tbuckley/cabot-search huggingface dataset:
Associations of Aberrant T Cell Antigen Expression on B Cells of Diffuse Large B Cell Lymphoma Patients with Their Background and Prognosis
Authors: Yuhko Suzuki, Tsutomu Yoshida, Hirokazu Kimura, Manabu Ohsaka, Koji Miyazaki, Mikio Danbara, Ryouichi Horie, Yuhichi Satoh, Masaaki Higashihara
Journal: Blood (2010)
Biosimilar Compared with Originator Filgrastim for Autologous Stems CELL Mobilisation: A Prospective-Historical Control Study in Multiple Myeloma REAL-Life Setting
Authors: Massimo Martino, Tiziana Moscato, Iolanda Donatella Vincelli, Francesca Ronco, Roberta Fedele, Giuseppe Irrera, Giuseppe Console, Giuseppe Messina, Eugenio Piro, Stefano Molica, Fortunato Morabito
Journal: Blood (2014)
SiRNA-mediated in vivo gene knockdown by acid-degradable cationic nanohydrogel particles
Authors: Nadine Leber, Leonard Kaps, Misbah Aslam, Jonathan Schupp, Alexander Brose, David Schäffel, Karl Fischer, Mustafa Diken, Dennis Strand, Kaloian Koynov, Andrea Tuettenberg, Lutz Nuhn, Rudolf Zentel, Detlef Schuppan
Journal: Journal of Controlled Release (2016)
Oral paricalcitol (19-nor-1,25-Dihydroxyvitamn D<sub>2</sub>) in women with metastatic breast cancer receiving taxanes or ixabepilone: A feasibility trial.
Authors: J. Lawrence, J. Lovelace, S. A. Akman, S. A. Melin, L. D. Case, G. Schwartz
Journal: Journal of Clinical Oncology (2011)

1120 Background: The active form of vitamin D (1,25(OH)2D) affects proliferation, apoptosis, and angiogenesis and is a potential therapy for breast cancer. However, the use of active vitamin D is limited by hypercalcemia. Analogs of 1,25(OH)2D that are less calcemic have been developed for the treatment of hyperparathyroidism of kidney disease. In preclinical studies, 1,25(OH)2D analogs improved on the clinical efficacy of taxanes. Methods: We sought to determine the safety of dose titration of the 1,25(OH)2D analog, paricalcitol (19-nor-1,25-Dihydroxyvitamin D2), in combination with a taxane or ixabepilone in the treatment of women with metastatic breast cancer (MBC). Feasibility was defined as 8 weeks of continuous therapy of paricalcitol in the first 3 months. Serum calcium was monitored weekly until a steady dose was achieved. If the serum calcium was < 8.9 mg/dl then the dose was increased by one tablet (1 µg), if 9-11.4 mg/dl the dose maintained, and at higher levels the dose was held. Results: We enrolled 16 women with MBC and an ECOG of ≤1. Eligibility requirements included a corrected serum calcium < 10.5 mg/dl. Three women had bone metastasis. Of those enrolled, 69% took 8 weeks of continuous therapy. The starting dose was 2µg/day. Sixty-four percent of patients were able to escalate the dose. The maximum hypercalcemia was grade 1 experienced by 4 patients. Five patients had hypovitaminosis D at baseline (25 -Hydroxyvitamin D [25-OHD] D levels < 20ng/ml). The median parathyroid hormone (PTH) level at baseline was 81.0 pg/ml (67-173) in the 5 patients with hypovitaminosis D vs 56.0 pg/ml (24-94) for those with higher levels of baseline 25OH vitamin D (p =0 .01) (PTH reference 12-72 pg/ml). The PTH levels declined more over the initial 12 weeks in the patients with the lower 25OH Vitamin D levels at baseline (median declines of 50 vs 21, p =0 .04). The dose range of paricalcitol taken in the women enrolled was 2-7ug/day. Paricalcitol was well tolerated with no instances of hypercalcemia grade 2 or greater in this group of women with MBC. Conclusions: We conclude that paricalcitol is feasible in women who are receiving a taxane or ixabepilone in the metastatic setting and causes a decline in PTH.
