tbuckley/cabot-search huggingface dataset:
Evaluation of chemotherapy with cisplatin plus gemcitabine after failure of gemcitabine alone for unresectable or recurrent biliary tract cancer.
Authors: Ryo Kameda, Tomoko Ando, Satoshi Kobayashi, Makoto Ueno, Shinichi Ohkawa
Journal: Journal of Clinical Oncology (2012)

377 Background: As there was no standard chemotherapy for advanced biliary tract cancer before ABC-02, we had treated our patients with gemcitabine alone. However, recently cisplatin plus gemcitabine became standard as first line chemotherapy. We assessed the benefits of chemotherapy with cisplatin plus gemcitabine after failure of gemcitabine alone before ABC-02 era. Methods: We retrospectively examined the patients with advanced biliary tract cancer, who were treated with chemotherapy using cisplatin plus gemcitabine after failure of gemcitabine alone. The eligible patients had unresectable or recurrent biliary tract cancer, objective tumor progression after gemcitabine alone chemotherapy, adequate organ function including renal function and ECOG performance status (PS) 0-1. The treatment consisted of cisplatin (25 mg per square meter of body-surface area) plus gemcitabine (1000 mg per square meter) on days 1 and 8, every 3 weeks. Results: Between December 2010 and July 2011, 10 patients were enrolled. Their median age was 63 years, the male : female ratio was 8:2, intrahepatic bile ducts : gall bladder : extrahepatic bile duct 6:3:1, locally advanced : metastatic disease 1:9, PS0 : PS1 7:3. The objective response rate was 30%, and the tumor control rate was 60%. The median progression-free survival was 4.0 months (95% confidence interval (CI): 1.4-6.9 months) with median overall survival 6.4 months (95% CI: 3.7-7.6 months). Grade 3-4 toxicities were neutropenia (30%) and anemia (30%). Conclusions: Cisplatin plus gemcitabine can be an optional therapy for unresectable or recurrent biliary tract cancer after failure of gemcitabine alone.
Genome-wide analyses for personality traits identify six genomic loci and show correlations with psychiatric disorders
Authors: Min-Tzu Lo, David A Hinds, Joyce Y Tung, Carol Franz, Chun-Chieh Fan, Yunpeng Wang, Olav B Smeland, Andrew Schork, Dominic Holland, Karolina Kauppi, Nilotpal Sanyal, Valentina Escott-Price, Daniel J Smith, Michael O'Donovan, Hreinn Stefansson, Gyda Bjornsdottir, Thorgeir E Thorgeirsson, Kari Stefansson, Linda K McEvoy, Anders M Dale, Ole A Andreassen, Chi-Hua Chen
Journal: Nature Genetics (2016)
Sequential FDG-PET/CT as a surrogate marker of response to sunitinib in metastatic clear cell renal cancer.
Authors: T. Powles, S. Chowdhury, N. Avril, J. Bomanji, J. Shamash, N. Sarwar, A. Rockall, A. Sahdev, P. D. Nathan, I. Kayani
Journal: Journal of Clinical Oncology (2011)

