tbuckley/cabot-search huggingface dataset:
Abstract 5007: Differential expression of neurogenes among breast cancer subtypes identifies high risk patients
Authors: Mario Mancino
Journal: Cancer Research (2016)

Abstract The nervous system is now recognized to be a relevant component of the tumor microenvironment. Receptors for neuropeptides and neurotransmitters have been identified in breast cancer. However, very little is known about the role of neurogenes in regulating breast cancer progression. Our purpose was to identify neurogenes associated with breast cancer tumorigenesis with a potential to be used as biomarker and/or targets for treatment. We used three databases of human genes: GeneGo, GeneCards and Eugenes to generate a list of 1266 relevant neurogenes. Then we used bioinformatics tools to interrogate two published breast cancer databases SAGE and MicMa (n = 96) and generated a list of 7 neurogenes that are differentially express among breast cancer subtypes. The clinical potential was further investigated using the GOBO database (n = 1881). We identified 6 neurogenes that are differentially expressed among breast cancer subtypes and whose expression correlates with prognosis. Histamine receptor1 (HRH1), neuropilin2 (NRP2), ephrin-B1 (EFNB1), neural growth factor receptor (NGFR) and amyloid precursor protein (APP) were differentially overexpressed in basal and HER2-enriched tumor samples and syntaxin 1A (STX1A) was overexpressed in HER2-enriched and luminal B tumors. Analysis of HRH1, NRP2, and STX1A expression using the GOBO database showed that their expression significantly correlated with a shorter overall survival (p&amp;lt;0.0001) and distant metastasis-free survival (p&amp;lt;0.0001). In contrast, elevated co-expression of NGFR, EFNB1 and APP was associated with longer overall (p&amp;lt;0.0001) and metastasis-free survival (p&amp;lt;0.0001). We propose that HRH1, NRP2, and STX1A can be used as prognostic biomarkers and therapeutic targets for basal and HER2-enriched breast cancer subtypes. Citation Format: Mario Mancino. Differential expression of neurogenes among breast cancer subtypes identifies high risk patients. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5007.
Abstract 481: Low-molecular-mass secretome profiling identifies prognostic biomarkers for oral cavity squamous cell carcinomas
Authors: Kai-Ping Chang, Jau-Song Yu
Journal: Cancer Research (2016)

Abstract The profiling of cancer cell secretomes is considered to be a good strategy for identifying cancer- related biomarkers, but few studies have focused on identifying low-molecular-mass (LMr) proteins (&amp;lt;15 kDa) in cancer cell secretomes. Here, we used tricine-SDS-gel-assisted fractionation and LC-MS/MS to systemically identify LMr proteins in the secretomes of five oral cavity squamous cell carcinoma (OSCC) cell lines. Cross-matching of these results with nine OSCC tissue transcriptome datasets allowed us to identify 33 LMr genes/ proteins that were highly upregulated in OSCC tissues and secreted/released from OSCC cells. Immunohistochemistry and quantitative real-time PCR were used to verify the overexpression of two candidates, HMGA2 and MIF, in OSCC tissues. The overexpressions of both proteins were associated with cervical metastasis, perineural invasion, deeper tumor invasion, higher overall stage, and a poorer prognosis for post-treatment survival. Functional assays further revealed that both proteins promoted the migration and invasion of OSCC cell lines in vitro. Collectively, our data indicate that the tricine-SDS-gel/LC-MS/MS approach can be used to efficiently identify LMr proteins from OSCC cell secretomes, and suggest that HMGA2 and MIF could be potential tissue biomarkers for OSCC. Citation Format: Kai-Ping Chang, Jau-Song Yu. Low-molecular-mass secretome profiling identifies prognostic biomarkers for oral cavity squamous cell carcinomas. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 481.
Four routinely recorded parameters define four distinct prognostic groups in AML.
Authors: J. R. Novotny, H. Nueckel, A. Aisenbrey, U. Duehrsen
Journal: Journal of Clinical Oncology (2010)