Use of topoisomerase II alpha (TOP2A) protein overexpression to predict response to anthracycline-based chemotherapy.
Authors: S. Chan, J. S. Reis-Filho, P. D. Dickinson, P. Moseley, A. R. Green, I. O. Ellis, T. M. A. Abdel-Fatah
Journal: Journal of Clinical Oncology (2011)

1027 Background: Recent studies have suggested a link between levels of TOP2A expression, carcinogenesis and response to anthracycline based chemotherapy. It has been postulated that this relationship may be due the co-amplification of the HER2 and TOP2A genes. Some investigators have suggested that evaluation of TOP2A protein level may be more useful than gene alterations. Methods: In this study, the gene copy number using in-situ hybridization and protein expression using immunohistochemistry of both TOP2A and HER2 were evaluated in four independent series of breast cancers (BC): a) 240 locally advanced primary BC treated with anthracycline-based combination with or without taxane followed by surgery; pathological complete response (pCR) was used as the study end point, b) 245 BC in which all patients were primarily treated with surgery followed by anthracycline-based chemotherapy, c) 145 primary BC overexpressing HER-2 treated with surgery followed by trastuzumab and d) 2000 consecutive cases of primary BC in which adjuvant CMF and/or Tamoxifen therapies were prescribed. The association between gene and protein alteration of TOP2A and clinicopathological outcomes was determined. Results: In patients who received CMF chemotherapy and/or Tamoxifen, TOP2A protein overexpression was associated with HER2 amplification/overexpression (p=0.02), p53 mutation (p=0.03), a high mitotic index (p=0.01) and high proliferation index (p=0.04), but did not show any association with outcome. In patients who received anthracycline based treatment TOP2A gene amplification predicted a better disease free survival (p=0.026). In the anthracycline-based neoadjuvant chemotherapy series, the pCR rate was 31/132 (24%) in tumours expressing high levels of Topo2A, compared to 3/49 (6%) in tumours expressing low levels of Topo2A. (p=0.008). In multivariate analysis, TOP2A expression was an independent predictor for pCR (p<0.01). Conclusions: Alterations in TOP2A protein are an independent predictor of response to anthracycline based treatment in both the adjuvant and neoadjuvant setting. TOP2A overexpression could be a marker of high proliferative tumours.
Survival differences in metastatic bladder cancer by geography.
Authors: Rakesh Mandal, Binay Kumar Shah
Journal: Journal of Clinical Oncology (2012)

314 Background: It is unknown if there is any geographical variation in survival among patients with bladder cancer. This study was conducted to evaluate the survival rates in the northern (latitude ≥40 o ) and southern regions (latitude &lt; 40 o ) in the United States for the period of 2000-2008. Methods: We used Z-test in the Surveillance, Epidemiology, and End Results (SEER*Stat) program to analyze 1-year and 5-year relative survival rates of bladder cancer patients included in SEER database. Several cohorts categorized by race, gender, and age groups (&lt;60 and ≥60 years) were examined to compare the survival rates in the northern and southern regions of the U.S. Based on the counties’ centroid, northern (latitude ≥40 o ) and southern (latitude &lt; 40 o ) regions were determined. Results: The dataset comprised 6,501 and 664 patients with AJCC stage-IV bladder cancer among Caucasian and African Americans respectively. Among Caucasian men (&lt;60 years), 1-year survival rates in the northern and southern regions were 66.2± 2.5% (n=372) and 57.5± 1.9% (n= 738) respectively. Similarly, 5-year year survival rates in the northern and southern regions were 27.5± 2.6% (n=372) and 20.1± 1.7% (n= 738) respectively. Thus the survival for this group was lower in the South compared to the North and was statistically significantly (1-year: Z-value = -2.723, p= 0.006; 5-year: Z-value = -2.909, p= 0.003). There was no significant difference in the survival rates among any other cohorts examined. Conclusions: Caucasian men (&lt;60 year) with stage IV bladder cancer had lower 1- or 5-year relative survival rates in the South compared to the North. The survival difference in young Caucasian men with bladder cancer by geography may be due to differences in tumor biology resulting from the differential exposure to environmental carcinogens.