301 Background: The purpose of this study was to investigate sequential FDG PET-CT as a correlative marker in metastatic clear cell renal cancer (mRCC) patients treated with first line sunitinib. Three sequential scans were performed to determine the importance of the timing of scans. Methods: Forty-four untreated mRCC patients with MSKCC intermediate risk and poor risk disease were enrolled into a prospective study. FDG PET-CT scans were performed before (n=44), after 4 weeks (n=43) and 16 weeks (n=40) of sunitinib given at standard doses as the translational aspect of this trial ( NCT01024205 ). The primary endpoint was to determine whether 18 F-FDG PET-CT response (defined as a 20% reduction in SUVmax) correlated with survival. Results: Forty-three (98%) patients had FDG PET-CT avid lesions at diagnosis (median SUVmax 6.8 range: &lt;2.5–18.4). In multivariate analysis a high SUVmax and increased number of PET positive lesions correlated with worse overall survival (OS) (HR: 3.30 (95%CI: 1.36–8.45) and 3.67 (95%CI: 1.43–9.39) respectively[p&lt;0.05]). After 4 weeks of sunitinib, metabolic responses occurred in 24 (57%) patients at 4 weeks, but this did not correlate with progression-free survival [PFS] (HR for responders= 0.87 [95%CI: 0.40–1.99]) or OS (HR for responders= 0.80 [95%CI: 0.34–1.85]) (p&gt;0.05 for both). After 16 weeks of treatment, FDG PET-CT demonstrated disease progression in 28% (n=12) patients. At this time point, the FDG PET-CT correlated with both OS and PFS (HR 5.96 [95%CI: 2.43–19.02] and HR 12.13 [95%CI: 3.72–46.45] respectively). Conclusions: Baseline FDG PET prior to sunitinib yields prognostically significant data. FDG PET response at 16 weeks predicts outcome, which is not the case at 4 weeks. This subsets of patients with a poor prognosis at 16 weeks could be investigated within the context of a randomized clinical trial. [Table: see text]
Hierarchical clustering analysis of tissue microarray immunostaining data on renal cell carcinomas.
Authors: L. M. Antón Aparicio, V. Medina Villaamil, R. García Campelo, G. Aparicio Gallego, I. Santamarina Caínzos, M. Haz Conde, L. Valbuena Rubira, E. Grande, M. Valladares Ayerbes
Journal: Journal of Clinical Oncology (2011)

393 Background: The clinical use of molecular expression profiles could result in more accurate and objective diagnoses of cancers as well as prognoses of disease or response to the treatment. Unsupervised hierarchical clustering (UHC) analysis is a common method to profile the molecular expression of tissue microarray data. Methods: TM4: a free, open-source system for microarray data management and analysis was used in order to identify expression patterns of interest in our cohort of renal cell carcinomas (RCC) (n=80). We investigated 5 pathological predictors: (a) the histological type, (b) Fuhrman grade, (c) depth of infiltration, (d) metastasis in lymph node, (e) TNM stages, and 27 immunohistochemical molecular predictors involved in different pathways of tumor development and progression including: p53 and VHL tumor suppressor proteins; Bcl-2 and Survivin antiapoptotic proteins; Hif1-alpha and Notch proteins as a transcription factors; EGFR, PDGFR-α and VEGF proteins involved in tumor growth and proliferation; Glut proteins involved in tumor cell metabolism. Results: Unfavorable prognosis was significantly correlated with pathological predictors. Clear RCC histological subtype had a worse prognosis than the other ones studied to be accompanied by increased expression of Hif1-alpha and CAIX (p&lt;0.001 in both cases) in patients with a number of metastatic nodes weighed (p&lt;0.001). We found in Fuhrman Grade III samples a higher expression of VEGF (p=0.029). UHC analysis was done using average method with Spearman rank test to group the data with different predictor profiles. A preliminary analysis by hierarchical clustering of RCC produced three separate clusters groups. Conclusions: UHC based on a extended immunoprofile might be a useful, promising and powerful tool for further translational studies and should lead us to define a diagnostic and prognostic signature for RCC. Our laboratory is currently involved in this issue. No significant financial relationships to disclose.
Micro <scp>RNA</scp> (miR)‐203 and miR‐205 expression patterns identify subgroups of prognosis in cutaneous squamous cell carcinoma
Authors: J. Cañueto, E. Cardeñoso‐Álvarez, J.L. García‐Hernández, P. Galindo‐Villardón, P. Vicente‐Galindo, J.L. Vicente‐Villardón, D. Alonso‐López, J. De Las Rivas, J. Valero, E. Moyano‐Sanz, E. Fernández‐López, J.H. Mao, A. Castellanos‐Martín, C. Román‐Curto, J. Pérez‐Losada
Journal: British Journal of Dermatology (2016)

