tbuckley/cabot-search huggingface dataset:
Abstract 5010: A versatile tool to study immune checkpoint therapeutics: Syngenic tumor mouse models in vivo
Authors: Cynthia Schaefer-Obodozie, Peter Jantscheff, Sandra Moor, Steffen Hoffmann, Tihomir Saso, Christoph Schaechtele, Holger Weber
Journal: Cancer Research (2015)

Abstract Checkpoint inhibitor treatment is a common therapy of various cancer types, however, clinical data indicate that patients only partially respond to this regiment due to attenuated anti-tumor immune response. Thus, it has been recognized as important to consider the immune response already during preclinical drug development in animal experiments to anticipate such clinical drawbacks. Although immune-humanized models using human leukocytes in immuno-compromised mice may provide a starting point, syngenic mice models appear to be the better method of choice, reflecting the whole spectrum of a functional immune system. Here, we report on the establishment of syngenic mouse models for breast, colon, kidney and skin cancer both for subcutaneous and orthotopic implantation. Analyzing untreated as well as checkpoint inhibitor treated mice, we will present data on tumor growth kinetics as well on the distribution of immune cells such as Treg cells, M1/M2 macrophages and M/PMN-MDSCs in tumor and spleen tissue based on multi-color flow-cytometric analysis. These data may help to select a suitable model for testing new drug candidates and define a sensitive combination therapy to support the anti-tumor immune defense in addition to checkpoint inhibitor treatment. Citation Format: Cynthia Schaefer-Obodozie, Peter Jantscheff, Sandra Moor, Steffen Hoffmann, Tihomir Saso, Christoph Schaechtele, Holger Weber. A versatile tool to study immune checkpoint therapeutics: Syngenic tumor mouse models in vivo. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5010. doi:10.1158/1538-7445.AM2015-5010
Prevalence and Clinical Correlates of JAK2 Mutations in Pediatric Down Syndrome Acute Lymphoblastic Leukemia.
Authors: Amos S. Gaikwad, Cassia L. Rye, Meenakshi Devidas, Shai Izraeli, Sharon E. Plon, Giuseppe Basso, Andrea Pession, Karen R. Rabin
Journal: Blood (2008)
Hematologic Manifestations and Changes of Cytokines or Hematopoietic Growth Factors in Mice with Iron Overlaod.
Authors: Dae-Chul Jeong, Hui Seung Hwang, Nack Gyun Chung, Bin Cho, Hyun Jung Shin, Hack Ki Kim, Yoo Jin Kim, Chi Wha Han
Journal: Blood (2009)
Induction of the NKG2D Ligands Expression by Histone Deacetylase Inhibitor and Its Impact on the Susceptibility of Leukemic Cells to the Cytolytic Activity of NKG2D-Expressing Cells.
Authors: Naoko Kato, Junji Tanaka, Junichi Sugita, Tomomi Toubai, Yoko Miura, Makoto Ibata, Yusuke Shono, Shuichi Ota, Takeshi Kondo, Masahiro Asaka, Masahiro Imamura
Journal: Blood (2006)
Detection of incidental colorectal malignancies using FDG PET-CT.
Authors: M. Fleming
Journal: Journal of Clinical Oncology (2011)

e14124 Background: Computed tomography (CT) combined with positron emmission tomography (PET) now forms the basis of radiologic diagnosis and staging of many forms of malignancy. Colorectal cancer is the second leading cause of cancer-related death in the western world. Just under 2,000 Irish people are diagnosed and 900 die of colorectal cancer in the Republic of Ireland every year. FDG-PET is a sensitive technology which may detect other abnormalities with staging. Methods: A retrospective study of all fluorine deoxyglucose (FDG) PET-CT scans performed in our institution between January and August 2009 was undertaken (n=629). The radiologic reports were analysed and all scans with focal colonic FDG uptake (n=38) were audited. Colonoscopic and histologic records of those patients who underwent biopsy of suspicious colorectal lesions (n=20) were reviewed. Results: From a total of 629 scans performed, 38 (6%) showed focal FDG accumulation within the colon. 20 of these (52.6%) were felt to warrant further investigation. 14 (36.8%) of those who underwent colonoscopy/sigmoidoscopy had biopies which were positive for dysplasia. 8 (57.1%) biopsies were postive for adenocarcinoma and the remaining 6 (42.8%) biopsies were positive for benign tubular, villous or mixed-type adenomas. One biopsy revealed hyperplasia and 5 showed normal histologic findings. Four out of eight patients (50%) with incidentally-diagnosed colorectal carcinomas had TNM stage I or II disease and underwent curative surgical resection. Histologic results revealed cancerous or precancerous lesions in 14 of the 38 patients (36.8%) with abnormal PET/CT. This equates to a 2.2% overall positive rate for the 629 scans performed in our institution to date. This was higher than expected when compared with similar studies, which have shown a 0.6-1.2% detection rate for colonic lesions. Of those who did undergo endoscopy, 70% were positive for either premalignant adenomas or adenocarcinomas. This implies that colonoscopy is a justified next step in the diagnostic evaluation of patients who display focal FDG uptake in the colon. Conclusions: We found a 2.2% (14/629) rate of incidentally-diagnosed colorectal malignancies, higher than described in the literature.