Nipple-sparing mastectomy and immediate breast reconstruction: Critical appraisal of five-year, single-center outcomes.
Authors: D. Westbroek, K. Mann, M. Ho, I. Gukas, I. Karat, R. Daoud, I. J. Laidlaw
Journal: Journal of Clinical Oncology (2011)

99 Background: Approximately 5,000 patients undergo breast reconstruction annually in the United Kingdom (2:1 ratio of immediate versus delayed respectively). Preservation of the breast envelope, i.e., skin and nipple areola complex (NAC) improves cosmesis. While skin-sparing mastectomy is an accepted modality for local control in appropriately selected patients, nipple-sparing mastectomy (NSM) remains controversial. In over 1,800 published NSM cases, the local event rate attributable to NAC preservation following NSM (therapeutic and prophylactic) is 0.16% with no evidence of deleterious impact on disease-free survival. In our cohort, patient selection criteria included: preoperative lesion characterisation; 5-mm margin acceptance; submission of separate nipple core specimens for paraffin block histological assessment and re-excision of all involved margins. This study is intended to evaluate the efficacy of loco-regional control in a consecutive cohort of patients, under uniform conditions undergoing nipple-sparing mastectomy and immediate breast reconstruction. We highlight the surgical technique used and propose in/exclusion criteria for appropriate patient selection. Methods: 84 consecutive patients underwent NSM and IBR at Frimley Park Hospital, Surrey, UK (IJL, RD) between January 2004 and December 2008. Data was accrued retrospectively from the institution’s clinical coding, electronic records, and WinPath database. Endpoints recorded include: the incidence of (occult) malignancy at the nipple margins; NAC subcutaneous tissue loss; local (NAC) recurrence rates and disease free survival. Results: The mean age was 51.1 years and follow-up 4.9 years. There was one case of local recurrence in a patient who declined re-excision of close/involved margins. The immediate peri-operative complication rate was within the national mastectomy breast reconstruction audit outcome guidelines. Conclusions: In appropriately selected patients, our findings support nipple preservation at the time of mastectomy and immediate reconstruction as this enhances the cosmetic outcome without compromising oncologic safety.
RAS, KIT and FLT3 Gene Mutations in inv(16)/t(16;16)-Positive Acute Myeloid Leukemia (AML): Incidence and Relevance on Clinical Outcome.
Authors: Juan Du, Richard F. Schlenk, Andrea Corbacioglu, Marianne Habdank, Claudia Scholl, Stefan Frohling, Lars Bullinger, Arnold Ganser, Hartmut Dohner, Konstanze Dohner
Journal: Blood (2006)
The role of HGF/c-MET signaling pathway in lymphoma
Authors: Bao Quoc Lam, Lu Dai, Zhiqiang Qin
Journal: Journal of Hematology & Oncology (2016)

Inappropriate activation of c-mesenchymal-epithelial transition (MET), the receptor tyrosine kinase (RTK) for hepatocyte growth factor (HGF), has been implicated in tumorigenesis and represented a promising therapeutic target for developing anticancer agents. In contrast to other solid tumors, there are limited data describing the functional role of HGF/c-MET signaling pathway in lymphoma. In the current review, we summarize recent findings about the expression, cellular mechanisms/functions, and therapeutic application of HGF/c-MET in different types of lymphoma, especially B cell lymphoma, T and NK cell lymphoma, and Hodgkin lymphoma. We also discuss the existing problems and future directions about studying the HGF/c-MET pathway in lymphoma cells.