Cutaneous squamous cell carcinoma (CSCC) is the second most widespread cancer in humans and its incidence is rising. These tumours can evolve as diseases of poor prognosis, and therefore it is important to identify new markers to better predict its clinical evolution.We aimed to identify the expression pattern of microRNAs (miRNAs or miRs) at different stages of skin cancer progression in a panel of murine skin cancer cell lines. Owing to the increasing importance of miRNAs in the pathogenesis of cancer, we considered the possibility that miRNAs could help to define the prognosis of CSCC and aimed to evaluate the potential use of miR-203 and miR-205 as biomarkers of prognosis in human tumours.Seventy-nine human primary CSCCs were collected at the University Hospital of Salamanca in Spain. We identified differential miRNA expression patterns at different stages of CSCC progression in a well-established panel of murine skin cancer cell lines, and then selected miR-205 and miR-203 to evaluate their association with the clinical prognosis and evolution of human CSCC.miR-205 was expressed in tumours with pathological features recognized as indicators of poor prognosis such as desmoplasia, perineural invasion and infiltrative growth pattern. miR-205 was mainly expressed in undifferentiated areas and in the invasion front, and was associated with both local recurrence and the development of general clinical events of poor evolution. miR-205 expression was an independent variable selected to predict events of poor clinical evolution using the multinomial logistic regression model described in this study. In contrast, miR-203 was mainly expressed in tumours exhibiting the characteristics associated with a good prognosis, was mainly present in well-differentiated zones, and rarely expressed in the invasion front. Therefore, the expression and associations of miR-205 and miR-203 were mostly mutually exclusive. Finally, using a logistic biplot we identified three clusters of patients with differential prognosis based on miR-203 and miR-205 expression, and pathological tumour features.miR-205 and miR-203 tended to exhibit mutually exclusive expression patterns in human CSCC. This work highlights the utility of miR-205 and miR-203 as prognostic markers in CSCC.
Megakaryocytes Support Viability Proliferation and Protection of Primary Pre-B ALL Cells from Chemotherapy
Authors: Stephanie Nicole Shishido, EunJi Gang, Ruth Xu, Hye Na Kim, Yann Duchartre, Steven D. Mittelman, Hisham Abdel-Azim, Matthew J Oberley, Nora Heisterkamp, Yong-Mi Kim
Journal: Blood (2015)
The Frequency and Management of Asparaginase-Related Thrombosis in Pediatric and Adult Patients with Acute Lymphoblastic Leukemia Treated On the Dana-Farber Cancer Institute (DFCI) Consortium Protocols.
Authors: Rachael F. Grace, Suzanne E. Dahlberg, Donna Neuberg, Stephen E. Sallan, Ellis J. Neufeld, Daniel J. DeAngelo, Lewis B. Silverman
Journal: Blood (2009)
Four Weeks Administration Schedule of Ropeginterferon Alfa-2b (AOP2014/P1101) in Polycythemia Very Patients Allows Maintaining of Efficacy with Favorable Toxicity Profile in the Phase I/II Peginvera Stud
Authors: Veronika Buxhofer-Ausch, Heinz Gisslinger, Josef Thaler, Ernst Schlögl, Gunther Gastl, Dominik Wolf, Robert Kralovics, Bettina Gisslinger, Sarita Ban, Alexander Egle, Thomas Melchardt, Sonja Burgstaller, Ella Willenbacher, Martin Schalling, Maria Theresa Krauth, Nicole C.C. Them, Michael Zörer, Oliver Ammann-Mwathi, Pavla Kadlecova, Oleh Zagrijtschuk, Christoph Klade, Richard Greil
Journal: Blood (2015)
Assessment of genetic predisposition to lymphedema.
Authors: J. M. Armer, B. R. Stewart
Journal: Journal of Clinical Oncology (2011)