Allogeneic Stem Cell Transplantation (AlloSCT) for the Treatment of Therapy-Related Myelodysplastic Syndrome (tMDS) and Acute Myeloid Leukemia (tAML): Results from the Center for International Blood and Marrow Transplant Research (CIBMTR).
Authors: Mark Litzow, Waleska S. Pérez, Sergey Tarima, Armand Keating, Jorge Sierra, Martin Tallman, Daniel Weisdorf
Journal: Blood (2007)
Risk stratification in myeloma by detection of circulating plasma cells prior to autologous stem cell transplantation in the novel agent era
Authors: R Chakraborty, E Muchtar, S K Kumar, D Jevremovic, F K Buadi, D Dingli, A Dispenzieri, S R Hayman, W J Hogan, P Kapoor, M Q Lacy, N Leung, M A Gertz
Journal: Blood Cancer Journal (2016)

The impact of circulating plasma cells (CPCs) prior to autologous stem cell transplantation (ASCT) for multiple myeloma has not been defined in the novel agent era. We evaluated the impact of pre-transplant CPCs, detected by six-color flow cytometry in patients undergoing early ASCT on post-transplant response, progression-free survival (PFS) and overall survival (OS). CPCs were detected in 162 out of 840 (19.3%) patients, with the median number of CPCs being 58 per 150 000 events. Ninety-nine percent of patients had received proteasome inhibitor and/or immunomodulator-based induction. The incidence of post-transplant stringent complete response (sCR) in the subgroups with and without CPCs was 15% and 38%, respectively, (P<0.001). The median PFS in the subgroups with and without CPCs was 15.1 (95% confidence interval (CI), 12.5-17.8) and 29.6 months (95% CI, 26.2-32.8), respectively, and the median OS was 41.0 months (95% CI, 32.6-58.2) and not reached (NR) (95% CI, 99.1-NR), respectively, (P<0.001 for both). On multivariate analysis for OS, factors independently predictive of mortality were the presence of CPCs (hazard ratio (HR) 2.5; 95% CI, 1.8-3.6; P<0.001) and sCR post transplant (HR 0.4; 95% CI, 0.2-0.6; P<0.001). Presence of CPCs prior to transplant has a high prognostic impact and should be prospectively validated in clinical trials.
98. Evaluation of Proteasome Inhibitors on AAV-Mediated Transduction Efficiency in Retinal Bipolar Cells
Authors: Shengjie Cui, Qi Lu, Tushar Ganjawala, Gary Abrams, Zhuo-Hua Pan
Journal: Molecular Therapy (2016)

Purpose: Recombinant adeno-associated virus (rAAV) vectors have been a powerful gene delivery vehicle to the retina for basic research and gene therapy. For many of these applications, achieving cell-type specific targeting and high transduction efficiency is desired. Recently, there has been increasing interest in targeted gene expression in retinal bipolar cells, especially for optogenetic gene therapy for vision restoration. However, rAAV-mediated transduction efficiency in retinal bipolar cells is relatively low. The transduction efficiency could be affected by a number of factors, one of which is the proteasome-dependent virus degradation. In this study, we are examining the effect of proteasome inhibitors on the transduction efficiency of rAAV vectors in retinal bipolar cells. Methods: The expression of the transgene, mCherry, was used to evaluate the AAV transduction efficiency. Targeted expression of mCherry in retinal bipolar cells was achieved by rAAV2 vectors carrying an mGluR6 promoter. rAAV vectors at the concentration of 5 × 1012 vg/ml with or without containing proteasome inhibitors were intravitreally injected into the eyes of C57BL/6J mice at about one month of age. Animals were euthanized about one month after virus injection for assessing the expression of mCherry. Results: We tested the effects of three proteasome inhibitors, MG132, doxorubicin, and aclarubicin, on rAAV-mediated transduction efficiency in retinal bipolar cells. Retinas treated with doxorubicin from 200 µM to 800 µM exhibited a concentration-dependent increase in the transduction efficiency. Doxorubicin at the concentration of 2000 µM produced cytotoxicity as evidenced by the thinning of the retinas and decreased the number of mCherry-expressing bipolar cells. The optimal concentration of doxorubicin to enhance the AAV transduction efficiency was 500 µM. MG132 (100 µM, 200 µM, 500 µM) and aclarubicin (50 µM, 100 µM) were not found to enhance the transduction efficiency. Conclusions: Doxorubicin, a proteasome inhibitor, is effective in enhancing rAAV transduction in retinal bipolar cells in mice. Investigation of the mechanism of doxorubicin action may help to further improve the rAAV transduction efficiency in retinal bipolar cells in particular and rAAV-mediated gene delivery in general.