6584 Background: Prediction of outcome in AML is crucial for patient counselling and therapy allocation. While numerous factors have been studied, they should be easily accessible for routine application. The best established prognostic factors are karyotype and age. However, performance status as measured by the ECOG may play an important role in the outcome of AML. Methods: 198 consecutive patients with AML were retrospectively analysed, irrespective of the applied therapy. Median age was 62 years (range 20-81) with approximately even sex distribution (95 male). Karyotype was 11.6 % good (score 0), 68.0 intermediate (score 1) and 20.4 % poor risk (score 3), respectively. The median survival was 382 days. The criteria of the Eastern Collaborative Oncology Group performance score (ECOG) were applied. Age older than 60 years and secondary leukemia were scored with 1 point, respectively. Patients were classified into four prognostic groups according to cumulative score, namely very good (0), good (1), poor (2-3) and very poor (≥ 4). Survival was calculated and plotted as Kaplan-Meier diagrams and binomial logistic regressionanalysis was done using the SPSS 17 statistic package. Results: In binomial logistic regressionanalysis the ECOG score was an independent prognostic factor (p = 0.007). The combined score separated clearly the four prognostic groups. In the small very good prognosis group all five patients survived. In the good prognosis group the median survival was not reached with a five year overall survival of 66 percent. In the poor prognosis group the median survival was 434 days with a five yeear survivasl of 28 percent. Finally in the very poor prognosis group the median survival was 97 days only with only 6 percent long term survival. Conclusions: Our findings show that the addition of the ECOG score defines four groups with very distinct prognosis, at least in our cohort. We extend previous findings. Firstly, our analysis includes 90 patients younger than 60 years and was not restricted to patients older than 60 years. Secondly, we showed that performance status is an independent predictor for survival. and should be studied prospectively to clarify its use for stratification in therapeutic studies. No significant financial relationships to disclose.
Stathmin-1 as a potential therapeutic target in urinary bladder cancer.
Authors: Ulrika Segersten, Tammer Hemdan, Marten Lindén, Sara Bergstrom Lind, Arvind Venkat Namuduri, Evelina Sjostedt, Teresita Diaz de Stahl, Anna Asplund, Per-Uno Malmstrom
Journal: Journal of Clinical Oncology (2014)

4535 Background: The oncoprotein-18/stathmin 1 (STMN1), involved in cell cycle progression and cell migration, has been reported to be expressed in several types of cancer, and is associated with clinical outcome in e.g. breast and liver cancer. The aims in this study were to investigate the clinical significance of STMN1 and to examine if STMN1 might be a possible therapeutic target in urinary bladder cancer. Methods: Immunohistochemical analyses of STMN1 protein expression were performed in three urinary bladder cancer cohorts; cohort I (115 Ta-, 115 T1-, 112 T2-4-tumors), a validation cohort II (236 T2-T4 tumors) based on randomized controlled trials and a metastatic primary tumor/matched metastasis-material (90 patients). In the urinary bladder cancer cell line, T24, the effect of STMN1 on cell proliferation and migration was evaluated by inhibiting the cellular expression of STMN1 using STMN1-siRNA. Results: Patients with T1- or muscle-invasive disease exhibiting high expressionof STMN1 had shorter overall survival (OS) and disease specific survival (DSS). In multivariate analysis, adjusting for stage, age and gender, the results were for T2-T4 patients: OS (HR=1.77 95% CI 1.02-3.07; p=0.04) and DSS (HR=2.04 95% CI 1.13-3.68; p=0.02); for T1-4 patients: DSS (HR=1.83 95% CI 1.09-3.08; p=0.02). The higher risk of cancer death within 2 years for T2-T4 patients with high STMN1-expressing tumors was validated in cohort II (HR= 1.76 95% CI 1.04 -2.99; p=0.03). In the metastatic bladder cancer material, 69% of the patients with one metastasis and 75% of the patients with several matched metastases were STMN1-positive in both the primary tumor and matched metastases. Moreover, the ability of the urinary bladder cancer cell line to grow or migrate was significantly reduced, (p<0.01 respectively p<0.0001) when transfecting the cells with a siRNA targeting STMN1. Conclusions: Our results suggest that STMN1 protein-expression has a potential both as a prognostic marker and a novel treatment target in urinary bladder cancer.
The benefits and side-effects of ramped hypertonic sodium dialysis.
Authors: F Locatelli, S Andrulli, S Di Filippo
Journal: Journal of the American Society of Nephrology (1996)