Abstract 153: Inhibition of the 5-a-reductase Reduces Cardiac Hypertrophy and Improves Cardiac Function
Authors: Carolin Zwadlo, Natali Froese, Johann Bauersachs, Joerg Heineke
Journal: Circulation Research (2013)

Objectives: Left ventricular hypertrophy (LVH) is an independent risk factor for increased cardiovascular mortality and a precursor of heart failure. Gender-specific differences point to a pivotal role of androgens in the development of pathological LVH. Dihydrotestosterone (DHT) is metabolized from testosterone via the enzyme 5-α-reductase. The 5-α-reductase is upregulated in the hypertrophied myocardium, leading to our assumption that DHT rather than testosterone is the crucial component in the development of LVH and might therefore constitute a potential therapeutic target. Methods: One week after transverse aortic constriction (TAC) or sham surgery male wild-type mice were treated for 2 weeks via an oralgastric tube with the 5-α-reductase inhibitor finasteride (daily dose 25mg/kg BW) or were left untreated (controls). Male and female transgenic Gαq (TG, a model of dilative cardiomyopathy) or non-transgenic mice were treated with finasteride for 6 weeks. Results: Cardiac hypertrophy after TAC was dramatically reduced by finasteride in male mice (heart weight/ body weight ratio, HW/BW in mg/g: control 6.65±0.35 versus finasteride treated 5.23±0.3; p&lt;0.01). The reduced hypertrophy in these mice was accompanied by a reduction in cardiomyocyte diameter, ANP expression and fibrosis, but increased capillary density and Serca2a expression. Accordingly, finasteride also markedly reduced hypertrophy in isolated primary rat cardiomyocytes in vitro . Amelioration of hypertrophy by finasteride was associated with blunted activation of the prohypertrophic kinase mTOR in vitro and in vivo . Left ventricular dilation in male Gαq TG mice was markedly reduced by treatment with finasteride, which also led to an improvement in left ventricular function (determined as fractional area change in % by echocardiography: finasteride 44.72±1.71 vs. control 32.8±3.84, p&lt;0.05) and a similar trend was observed in female mice. Interestingly, finasteride reduced pulmonary congestion in male and female mice alike. Conclusion: Finasteride treatment reduces hypertrophy and eccentric cardiac remodelling in mice, indicating a possible involvement of DHT in these processes as well as a potential benefit of 5-α-reductase inhibition in cardiac disease.
Profile of Cell-Derived Microparticles (C-MP) in ITP: Red Cell Microparticles (RMP) Correlate with Severity of ITP.
Authors: Vincenzo Fontana, Pamela Dudkiewicz, Eugene Ahn, Wenche Jy, Lawrence L. Horstman, Myriam Yaniz, Yeon-Soong Ahn
Journal: Blood (2006)
Enhanced Outside-In Signaling Through the Prothrombotic Pro33 Variant of Integrin αIIbβ3 in Adherent Platelets Under Static and Flow Dynamic Conditions
Authors: Marianna Gyenes, Markus Hasse, Volker R. Stoldt, Abdelouahid El-Khattouti, Khon C. Huynh, Rudiger E. Scharf
Journal: Blood (2011)
An Adjustable Markov Model to Project Life Expectancy (LE) for Early Stage Favorable Risk Hodgkin Lymphoma Patients Treated with Contemporary Therapy
Authors: Michael J. Kelly, Susan K Parsons, David C. Hodgson, Joshua T Cohen, Jennifer M Yeh, Jeremy S. Abramson, Debra L. Friedman, Tara O Henderson, Peter W Johnson, Stephen G Pauker, John M. Raemaekers, Jane N. Winter, Kara M. Kelly, Ralph M. Meyer, Sharon M Castellino, Andrew M. Evens
Journal: Blood (2015)
Oral Weekly Cyclophosphamide in Combination with Pomalidomide and Dexamethasone for Relapsed and Refractory Myeloma: Report of the Dose Escalation Cohort
Authors: Rachid Baz, Kenneth H. Shain, Melissa Alsina, Lisa A Nardelli, Taiga Nishihori, Leonel Ochoa, Thomas Martin, Sundar Jagannath, William Dalton, Daniel M Sullivan
Journal: Blood (2012)
Expression of Tissue Factor Is up-Regulated in U937/PR9 Cells by the PML/RARα Fusion Protein through Its Interaction with the Regulatory Region of Tissue Factor Promoter.