Genetic Alterations of Gα13 Signaling Pathway with BCL2 over-Expression Confers Lymphoma Dissemination and Inferior Outcome in Germinal Center B Cell Diffuse Large B Cell Lymphoma
Authors: Daisuke Ennishi, Anja Mottok, Hennady Shulha, Pedro Farinha, Fong Chun Chan, Barbara Meissner, Merrill Boyle, Susana Ben-Neriah, Christoffer E Hother, Robert Kridel, Ryan Morin, Marco A Marra, Kerry J. Savage, Laurie H. Sehn, Joseph M. Connors, Christian Steidl, David W Scott, Randy D. Gascoyne
Journal: Blood (2015)
PWE-059 A study of patients with cirrhosis admitted to non-transplant general intensive care: prevalence, case mix, outcomes and evaluation of critical illness and disease specific scoring systems
Authors: S J Thomson, C Moran, M L Cowan, S Musa, R Beale, D Treacher, M Hamilton, M Grounds, T M Rahman
Journal: Gut (2010)

<h3>Introduction</h3> Hospital admission rates attributable to cirrhosis are increasing in the UK. The evidence base for the outcome of critically ill patients with cirrhosis admitted to intensive care (ICU) is currently limited to data from tertiary transplant centres that report mortality rates of between 45 and 74%. We hypothesised that the disease cohort experienced in secondary care is less severe than that reported in the literature and would subsequently demonstrate lower mortality. We report the prevalence, case mix and outcomes of a dual centre ICU study in London. <h3>Methods</h3> Data were collected prospectively from two large non-transplant general ICUs in London (St George9s and St Thomas9 Hospitals) over 20 months (November 07–June 09). All ICU admissions were screened for cirrhosis. Clinical data were recorded to calculate and evaluate the performance of several critical illness and disease specific scoring systems (APACHE II, SAPS II, SOFA, Child Pugh, MELD, UKELD, Glasgow Alcoholic Hepatitis Score and the Royal Free Hospital (RFH) score). Study endpoints were ICU and Hospital mortality. <h3>Results</h3> Cirrhosis accounted for 3.3% (137/4198) of ICU admissions. In 118 patients meeting inclusion criteria ICU and hospital mortality rates were 38% and 47%, respectively. Median (IQR) age was 50 (43–59) years, 68% were male, median length of ICU stay was 4.5 (2–10) days and 72% had alcoholic cirrhosis. Median Child Pugh score at presentation was 10 (8–11) (45% Grade A/B), MELD 18 (12–24) and APACHE II 16 (13–22). Hospital mortality was 24% in Child Pugh grade B and 66% in grade C. After multivariate analysis the factors independently predictive of mortality were bilirubin, INR, urea, bicarbonate and pO<sub>2</sub>/FiO<sub>2</sub> ratio. AUROC for the scoring systems ranged from 0.76 (UKELD) to 0.81 (RFH) for the prediction of mortality outcome. Renal failure (OR 3.4 (1.4–8.4)) and renal replacement therapy during admission (OR 9.6 (3.7–24.8)) had strong associations with mortality. Intubation for gastrointestinal bleeding OR 0.4 (0.1–1.3) was associated with a trend towards better outcome than intubation for respiratory failure OR 2.7 (1.0–7.0). <h3>Conclusion</h3> The mortality rates and disease stage reported here are lower than those described in the established literature. Data from specialist transplant centres should not be applied to the patient cohorts seen in general ICUs. We urge critical care physicians to carefully consider the individual clinical case when deciding on ICU admission and not apply potentially misrepresentative figures from previous data sets.