Journal of the American Society of Nephrology : JASN 7(12):p 2704-2706, December 1996. | DOI: 10.1681/ASN.V7122704
Scaled up general practice organisations do not provide better quality of care, report says
Authors: Matt Limb
Journal: BMJ (2016)

General practices that pool their resources in bigger partnerships or by working together in federations may see some gains in operational efficiency and prescribing but there were few signs that this “scaling up” had improved the quality of patient care, a study by the Nuffield Trust has said.

The 15 month study showed that three quarters of practices were now involved in bigger partnerships or federations, but that this had not boosted performance against a range of quality indicators and that patient satisfaction had fallen.1

The report’s authors called for a “phased introduction” of alternative contract models for large scale general practice organisations and integration with community providers, citing “insufficient evidence that large scale general practice will deliver high quality, cost effective care that is valued by patients.”2

Rebecca Rosen, senior Nuffield Trust fellow, said that, while large scale …
Abstract 4724: Novel and selective inhibitors of histone deacetylases (HDAC) 1 and 2 synergize with DNA methyltransferase inhibitor azacitidine in acute myeloid leukemia (AML)
Authors: Chengyin Min, Steven N. Quayle, Pengyu Huang, Jeffrey R. Shearstone, Simon S. Jones, Min Yang
Journal: Cancer Research (2016)

Abstract AML is a heterogeneous group of hematopoietic stem cell disorders characterized by defects in myeloid differentiation and increased proliferation of neoplastic hematopoietic precursor cells. Outcomes for patients with AML remain generally poor, highlighting the need for novel treatment options. Aberrant epigenetic regulation plays an important role in the pathogenesis of AML, and the DNA methyltransferase inhibitor VIDAZA™ (azacitidine) is approved by European Medicines Agency for the treatment of elderly patients with AML. Numerous clinical studies are ongoing to investigate the benefit of combining azacitidine with other investigational agents in AML. HDAC inhibitors are promising agents for the treatment of AML. Combination studies with HDAC inhibitors plus DNA methyltransferase inhibitors have suggested beneficial clinical activity in AML. However, the toxicity profiles of non-selective HDAC inhibitors in the combination settings limit the clinical benefit. In this work, we describe the preclinical development of highly selective HDAC inhibitors, which are hypothesized to have improved safety profiles than non-selective HDAC inhibitors, for combination therapy in AML. We demonstrate that selective HDAC1/2 inhibitors are highly effective and efficacious both as single agents and in combination with azacitidine in preclinical models of AML, including established AML cell lines, bone marrow samples freshly derived from AML patients and in vivo xenograft models of human AML. At the molecular level, gene expression profiling, DNA methylation mapping and chromatin immunoprecipitation analysis were performed on AML cells treated with either an HDAC1/2 inhibitor, azacitidine, or the drug combination. Molecular signatures and genes involved in myeloid cell differentiation, apoptosis and cell cycle arrest were identified as potential mediators of the combinatorial effects of HDAC1/2 inhibition with azacitidine. Together, these findings support the clinical evaluation of selective HDAC1/2 inhibitors in combination with azacitidine in AML patients. Citation Format: Chengyin Min, Steven N. Quayle, Pengyu Huang, Jeffrey R. Shearstone, Simon S. Jones, Min Yang. Novel and selective inhibitors of histone deacetylases (HDAC) 1 and 2 synergize with DNA methyltransferase inhibitor azacitidine in acute myeloid leukemia (AML). [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4724.
Structure-Based Drug Design of c-Kit Inhibitors for Use in the Treatment of Acute Myeloid Leukemia.
Authors: David S. Maxwell, Ashutosh Pal, Zhenghong Peng, Alexandr Shavrin, Stefan Faderl, David Harris, Quin Van, Zhiming Liu, Srdan Verstovsek, Taghi Manshouri, Alessandra Ferrajoli, Hagop M. Kantarjian, Zeev Estrov, William G. Bornmann
Journal: Blood (2006)
NCCN Guidelines Insights: Malignant Pleural Mesothelioma, Version 3.2016
Authors: David S. Ettinger, Douglas E. Wood, Wallace Akerley, Lyudmila A. Bazhenova, Hossein Borghaei, David Ross Camidge, Richard T. Cheney, Lucian R. Chirieac, Thomas A. D'Amico, Thomas Dilling, Michael Dobelbower, Ramaswamy Govindan, Mark Hennon, Leora Horn, Thierry M. Jahan, Ritsuko Komaki, Rudy P. Lackner, Michael Lanuti, Rogerio Lilenbaum, Jules Lin, Billy W. Loo, Renato Martins, Gregory A. Otterson, Jyoti D. Patel, Katherine M. Pisters, Karen Reckamp, Gregory J. Riely, Steven E. Schild, Theresa A. Shapiro, Neelesh Sharma, Scott J. Swanson, James Stevenson, Kurt Tauer, Stephen C. Yang, Kristina Gregory, Miranda Hughes
Journal: Journal of the National Comprehensive Cancer Network (2016)