195 Background: In the United States, 203,000 women are diagnosed annually with breast cancer (BC). Currently, over 2.3 million women in the United States are breast cancer survivors. With the increased incidence and survivorship, more women are living with the long-term treatment effects such as lymphedema (LE). We are nearing completion of stage one of a three-stage research project to examine genetic factors that potentially predispose BC survivors to develop LE. In stage one, we are working to identify novel genetic polymorphisms pointing to genomic regions and genes associated with LE risk. In stage two, we will use exome sequencing to examine both rare and common genetic variants potentially associated with variation in symptom manifestations of LE in breast cancer survivors; to examine phenotypic and genotypic variation in LE emerging following cancer treatment; and to examine associations between LE phenotypes among breast cancer survivors with LE and genomic factors and non-genomic factors. In stage three, we will replicate at the genetic level the associations detected. Methods: Institutional funding was obtained for a GWAS-design feasibility study with 96 breast cancer survivors with and without LE (48/48). Genetic material (from buccal swabs), limb volume (by perometry and circumferences), and self-reported LE-related symptoms were collected in one laboratory appointment. Results: Ninety-five percent of survivors participating in an on-going longitudinal study consented to participate in the genetic pilot (N=96). Buccal swabs provided yield for DNA extraction (concentration average 174.94 ng/ul). An additional 96 specimens have been collected for a second pilot GWAS (N =192). Conclusions: The pilot findings form the basis for a larger multisite proposed study to examine genetic predisposition to secondary LE. The findings of the larger study will lead to the design and timing of subsequent interventions aimed at reducing LE risk and improving overall survivorship quality of life. Findings concerning interactions among best cancer treatments and LE genetic predisposition will have the potential to guide the selection of cancer treatment to minimize complications when survival outcomes are equivalent across competing treatment approaches.
Tet2 Loss Accelerates The Myeloproliferative Neoplasm (MPN) Phenotype Of Jak2V617F Knockin Mice But Is Insufficient To Cause Leukemic Transformation
Authors: Edwin Chen, Lawrence J Breyfogle, Rebekka K. Schneider, Luke Poveromo, Ross L. Levine, Benjamin L. Ebert, Ann Mullally
Journal: Blood (2013)
Mesenchymal Stromal Cells (MSCs) Acquire Cardiac-Specific Markers but Do Not Become Functional Cardiomyocytes and Retain the Stromal Phenotype.
Authors: Robert A. Rose, Huije Jiang, Xing Hua Wang, Simone Helke, James N. Tsoporis, Nanling Gong, Stephanie C.J. Keating, Thomas G. Parker, Peter Bacx, Armand Keating
Journal: Blood (2007)
Comparison of indocyanine green (ICG) fluorescence imaging plus blue dye and blue dye alone in sentinel node navigation surgery (SNNS) for breast cancer.
Authors: A. Hirano, T. Shimizu, M. Kamimura, K. Ogura, N. Kim, Y. Setoguchi, F. Okubo, H. Inoue, R. Miyamoto, J. Kinoshita, K. Ogawa
Journal: Journal of Clinical Oncology (2011)

1108 Background: Invisible near-infrared (NIR) fluorescence imaging enables highly sensitive sentinel node navigation surgery (SNNS). A comparison was made between the results of a sentinel lymph node biopsy (SLNB) using indocyanine green (ICG) fluorescence imaging (FI) in combination with blue dye and those of SLNB using blue dye alone as a tracer. Methods: Five hundred one patients were underwent SLNB from 2005 to 2010. Sentinel lymph nodes (SLNs) were identified by injecting sulfan blue (SB) alone between 2005 and 2008 and through injection of SB in combination with ICG-FI from 2009 to 2010. After subareolar injection of ICG (5 mg) and SB (15 mg), fluorescence images of the subcutaneous lymph flow were obtained using Photodynamic Eye (Hamamatsu Photonics Co.). Results: A total of 393 patients underwent SLNB using SB alone as a tracer, while a total of 108 patients underwent SLNB using the combination method. The number of SLNs ranged from zero to five (1.6 on average) in patients receiving SB alone and from one to six (2.2 on average) in those undergoing combined SB-ICG. The SLN identification rate was significantly higher in the SB-ICG combination group than in the SB alone group (100% vs. 95.7%; p=0.0037). In the SB-ICG group, one patient was positive for SB alone, eight patients were positive for ICG alone, and the remaining 99 were positive for both SB and ICG. The number of patients who were positive for metastasis was 56 (14.2%) in the SB alone group and 16 (14.8%) in the SB-ICG group. In the SB-ICG group, metastases were observed in the ICG- and SB-positive SLNs in 10 patients, in the ICG-positive SLNs alone in five patients, and in the SB-positive SLNs alone in one patient. These results indicated the advantage of the use of ICG in combination with SB. The mean observation period was 779 days in the SB alone group and 213 days in the SB-ICG group. No patients experienced axillary recurrence in the SB-ICG group; however, such recurrence was detected in three patients (0.8%) in the SB alone group. Conclusions: ICG fluorescence imaging combined with SB injection is remarkably useful and is recommended particularly in the case where no radiotracers are available.
Decreased Expression of Nucleophosmin/B23 Increases Drug Sensitivity of Adriamycin-Resistant Lymphoblastic Leukemia Molt-4 Cells through mdr-1 Regulation
Authors: Jianda Hu, Lingyan Wang, Buyuan Chen, MinHui Lin, Yanqin Cao, Yingyu Chen, Xinji Chen, Tingbo Liu
Journal: Blood (2014)
Biological Databases for Hematology Research
Authors: Qian Zhang, Nan Ding, Lu Zhang, Xuetong Zhao, Yadong Yang, Hongzhu Qu, Xiangdong Fang
Journal: Genomics Proteomics & Bioinformatics (2016)