Authors: Jingsong Yan, Hongchen Liu, Xiaoyu Su, Ping Wang, Zhen Ruan, Kankan Wang, Zhu Chen, Saijuan Chen, Xiaodong Xi
Journal: Blood (2008)
Prognostic Value of Metabolic Parameters of 18F-FDG PET/CT and Apparent Diffusion Coefficient of MRI in Hepatocellular Carcinoma
Authors: Chae Moon Hong, Byeong-Cheol Ahn, Yun-Jin Jang, Shin Young Jeong, Sang-Woo Lee, Jaetae Lee
Journal: Clinical Nuclear Medicine (2016)

The aim of this study was to predict the survival of patients with hepatocellular carcinoma (HCC) by examining metabolic PET parameters, apparent diffusion coefficients (ADCs), and clinical parameters.We retrospectively reviewed 52 patients with pathologically confirmed HCC (age, 57.9 ± 10.7 years; 43 men) who underwent MRI and F-FDG PET/CT. The tumor-to-normal liver SUV ratio (TLR), the mean ADC of each tumor, and other clinical data were obtained. Survival analysis was performed.Thirty-two patients died during the follow-up period. There was an inverse correlation between the mean SUV and the mean ADC of a tumor (r = -0.402, P = 0.020). Among HCC patients, disease-specific survival was significantly associated with each of the following factors: high TLR (TLR ≥ 2; hazard ratio [HR], 3.78; P = 0.001), high mean ADC (mean ADC ≥ 1.250 × 10 mm/s; HR, 0.45; P = 0.028), AFP ≥ 400 ng/mL (HR, 3.48; P = 0.001), PIVKA-II ≥ 100mAU/mL (HR, 6.39; P = 0.011), tumor size (HR, 1.13; P < 0.001), number of tumors (HR, 2.16; P = 0.031), tumor stage (HR, 3.08; P < 0.001), and surgery for initial treatment (HR, 0.06; P < 0.001). The results of multivariate analysis show that DSS was significantly associated with each of the following factors: TLR ≥ 2 (HR, 2.46; P = 0.044), PIVKA-II ≥ 100mAU/mL (HR, 5.11; P = 0.037), tumor stage (HR, 3.01; P < 0.001), and surgery for initial treatment (HR, 0.04; P < 0.001).High TLRs and low mean ADCs were associated with poor outcomes. The TLR was an independent prognostic factor in patients with HCC, but the mean ADC was not. A negative correlation was found between the mean ADC and the mean SUV of a tumor.
Gene expression analysis of EAC in association with PET response.
Authors: Nicola Wayte, Derek Nancarrow, Euan Thomas Walpole, Guy Lampe, David Gotley, Bernard Mark Smithers, Andrew Barbour
Journal: Journal of Clinical Oncology (2012)

50 Background: Esophagectomy with preoperative chemotherapy or chemoradiotherapy are standard treatment regimens for localized esophageal adenocarcinoma (EAC). Early metabolic response to preoperative therapy (determined by FDG-PET scan) has been shown to predict histological response and survival. We present preliminary data from a randomized phase II trial of pre-operative cisplatin (C), 5-fluorouracil (F) and docetaxel ± radiotherapy based on early response to standard chemotherapy for resectable EAC. We present gene expression data for 22 patients with early FDG-PET response. Methods: Samples that were histologically proven invasive EAC and clinical stage T2/3 tumors were included in the analysis. All patients received C (day1) and F (days 1-4) chemotherapy. Early metabolic response was defined as &gt;35% reduction in SUVmax on day 14 FDG-PET scan compared with baseline scan. Whole genome mRNA expression was obtained for pre-treatment biopsies using HumanHT-12v4 expression chips. Expression data was log2 transformed prior to robust spline normalization conducted with the lumi R package. Statistical analysis was performed in BRBarray. Results: There were 8 early PET responders and 14 early nonresponders to CF chemotherapy. Differentially expressed genes among PET responders and non-responders were identified using a random-variance t-test; 57 genes were identified as significantly differentially expressed between the two classes (p ≤ 0.001). A global test indicated significantly different expression profiles between the classes (p = 0.031). A gene classifier to predict PET response was explored and Support Vector Machines correctly classified 82% of samples with the prediction error estimated using leave-one-out cross-validation (p = 0.05). Epigenetic and apoptotic processes were significantly overrepresented in the gene list based on Gene Ontology analysis. Conclusions: This preliminary work supports a biological basis for the association between early metabolic PET response to preoperative therapy and survival in EAC patients. The list of differentially expressed genes may include potential biomarkers of treatment response and requires further investigation at the maturation of the phase II clinical trial for EAC.
