tbuckley/cabot-search huggingface dataset:
Accelerated partial-breast irradiation with the intrabeam intraoperative radiotherapy system.
Authors: R. L. Elliott, M. M. DeLand, J. F. Head
Journal: Journal of Clinical Oncology (2011)

e11569 Background: To evaluate intraoperative accelerated partial breast irradiation (APBI) with the Intrabeam System and access its operation, complications, feasibility, efficacy and cosmesis. The rationale for the evaluation was that local failure after breast conserving surgery (BCS) and total breast radiation usually occurs at the site of the original tumor and therefore delivering radiation directly to the tumor bed should result in better local control. Methods: Starting in 2004, patients over age 50 with invasive ductal carcinoma confirmed by core biopsy were enrolled. Preoperative MRI was used to rule out multifocal disease and ultrasound was used to define margins. Only patients with tumors less than 3.5 cm received intraoperative radiotherapy (IORT). In an effort to achieve adequate surgical margins intraoperative ultrasound was utilized. After resection of the tumor, IORT was delivered to the tumor bed with the Intrabeam System. Results: The procedure has been performed on 94 patients. Eighty-four patients had IORT with the primary surgery, while 10 had IROT during re-exploration of the segmental mastectomy site. Because of final pathology (surgical margins, tumor biology and/or nodal status) 4 patients later had total mastectomy and 18 received total breast irradiation. The IORT serves as the radiation boost when total breast irradiation was done. There have been no serious surgical or radiation complications. Cosmetic results were evaluated by the Harvard criteria and have been good to excellent. To date there have been no local failures. However, the follow-up is not long enough to determine the efficacy of preventing local recurrence. Conclusions: The IORT Intrabeam System is easy to use, versatile, accomplishes excellent cosmesis with few complications, and has great patient acceptance. Further, it is cost effective, and practical for breast APBI in the community setting.
Incidence, Temporal Trends, and Predictors of Thrombocytopenia Among HIV-Infected Persons Treated with Combined Antiretroviral Therapy (cART)
Authors: Michele Bibas, Maria Paola Trotta, Patrizia Lorenzini, Alessandro Cozzi-Lepri, Antonella Castagna, Andrea De Luca, Cristina Mussini, Massimo Puoti, Antonella D’Arminio Monforte, Andrea Antinori
Journal: Blood (2010)
Outcome of Adults with Acute Lymphoblastic Leukemia Treated with a Pediatric-Inspired Therapy: A Single Institution Experience
Authors: Guillermo J. Ruiz-Delgado, Julio Macias-Gallardo, Julia Lutz-Presno, Maryel Montes-Montiel, Guillermo J. Ruiz-Arg\)elles
Journal: Blood (2010)
Protein Expression of p15 and p21 Plays an Unfavorable Prognostic Role in Adult Acute Lymphoblastic Leukemia (ALL) Patients Independently of Their Gene Promoter Methylation Status.
Authors: Fabiana De Cave, Maria Teresa Petrucci, Chiara Gregorj, Maria Rosaria Ricciardi, Samantha Decandia, Paola Bergamo, Sara Santinelli, Antonella Vitale, Giorgina Specchia, Francesco Di Raimondo, Andrea Camera, Eugenio Gallo, Felicetto Ferrara, Francesco Nobile, Nicola Cascavilla, Francesco Fabbiano, Giuseppe Leone, Omar Perbellini, Patrizio Mazza, Luciana Annino, Piero Galieni, Eustachio Miraglia, Giovanna Meloni, Paola Fazi, Marco Vignetti, Robert Foa, Agostino Tafuri
Journal: Blood (2007)
A Human Bone Marrow Failure Syndrome Caused By a Homozygous Mutation in MYSM1
Authors: Ehsan Bahrami, Tomas Racek, Maximilian Witzel, Jacek Puchalka, Naschla Greif-Kohistani, Daniel Kotlarz, Michael Orth, Kirsten Lauber, Christoph Walz, Waleed Al Herz, Hans-Peter Horny, Heinrich Schmidt, Michael H. Albert, Christoph Klein
Journal: Blood (2015)
Early detection of high-grade prostate cancer using digital rectal examination in men with a normal PSA and risk of death.
Authors: Jona Ashok Hattangadi, Ming-Hui Chen, Leon Sun, Anthony Victor D'Amico
Journal: Journal of Clinical Oncology (2012)