Outcomes and Treatment Patterns of Patients with CML in an Inner-City, Underserved, Multi-Ethnic Patient Cohort Reveals Good Overall Survival with Both First and Second Generation TKIs As Initial Therapy
Authors: Amer Assal, Ramadevi Medavarapu, Ellen W Friedman, Yiting Yu, Amit Verma, Olga Derman
Journal: Blood (2014)
Abnormal joint and bone wound healing in hemophilia mice is improved by extending factor IX activity after hemarthrosis
Authors: Junjiang Sun, Baolai Hua, Eric W. Livingston, Sarah Taves, Peter B. Johansen, Maureane Hoffman, Mirella Ezban, Dougald M. Monroe, Ted A. Bateman, Paul E. Monahan
Journal: Blood (2016)
Normalization of Tumor Vessels by Tie2 Activation and Ang2 Inhibition Enhances Drug Delivery and Produces a Favorable Tumor Microenvironment
Authors: Jin-Sung Park, Il-Kug Kim, Sangyeul Han, Intae Park, Chan Kim, Jeomil Bae, Seung Ja Oh, Seungjoo Lee, Jeong Hoon Kim, Dong-Cheol Woo, Yulong He, Hellmut G. Augustin, Injune Kim, Doheon Lee, Gou Young Koh
Journal: Cancer Cell (2016)
Netlines
Authors: M. Pallen
Journal: BMJ (1997)

# Netlines: The medical establishment on the web {#article-title-2} Note: The BMJ can't guarantee the currency or continued maintenance of URLs or web sites (aside from its own) that appear in Netlines. If a link to a third-party site fails, please consult your favorite search engine. If a BMJ link fails, please send us feedback
Abstract 4262: PRAME as a biomarker for a new molecular subclass of uveal melanoma
Authors: Matthew G. Field, Christina L. Decatur, J. William Harbour
Journal: Cancer Research (2015)

Abstract Introduction: Uveal melanoma is the most common primary intraocular tumor of the eye and has a propensity for fatal hematogenous metastasis. Gene expression profiling is routinely used in clinic to classify uveal melanoma into prognostic subgroups: Class 1 (low metastatic risk) and Class 2 (high metastatic risk). Approximately 40% of Class 2 patients metastasize, which accounts for 85% of metastasis. The remaining 15% of patients that metastasize are Class 1 based on gene expression profiling, however this study demonstrates that the Class 1 patients that metastasize (Class1met+) can be defined as a new molecular subclass, distinct from Class 1 patients that do not metastasize (Class1met-) and Class 2 patients. Methods: Tumor samples from Class1met+ and Class1met- patients with at least 1 year of follow-up underwent histopathologic, cytogenetic and transcriptomic analyses. Results: In a comparison of Class1met+ and Class1met- tumors, the only significant difference was a larger mean basal tumor diameter in Class1met+ tumors. Cytogenetic analyses revealed more extensive copy number gains and losses in Class1met+ tumors. The most significant differentiating features in Class1met+ tumors included 1q gain, 6p gain, 6q loss, and 8q gain. Using principal component analysis, the Class1met+ tumors clustered separately from the Class1met- tumors, indicating the existence of significant transcriptomic differences between the two subgroups. Strikingly, the most highly differentially expressed gene in Class1met+ tumors was preferentially expressed antigen in melanoma (PRAME); mean mRNA expression of PRAME in Class1met+ tumors was 61-fold higher than in Class1met- tumors. Discussion: We define a new subtype of uveal melanoma and demonstrate that gene expression of PRAME can distinguish between Class1met+ patients and Class1met- patients. Citation Format: Matthew G. Field, Christina L. Decatur, J. William Harbour. PRAME as a biomarker for a new molecular subclass of uveal melanoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4262. doi:10.1158/1538-7445.AM2015-4262
Abstract 1769: Rottlerin induces ER stress-mediated cell death in pancreatic stellate cells
Authors: Hsin-Yuan Su, Richard Waldron, Raymond Gong, Stephen Pandol, Aurelia Lugea
Journal: Cancer Research (2015)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease with a 5-year survival rate under 5%. Whereas activated pancreatic stellate cells (PaSC) are important players in PDAC stroma, simultaneously targeting both cancer and stromal cells can be beneficial for cancer therapy. We previously reported that the phytochemical rottlerin dose-dependently reduces PaSC viability through dysregulation of autophagy and induction of apoptosis, and attenuates tumor progression in PDAC experimental models. Interestingly, both rottlerin and metformin have been shown to affect mitochondrial function, and metformin has been demonstrated to induce AMPK-dependent, CHOP-mediated