These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines for Malignant Pleural Mesothelioma (MPM). These NCCN Guidelines Insights discuss systemic therapy regimens and surgical controversies for MPM. The NCCN panel recommends cisplatin/pemetrexed (category 1) for patients with MPM. The NCCN panel also now recommends bevacizumab/cisplatin/pemetrexed as a first-line therapy option for patients with unresectable MPM who are candidates for bevacizumab. The complete version of the NCCN Guidelines for MPM, available at NCCN.org, addresses all aspects of management for MPM including diagnosis, evaluation, staging, treatment, surveillance, and therapy for recurrence and metastasis; NCCN Guidelines are intended to assist with clinical decision-making.
Abstract LB-264: Landscape of tumor-infiltrating T-cell repertoire of human cancers
Authors: Bo Li, Taiwen Liu, Binbin Wang, Jinzeng Wang, Sachet Shukla, Ruoxu Dou, Stephen Hodi, Catherine Wu, Nir Hacohen, Jun Liu, X. Shirley Liu
Journal: Cancer Research (2016)

Abstract T cells play a critical role in antitumor immunity and are the primary targets in many immunotherapies. However, the study of tumor-infiltrating T cells has been complicated by the extremely diverse repertoire of T cell receptors, characterized by the complementarity determining region 3 (CDR3). Here using our newly developed algorithm, we studied the CDR3 sequences of tumor infiltrating T cells in 9,142 RNA-seq samples across 29 diseases. In total, we assembled over 600 thousands CDR3 sequences, covering the α, β, γ, δ chains. TRBV genes usage, CDR3 sequence length and conservation of infiltrating T cells resembled those in the peripheral blood of healthy donors in many tumors, except brain and kidney cancers. About 20% of the CDR3 calls were shared in multiple individuals. T cell clonotypes carrying these CDR3 sequences are known as the ‘public T cells’. In this work, we found that public T cell CDR3 amino acid (AA) sequences are shorter compared to the private ones and the middle 3 positions of the private CDR3 sequences were enriched for hydrophobic AAs. This finding potentially suggests that private T cell clonotypes in the tumors have greater potential to recognize neoantigens. We defined clonotype per kilo-reads (CPK) to measure the diversity of T cell repertoire and identified a strong positive association between CPK and tumor mutation load, implying that neoantigens may diversify the infiltrating T cell population. In addition, we predicted SPAG5 and TSSK6 as putative immunogenic cancer/testis antigens in multiple cancers based on their strong associations with CPK. Finally, we identified 3 potential immunogenic somatic mutations based on their co-occurrence with CDR3 sequences. One of them, PRAMEF4 F300V, was predicted to bind strongly to both MHC-I and MHC-II, with matched HLA types in its carriers. Our analyses have the potential to simultaneously identify immunogenic neoantigen and the tumor-reactive T-cell clonotype. Citation Format: Bo Li, Taiwen Liu, Binbin Wang, Jinzeng Wang, Sachet Shukla, Ruoxu Dou, Stephen Hodi, Catherine Wu, Nir Hacohen, Jun Liu, X. Shirley Liu. Landscape of tumor-infiltrating T-cell repertoire of human cancers. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-264.
Management of Venous Thromboembolism (VTE) in Patients with Acute Leukemia: Results from a Multicenter Study
Authors: Mariasanta Napolitano, Luca Valore, Giorgia Saccullo, Alessandra Malato, Calogero Vetro, Maria Enza Mitra, Alessandro Lucchesi, Francesco Fabbiano, Donato Mannina, Alessandra Casuccio, Maria Ilaria Del Principe, Anna Candoni, Francesco Di Raimondo, Sergio Siragusa
Journal: Blood (2014)
Abstract 4211: Discovery of a novel peptide for improvement of radiotherapeutic efficacy and development of prognotic diagnosis
Authors: Kyoung Jin Lee, Jae Hee Lee, Si Yeol Song, Seong-Yun Jeong, Eun Kyung Choi
Journal: Cancer Research (2016)