147 Background: A digital rectal examination (DRE) is less commonly practiced in the PSA screening era. Whether detection of high-grade prostate cancer (PC) while still clinically localized on DRE can improve survival in men with a normal PSA is unknown. Methods: From the Surveillance, Epidemiology and End Results database, 166,498 men with PC diagnosed between 2004-2008 were identified. Logistic regression was used to identify factors associated with the occurrence of palpable, PSA-occult (PSA &lt;2.5 ng/ml) and Gleason score (GS) 8-10 PC. Factors examined included age at and year of diagnosis and race. Fine and Grays and Cox multivariable regression were performed to analyze whether these factors, treatment and known prognostic factors were associated with the risk of PC-specific mortality (PCSM) and all-cause mortality (ACM), respectively. Results: Of 166,498, 685 men (0.4%) had palpable, PSA-occult and GS 8 to 10 PC. Median age and PSA at diagnosis in this group were 68 years [IQR: 61-75] and 1.5 ng/ml [IQR: 1-2], respectively. Most (83%) men were white. Both increasing age (adjusted odds ratio (AOR): 1.02 [95% confidence interval (CI) 1.01-1.03]; p&lt;0.0001) and white race (AOR: 1.26 [95% CI 1.03-1.54]; p =0.03) were associated with palpable, Gleason 8 to 10 PC with normal PSA. Significant factors associated with an increased risk of PCSM and ACM in this cohort are shown in the table. For these 685 men, detecting locally advanced as compared to localized PC on DRE was associated with a significantly lower survival (p = 0.0001). Conclusions: Detecting PSA-occult high-grade PC with DRE while disease remains clinically localized amongst high-risk men (over age 68 and white race) has the potential to improve survival. [Table: see text]
Early and Delayed 18F-FCH PET/CT Imaging in Parathyroid Adenomas
Authors: Cecilia Vellani, Marina Hodolič, Spyridon Chytiris, Giuseppe Trifirò, Domenico Rubello, Patrick M. Colletti
Journal: Clinical Nuclear Medicine (2016)

Preoperative localization with Tc-sestaMIBI or ultrasound is a common prerequisite for successful minimally invasive parathyroid adenoma (PA) surgery. SPECT/CT with Tc-sestaMIBI and PET/CT with F-FCH offer the possibility of attenuation correction and coregistration of functional and anatomical images providing more accurate PA localization. F-FCH PET/CT is used predominantly in patients with prostate cancer and is under investigation in PA. We report the case of a 43-year-old man with early FCH uptake in a cystic PA with delayed washout at 60 minutes.
PD-1 Is Elevated on the Peripheral Blood T Cell Subsets of Patients with Relapsed/Refractory Hodgkin Lymphoma Compared to Normal Volunteers
Authors: Catherine S. Diefenbach, Rachel Sabado, Sean Clark-Garvey, Crystal Cruz, Isabelita Vengco, Celeste N Rojas, Victoria Serrano, Jasmine M. Zain, Hearn J. Cho, Owen A. O'Connor
Journal: Blood (2011)
Prostate-specific antigen and long-term prediction of prostate cancer incidence and mortality in the general population.
Authors: David D Orsted, Borge G. Nordestgaard, Stig E. Bojesen
Journal: Journal of Clinical Oncology (2012)