Abstract With the advances of genome-wide sequencing technologies and bioinformatics approaches, a large number of datasets of normal and malignant erythropoiesis have been generated and made public to researchers around the world. Collection and integration of these datasets greatly facilitate basic research and clinical diagnosis and treatment of blood disorders. Here we provide a brief introduction of the most popular omics data resources of normal and malignant hematopoiesis, including some integrated web tools, to help users get better equipped to perform common analyses. We hope this review will promote the awareness and facilitate the usage of public database resources in the hematology research.
Efficacy and safety of first-line bevacizumab (Bev) combined with paclitaxel (Pac): An observational study in 786 patients (pts) with HER2-negative metastatic breast cancer (mBC).
Authors: P. Klare, F. G. Foerster, M. Geberth, A. Schneeweiss, H. Tesch, S. Kuemmel, C. Schumacher, W. Hollburg, U. Soeling, M. Schmidt
Journal: Journal of Clinical Oncology (2011)

1079 Background: First-line Bev–Pac is an established treatment option in HER2-negative mBC, significantly improving progression-free survival (PFS) and response rate (RR) versus Pac alone. Two additional trials have demonstrated significantly improved PFS and RR with standard chemotherapy combined with Bev. The ATHENA study confirmed the good tolerability of Bev combined with chemotherapy. In Germany, a non-interventional study evaluated first-line Bev–Pac in the routine oncology practice setting. Methods: Bev–Pac was given according to the European label as first-line therapy to pts with HER2-negative mBC. Safety and efficacy data were collected for up to 1 year (or until progression, death, or Bev discontinuation, if earlier). Results: By Dec 2010, complete data were available for 786 pts. Baseline pt characteristics: median age, 58 years (range 26–87); age ≥65 years, 32%; disease-free interval <1 year, 24%; tumor grade 1/2/3/unknown (%), 2/49/39/5; triple negative, 19%; bone/liver/lung metastases (%), 54/43/34; ECOG status 0/1/2/3 (%), 39/47/8/1; prior endocrine therapy for mBC, 27%; prior (neo)adjuvant chemotherapy, 65% (24% taxane). The most common grade ≥3 clinical adverse events were: pain, 9.0% (all G3); hypertension, 5.0% (G3, 4.6%; G4, 0.4%); thrombosis/embolism, 1.4% (G3, 0.8%; G4, 0.3%; G5, 0.4%); sensory neuropathy, 2.7% (all G3); and infection, 1.1% (G3, 0.3%; G4, 0.4%; G5, 0.5%). Grade ≥3 proteinuria occurred in 0.5% of pts (G3, 0.4%); gastrointestinal perforation occurred in 0.8% (G4, 0.3%; G5, 0.5%). The RR was 62%, including complete responses in 11%. A further 20% had stable disease, 9% had progressive disease as best response, and 9% were not evaluable. By Dec 2010, PFS events had been recorded in 67% of pts. Median PFS was 9.3 months (95% CI 8.9–10.2). The 1-year survival rate was 73% (95% CI 70–77%). Median overall survival is immature (61% of pts still alive). Conclusions: The safety and efficacy of Bev–Pac in routine oncology practice is generally consistent with results from prospective randomized trials of 1st-line Bev-containing therapy and the ATHENA study. Follow-up is ongoing.
Making the Most of Cancer Surgery with Neoadjuvant Immunotherapy
Authors: Ignacio Melero, Pedro Berraondo, María E. Rodríguez-Ruiz, José L. Pérez-Gracia
Journal: Cancer Discovery (2016)