Complete Remissions In 3 of 12 Patients with Pediatric Acute Lymphoblastic Leukemia (ALL) During Phase I Testing of the Anti-CD22 Immunotoxin Moxetumomab Pasudotox
Authors: Alan Wayne, Deepa Bhojwani, Kelly Richards, Maryalice Stetler-Stevenson, Lewis B. Silverman, Sima Jeha, Ching-Hon Pui, Jennifer McDevitt, David J. FitzGerald, Robert J. Kreitman, Robert J. Lechleider, Ira Pastan
Journal: Blood (2010)
HE2100 (5-Androstene-3β,17β-diol) after Cytoreductive Total Body Irradiation of Rhesus Monkeys Promotes the Recovery of Immature CD34+ Bone Marrow Cells, Accelerates Platelet, Granulocyte and Red Cell Reconstitution, and Alleviates Neutropenia and Anemia.
Authors: Fatima S.F. Kaya-Aerts, Trudi P. Visser, Chris L. Reading, James M. Frincke, Monique M.A. Verstegen, Dwight R. Stickney, Gerard Wagemaker
Journal: Blood (2005)
TACI and BCMA, Unlike BAFF-R, Are Expressed by Human Myeloma Cell Lines and TACI+ Cell Lines Have a Gene Signature Indicative of Mature Bone Marrow Plasma Cells and Bone Marrow Environment Dependence.
Authors: Jerome Moreaux, Friedrich W. Cremer, Thierry Reme, Karene Mahtouk, Veronique Pantesco, John de Vos, Marion Moos, Nicolas Robert, Hartmut Goldschmidt, Jean-François Rossi, Dirk Hose, Bernard Klein
Journal: Blood (2005)
C-met as a therapeutic target using ARQ 197 in renal cell carcinoma.
Authors: G. Gibney, P. Conrad, S. A. Aziz, R. L. Camp, B. E. Schwartz, C. Chen, W. K. Kelly, H. M. Kluger
Journal: Journal of Clinical Oncology (2011)

360 Background: c-Met is a receptor tyrosine kinase involved in normal cellular growth and vascular development. It has also been identified as a proto-oncogene. Activating c-Met mutations and indirect c-Met activation via von Hippel-Lindau gene silencing have been demonstrated in renal cell carcinoma (RCC) for papillary and clear cell histologic subtypes, respectively. We studied c-Met expression in a large cohort of RCC tumors and investigated in vitro activity of the new selective c-Met inhibitor, ARQ 197. Methods: Tissue microarrays were performed to analyze c-Met protein expression in situ in 317 RCC tumor specimens using Automated Quantitative Analysis (AQUA). Western blots were performed for c-Met, phospho-c-Met and downstream pathway markers in 6 RCC cell lines (A498, ACHN, Caki-1, Caki-2, 769P, and 786-O). In vitro activity of ARQ 197 was studied by cell viability and clonogenic assays, and by changes in c-Met and down-stream mediators. Results: c-Met expression is higher in RCC than adjacent normal renal tissue (p &lt; 0.0001) and is expressed in all subtypes of RCC, including clear cell carcinoma; expression is highest in papillary and sarcomatoid subtypes. Greater c-Met expression correlates with higher tumor grade (p = 0.0019) and clinical stage (p = 0.0208), and is an independent predictor of poor overall survival (Multivariate Cox LR 5.7, p = 0.017). c-Met expression correlates to decreased survival in the clear cell subset as well. c-Met protein is activated (phosphorylated) in all 6 RCC cells. ARQ 197 inhibits cell growth in RCC cell lines at nanomolar concentrations (IC 50 350-680 nM) and inhibits colony formation at 500 nM. ARQ 197 decreases phosphorylation of c-Met in time- and dose-dependent patterns with dose-dependent decreases in phospho-ERK. Conclusions: c-Met expression is an independent predictor of survival in RCC, including clear cell subtype, suggesting that it is a potential therapeutic target worthy of further investigation. ARQ 197 effectively inhibits proliferation of clear cell carcinoma cell lines. Further preclinical studies are planned to determine mechanism of cellular arrest and apoptosis and markers of drug sensitivity and resistance. [Table: see text]