5 Background: It is largely unknown whether prostate-specific antigen at first date of testing predicts long-term risk of prostate cancer incidence and mortality in the general population. We tested the hypothesis that baseline prostate-specific antigen levels predict long-term risk of prostate cancer incidence and mortality. Methods: Using a prospective study, we examined 4383 20-94 year old men from the Danish general population followed in the Copenhagen City Heart Study from 1981 through 2009. Prostate-specific antigen was measured in plasma samples obtained in 1981-83. Results: During 28 years of follow-up, 170 men developed prostate cancer and 94 died from prostate cancer. Median follow-up was 18 years (range 0.5-28 years). For prostate cancer incidence, the subhazard ratio was 3.0 (95% confidence interval (CI) 1.9-4.6) for a prostate-specific antigen level of 1.01-2.00 ng/ml, 6.8 (4.2-11) for 2.01-3.00 ng/ml, 6.6 (3.4-13) for 3.01-4.00 ng/ml, 16 (10.4-25) for 4.01-10.00 ng/ml, and 57 (32-104) for &gt;10.00 ng/ml versus 0.01-1.00 ng/ml.. For prostate cancer mortality, corresponding subhazard ratios were 2.2 (1.3-3.9), 5.1 (2.8-9.0), 4.2 (1.8-10), 7.0 (3.8-14), and 14 (6.0-32). For men with prostate-specific antigen levels of 0.01-1.00 ng/ml, absolute 10-year risk of prostate cancer was 0.6% for age &lt;45 years, 0.7% for 45-49 years, 1.1% for 50-54 years, 1.2% for 55-59 years, 1.3% for 60-64 years, 1.1% for 65-69 years, 1.3% for 70-74 years, and 1.5% for age≥75 years; corresponding values for prostate-specific antigen levels &gt;10.00 ng/ml were 35%, 41%, 63%, 71%, 77%, 69%, 75%, and 88%, respectively. Conclusions: Stepwise increases in prostate-specific antigen at first date of testing predicted a 3-57 fold increased risk of prostate cancer, a 2-16 fold increased risk of prostate cancer mortality, and a 35-88% absolute 10-year risk of prostate cancer in those with prostate-specific antigen levels &gt;10.00 ng/ml. Equally important, absolute 10-year risk of prostate cancer in those with levels 0.01-1.00 ng/ml was only 0.6-1.5%.
Proximity-Based Single Cell Analysis of the Bone Marrow Niche Identifies Interleukin-18 As a Quiescence Regulator of Early Hematopoietic Progenitors
Authors: Lev Silberstein, Peter Kharchenko, Youmna Kfoury, Francois Mercier, Masatake Osawa, Jonathan Hoggatt, Tiffany Tate, Charles Lin, David T. Scadden
Journal: Blood (2014)
Identification of potential molecular candidate lesions by molecular analysis of desmoid tumors with qrt-PCR and high-density SNP arrays.
Authors: P. Erben, D. Nowak, W. Hofmann, R. Hofheinz, P. Hohenberger, B. Kasper
Journal: Journal of Clinical Oncology (2011)

10081 Background: Aggressive fibromatoses (AF; desmoid tumors) are clonal, neoplastic proliferations of connective tissues. Tyrosine kinase inhibitors (TKIs) such as imatinib can be effective in controlling disease (Mace, Cancer, 2002). However little is known about the molecular mechanisms of tumorigenesis, risk of relapse and sensitivity against TKIs. Therefore we carried out a molecular analysis with quantitative reverse transcriptase PCR (QRT- PCR) and high density SNP array analysis, in order to possibly elucidate new molecular mechanisms underlying these tumors. Methods: The study included 11 patients with AF (8 females, 3 males; median age 33.5). Patient’s treatment included surgery (n = 11), radiotherapy (n = 6), antihormonal/anti-inflammatory treatment (n = 2), chemotherapy (n = 3) and imatinib therapy (n = 2). Total RNA and genomic DNA were extracted from the resected specimen for molecular analysis. A QRT-PCR assay was used for expression analysis of PDGFRA, PDGFRB and c-KIT. High resolution copy number analysis was carried out with 8 samples using Genome-Wide Human SNP 6.0 arrays (Affymetrix, Santa Clara, CA,USA). Results: The comparison of PDGFRA, PDGFRB and C-KIT ratios in normal tissues vs. desmoids tumor tissues showed no significantly higher ratios in the tumor samples. High density SNP array analysis revealed several genomic lesions: In single samples numerical aberrations were found on chromosome (chr.) 20 and 6 with either trisomy 20 and monosomy 6 or heterozygous deletions of chr. 5q (including the APC gene), chr. 13q and chr. 10p. Putative sub-microscopic duplications were discovered on chr. 17q, 7p and 8p. These contained the coding regions for human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR) and runt-related transcription factor 1 gene (RUNX1T1) as possible new candidate genes in the molecular biology of AF. Conclusions: We describe a comprehensive genomic profilingof tumor DNA in AF. Thereby genomic alterations point to candidate genes,which could be factors in addition to known aberrations.Therefore, our data helps to provide a better understandingof the molecular mechanisms underlying the development of AF.
Tissue expression of Uridine and Thymidine phosphorylases and NF-κB in breast cancer patients by tissue microarray
Authors: Mary McCarthy, Laxiang Wan, Amy Ziemba, Harriet Kluger, Giuseppe Pizzorno
Journal: Cancer Research (2007)