cell death. Here we further studied the mechanisms underlying cell death and autophagy in rottlerin-treated mouse PaSC. Rottlerin rapidly depolarized mitochondrial membrane, increased oxygen consumption and decreased cellular ATP levels and the expression of the mitochondrial transmembrane protein TOM20, suggesting mitochondrial damage. Rottlerin dysregulated autophagy as indicated by rapid and prolonged increasing in LC3I-LC3II conversion and p62/SQSTM1 accumulation. However, rottlerin-induced LC3II did not further change in the presence of inhibitors of autophagic flux, suggesting that rottlerin blocks autophagy progression in PaSC. In addition, rottlerin induced marked AMPK activation and inhibited mTOR signaling. In contrast to metformin, AMPKα1/2 knockdown had no effect on rottlerin-induced inhibition of mTOR signaling and cell viability. Furthermore, rottlerin induced ER stress as manifested by persistent activation of the PERK pathway and upregulation of proapoptotic transcription factor CHOP. Importantly, rottlerin-induced apoptosis was greatly reduced in PaSC isolated from CHOP null mice. In summary, these data indicate that rottlerin reduces PaSC viability through impairing mitochondrial function, inhibiting mTOR signaling and inducing prolonged ER stress. Specifically, CHOP induction plays an important role in determining cell-fate in mitochondria-targeting agents, such as rottlerin and metformin. Citation Format: Hsin-Yuan Su, Richard Waldron, Raymond Gong, Stephen Pandol, Aurelia Lugea. Rottlerin induces ER stress-mediated cell death in pancreatic stellate cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1769. doi:10.1158/1538-7445.AM2015-1769
Complete Loss or Severely Compromised Expression of the Pro-Apoptotic Protein Bax Leads to Resistance to Curcumin-Induced Apoptosis in Burkitt’s Lymphoma Cells.
Authors: Azhar R. Hussain, Maha Al-Rasheed, Pulicat S. Manogaran, Khawla S. Al-Kuraya, Shahab Uddin
Journal: Blood (2005)
Abstract 1562: Proteomic changes observed in colon cancer tumors by label-free differential profiling of paired tumor versus normal FFPE samples
Authors: Lokesh Agrawal, Fiona McAlister, Sushmita Roy, Florian Unger, Kerstin David, Harmut Juhl, Daniel Chelsky, Helen Moore
Journal: Cancer Research (2015)

Abstract Colorectal cancer (CRC) is the third most common cancer and if caught early enough has a good prognosis. Mass screening of the adult population is advisable to reduce CRC mortality rate as well as reduce the cost of treating advanced CRC cases. A blood-based biomarker panel with the ability to diagnose CRC as well as determine prognosis and predict the response to drug therapy is desired. However, blood biomarker discovery is hampered by problems of complexity and dynamic range of protein abundance. Formalin-fixed and paraffin-embedded (FFPE) tissue is an ideal sample type for cancer biomarker analysis due to its ubiquitous use in cancer diagnosis in the clinic and consequent availability in oncology hospitals and clinics as well as biobanks. Biomarker discovery to date using FFPE have used only very few patient samples, making clinically relevant biomarker discovery difficult due to large patient-to-patient variation. As a part of our Biospecimen Research Network (BRN) program we funded a proteomic biomarker study of a large number of colorectal cancer and adjacent normal tissue samples. The investigators employed two platforms for biomarker discovery: label-free intensity based discovery using high resolution tandem mass spectrometry and targeted quantitation using multiple reaction monitoring. These two techniques allowed them to dig deeper into the proteome and to profile phosphopeptides. Paired tissue from 40 patients was profiled and of the 2875 proteins quantified, 367 proteins changed significantly in patients whose tumor size was greater than 50%. Large changes in secreted proteins were observed and many of these proteins were also observed in blood, offering promise for a potential blood-based biomarker for colorectal cancer. A blood-based biomarker assay for colorectal cancer could ultimately reduce the number of colonoscopies required, reducing cost and discomfort. Citation Format: Lokesh Agrawal, Fiona McAlister, Sushmita Roy, Florian Unger, Kerstin David, Harmut Juhl, Daniel Chelsky, Helen Moore. Proteomic changes observed in colon cancer tumors by label-free differential profiling of paired tumor versus normal FFPE samples. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1562. doi:10.1158/1538-7445.AM2015-1562