.
GW26-e0687 The Endoplasmic Reticulum Stress Signaling Pathways in Protection of Myocardium Ischemia/Reperfusion Injury Model Rats by Pioglitazone
Authors: Huanzhen Chen, Xiangli Cui, Xiuping Jiang, Yan Li, Wenyan Ma
Journal: Journal of the American College of Cardiology (2015)
Effect of High Levels of Growth Differentiation Factor 15 (GDF15) On Hepcidin Expression in Monocytes of β-Thalassemia Intermedia Patients.
Authors: Kleber Yotsumoto Fertrin, Carolina Lanaro, Carla Fernanda Franco-Penteado, Dulcinéia M Albuquerque, Mariana R. B. Mello, Marcos André C Bezerra, Betania Lucena Borges Tavares Domingues, Sara T.O Saad, Aderson S Araujo, Fernando Ferreira Costa
Journal: Blood (2009)
Evaluation of thymoquinone (TQ) as an antiproliferative, proapoptotic, and immunomodulatory agent in a non-small cell lung cancer cell (NSCLC) line
Authors: S. H. Jafri, J. Glass, R. Shi, H. Kleiner
Journal: Journal of Clinical Oncology (2009)

e14644 Background: NSCLC is the most common cause of cancer death worldwide. We performed in vitro testing of Thymoquinone (TQ), a derivative of black caraway seed against NSCLC cell line NCI-H460 Methods: Cells were grown in RPMI and were plated at a density of 5,000 cells per well in a 96 well plate and cell growth determined in the presence of 80 and 100μM of TQ dissolved in DMSO with appropriate solvent only as control. Cell proliferation was determined at 24, 48 and 72 hrs intervals using 3-(4,5-dimethyltiazol 2-yl)-2,5-diphenyltetraolium bromide (MTT) assay. Factorial analyses of variance (ANOVA) were used to determine the effect of TQ and control with the time. Student-Newman-Keuls test was used to determine statistical significance with P value &lt;0.05 considered significant. Apoptosis was detected using Annexin V-FITC Aptosis Detection Kit analyzing the effects of TQ at 24 hrs after treatment by flow cytometry. The immunomodulatory effects of TQ were tested using RayBio Human Cytokine Antibody Array C series 200. NCI-H460 cells (50,000 cells per well in duplicate 6 well plates) were grown in serum free RPMI media. 24 hrs after treatment with TQ or DMSO media was collected and analyzed for expression of various cytokines. Results: The MTT assay showed that TQ at 80 and 100 μM significantly inhibited cell growth as compared to control and at 24 hrs for example, 100 μM TQ inhibited cell growth by 78%. Apoptosis occurred rapidly after treatment with TQ with 73.5% of cells being positive for expression of Annexin-V as detected by flow cytometry after 24 hrs of exposure to TQ as compared to 2.6% of controls. The cytokine array revealed that TQ significantly decreased expression of ENA-78(Epithelial neutrophil activating peptide), and GRO (Growth related oncogene).ENA-78 is correlated with vascularity and tumor growth in NSCLC tumor, whereas GRO is associated with neoangiogenesis. Conclusions: TQ is shown to be a powerful anti-proliferative, pro-apoptotic and anti- angiogenic agent in a NSCLC cell line. No significant financial relationships to disclose.
Host Plasmacytoid or Conventional Dendritic Cells Alone Are Sufficient To Initiate Graft-Versus-Host Disease.
Authors: Motoko Koyama, Daigo Hashimoto, Kazutoshi Aoyama, Ken-ichi Matsuoka, Kennosuke Karube, Kiyoshi Takeda, Koichi Ohshima, Koichi Akashi, Mitsune Tanimoto, Mine Harada, Takanori Teshima
Journal: Blood (2007)
Dissecting the role of CXCR7 in Cell Trafficking of Endothelial-Cells and Endothelial-Progenitor-Cells in Multiple Myeloma,
Authors: Abdel Kareem Azab, Feda Azab, Phong Quang, Patricia Maiso, Hai T Ngo, Johann Zimmermann, Kalpana Patel, Barbara Romagnoli, Antonio Sacco, Yang Liu, Yong Zhang, Michaela Reagan, Aldo M Roccaro, Irene M. Ghobrial
Journal: Blood (2011)
Epigenetic Silencing of a Novel Candidate Tumor Suppressor “miR” Predicts Poor Prognosis In High-Risk MDS and AML.
Authors: Marianne B. Treppendahl, Xiangning Qiu, Christoffer Hother, Mette K. Andersen, Lars Kjeldsen, Peter Jones, Gangning Liang, Kirsten Gr∅nbæk
Journal: Blood (2010)
Abstract A12: The immune composition of a spontaneous mouse breast cancer
Authors: Pedro Velica, Helene Rundqvist, Milos Gojkovic, Randall S. Johnson
Journal: Cancer Research (2016)

Abstract The MMTV-PyMT mouse strain is a widely used model for the study of breast cancer. In this strain, the mouse mammary tumor virus (MMTV) promoter drives expression of the polyoma middle T (PyMT) oncogene in breast epithelium resulting in widespread transformation of the tissue and formation of progressive tumors that eventually metastasize to the lungs and lymph nodes, closely recapitulating the human disease. It is know that MMTV-PyMT tumors are infiltrated by large numbers of immune cells and the role of some immune populations in cancer progression and metastasis has been described. However a detailed characterization of the myeloid and lymphoid populations infiltrating MMTV-PyMT during tumor progression is yet to be performed. In this study we used comprehensive flow cytometry panels to enumerate and quantify B cells, αβ T cells (CD4 and CD8), γδ T cells, NK T cells, NK cells, neutrophils, monocytes, dendritic cells and macrophages within MMTV-PyMT tumors in different stages of progression. Given that hypoxia is a prominent aspect of breast cancer we extended this characterization to strains with targeted deletion of hypoxia-inducible factor (HIF) 1α and HIF2α in myeloid cells. We found lymphoid cells to be the predominant immune populations within PyMT tumors particularly B cells and αβ T cells (CD4+ and CD8+) but their frequencies did not markedly change with progression or tumor mass. Surprisingly the majority of CD8 T cells expressed the NK cell marker NK1.1 (&amp;gt;80%). In addition we found dendritic cells (CD11chigh, MHC IIhigh) to be the prevalent myeloid population and that the frequency of this population had a strong positive correlation with tumor mass. Myeloid deletion of HIF1a, but not HIF2a, resulted in increased tumor mass and dendritic cell infiltration while other immune population frequencies remained unchanged. Whether dendritic cells directly affect tumor growth and to what extent HIF1α is involved in this process remains to be elucidated. We expect that this immune characterization of PyMT tumors will serve as a reference for future breast cancer immunology studies and possibly assist in the development of new immunotherapies. Citation Format: Pedro Velica, Helene Rundqvist, Milos Gojkovic, Randall S. Johnson. The immune composition of a spontaneous mouse breast cancer. [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 A12.