Surgery remains our strongest treatment pillar against early stages of cancer. In a number of instances, the curative potential of surgery can be enhanced by treatments given before (neoadjuvant) or after (adjuvant) surgical procedures. Immunomodulation has emerged as a powerful tool to fight metastatic disease across cancer histologies and goes now to be tested at earlier surgically amenable stages. The work by Liu and colleagues in this issue provides solid preclinical evidence in support of neoadjuvant immunotherapy over adjuvant approaches. Cancer Discov; 6(12); 1312-4. ©2016 AACRSee related article by Liu and colleagues, p. 1382.
The Small Molecule Img-98, a Potent and Selective Inhibitor of the Lysine Demethylase Lsd-1, Effectively Augments the Pro-Differentiation Effects of ATRA in a Pre-Clinical Model of AML
Authors: Ronan T. Swords, Aymee Perez, Ana Rodriguez, Justin M. Watts, Fernando Vargas, Roy Elias, Hugh Y. Rienhoff, Arthur Zelent
Journal: Blood (2015)
Mycobacterium chimaera infections associated with heater-cooler units (HCU): closing another loophole in patient safety
Authors: Marc J. Struelens, Diamantis Plachouras
Journal: Eurosurveillance (2016)

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Systematic comparison of tumor phenotype in primary breast cancer versus corresponding lymph nodes and disease recurrences: Results of the retrospective multicenter WSG/DETECT PriMet study.
Authors: C. Liedtke, O. Gluz, F. Heitz, R. Wuerstlein, R. E. Kates, J. Tio, U. Nitz, A. Du Bois, T. N. Fehm, N. Harbeck
Journal: Journal of Clinical Oncology (2011)

1038 Background: Estrogen receptor (ER), progesterone receptor (PR), and HER2 expression define clinically relevant breast cancer subtypes. The triple negative breast cancer (TNBC) phenotype is characterized by an unfavorable prognosis. The clinical significance of phenotype changes between primary tumor (PT), lymph nodes (LN), and disease recurrence (DR) is unclear. Methods: PriMet, a retrospective multicenter (n=11) study was designed to compare BC phenotype in PT and corresponding DR including patients with unilateral BC with subsequent/synchronous local/regional/distant DR. Our aim was to evaluate discordance rates between PT/DR, analyze the impact of discordance on patient outcome, and compare concordance in PT/LN to concordance in LN/DR. Results: 436 patients were entered into PriMet. Triple receptor status for PT and DR was available in 377 patients; 68 patients showed TNBC in PT, 40 patients (58.8 %) had TNBC in both PT and DR (i.e. TNBC persistence); 28 patients (17.7 %) changed from TNBC to non-TNBC (15 became HER2 positive (4.0 %)). Status changes for ER and PR were significantly positively associated (p<0.001). Significant differences regarding PRS and DFS were observed in both univariate and multivariate analysis. Mean PRS was 30.0 vs. 85.0 months for persistent TNBC vs non-TNBC. PRS for discordant cases was 59.9 months (non-TNBC/TNBC) 21.9 months (TNBC / non-TNBC without HER2 overexpression) and 57.2 months (TNBC / non-TNBC with HER2 overexpression). In a subset of patients (n=20) tumor phenotype results in corresponding LNs are already available. In 60 % discordance regarding triple receptor expression was observed. In 75% of discordant cases, discordance was observed between PT/LN; in 25% discordance was observed between LN/DR. Conclusions: Our results provide evidence regarding phenotype changes in PT vs. LN/DR and underline the importance of immunohistochemical DR verification. Con-/discordance of breast cancer phenotype was significantly associated with adverse patient outcome. Phenotypic changes appear to be an early event in the metastatic cascade.