Abstract Cancer can be treated by the various modalities including surgery, chemotherapy, radiotherapy, among which the radiotherapy is the most important therapeutics in the cancer treatment. Despite the progression of modalities, cancer therapy has been constrained by impasse of prediction of treatment outcome and direction of cancer therapeutics because of diagnosis date, metastasis and genetic diversity of the individual patients. In this study, we discovered specific tumor targeting peptides and radiotherapy-responding peptides suitable to apply to cancer therapy and monitoring of radiotherapy response. For a non-invasive imaging for potential cancer diagnosis system, we screened peptides using the phage display technique. Phage display is used in various pharmaceutical biotechnologies, and the one of the most powerful technologies to identify novel peptides regulating carcinogenesis. To emphasize the function of peptide ligands in a living body and consider the tumoral microenvironment, we used the patient-derived xenograft (PDX) tumor models for in vivo peptide displayed phage screening. It is warranted that the peptides specifically targeting in vivo human cancer xenografts with radiation treatment or not in colorectal cancer PDXs. We performed in vivo peptide screening in the two different cases of colorectal cancer PDX mouse models, and selected peptides were confirmed to radiation responding peptides and radiation resistant peptides. The results suggested that selected peptides were a promising diagnostic lead molecule for rapid and accurate detection for the radiotherapy response. Taken together, we described a strategy to identify the peptides by in vivo phage display, and peptides possessed the specific targeting ability which would be potentially feasible for the development of personalized precision treatment. Its might be potential IR-guided probe and prognostic diagnosis in radiotherapy for colorectal cancer. Keywords: Peptide, Colorectal cancer, Patient-derived xenograft (PDX), Radiation, In vivo peptide screening Citation Format: Kyoung Jin Lee, Jae Hee Lee, Si Yeol Song, Seong-Yun Jeong, Eun Kyung Choi. Discovery of a novel peptide for improvement of radiotherapeutic efficacy and development of prognotic diagnosis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4211.
Whole Brain Radiotherapy for Brain Metastases
Authors: Orit Kaidar-Person, Carey K. Anders, Timothy M. Zagar
Journal: JAMA (2016)

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Robot-assisted Surgery for Benign Ureteral Strictures: Experience and Outcomes from Four Tertiary Care Institutions
Authors: Nicolò Maria Buffi, Giovanni Lughezzani, Rodolfo Hurle, Massimo Lazzeri, Gianluigi Taverna, Giorgio Bozzini, Riccardo Bertolo, Enrico Checcucci, Francesco Porpiglia, Nicola Fossati, Giorgio Gandaglia, Alessandro Larcher, Nazareno Suardi, Francesco Montorsi, Giuliana Lista, Giorgio Guazzoni, Alexandre Mottrie
Journal: European Urology (2016)