4565   Uridine phosphorylase (UPase) and thymidine phosphorylase (TPase) are both upregulated in various human solid tumors and catalyze the reversible phosphorolysis of deoxynucleosides and a wide variety of fluorinated pyrimidine nucleosides. The relative contribution of each of these enzymes varies among different tumor tissues.  Uridine phosphorylase activity, in particular, has been reported to be elevated in many tumors, including breast cancers, colorectal cancer, oral squamous carcinomas, melanomas, and lung adenocarcinomas, when compared with adjacent normal tissues. In these studies on small cohorts of patients, the overexpression of UPase was associated with worse long-term survival. Our recent studies have indicated that the NF-κB p65 transcription factor activates UPase expression via sequence-specific binding to the UPase promoter enhancing the sensitivity of murine breast cancer cells (EMT-6) to fluoropyrimidine antimetabolites. We have shown that some cis-acting elements including NF-κB, IFN-regulatory factor-1 (IRF-1) and STAT-1 in the UPase promoter play a critical role in the induction of UPase in combination with TNF-α and IFN-γ. Also, in a small study on fresh frozen human breast cancer specimens, employing Western blot and enzymatic assays, we observed that the UPase activity was higher in the breast cancer tissues and NF-kB p65 expression was associated with the increased UPase activity.  >We evaluated the association between UPase, TPase and NF-kB expression and clinical variables on tissue microarrays containing primary specimens from 655 breast cancer patients using a method of automated quantitative analysis (AQUA). Nuclear and cytoplasmic expression of NF-kB was associated with a high nuclear grade (>1/3) (P=0.0070 and P=0.0004, respectively). UPase and TPase expression are associated with tumor size; high expression was seen in tumors >2 cm (P=0.0065 and P=0.0332, respectively). We also observed a direct correlation between UPase and TPase expression (P=0.0004). High TPase expression was associated with decreased survival in the node-positive patient subset by Kaplan-Meier survival analysis (P=0.0478). No association was seen between expression of NF-kB and either phosphorylase.  >Given the role of both phosphorylases in the activation and selectivity of fluoropyrimidine antimetabolites, we are in the process of evaluating the association between response to therapy with 5-FU based therapy in early stage breast cancer patients.
Phase I study of at-101 (R-(-)-gossypol) in combination with paclitaxel (P) and carboplatin (C) in solid tumors including castrate-resistant prostate cancer (CRPC).
Authors: Y. Zhao, M. Gounder, H. Lin, K. Harris Addo, K. Taber Levinson, M. LaRosiliere, S. Goodin, R. A. Moss, A. R. Tan, M. N. Stein
Journal: Journal of Clinical Oncology (2011)

169 Background: The combination of paclitaxel (P) and carboplatin (C) has broad anti-tumor activity in multiple tumor types including prostate and bladder cancer. Overexpression of Bcl-2 is a common mechanism of resistance to cytotoxic chemotherapy. AT-101 is an oral inhibitor of Bcl- 2-family-anti-apoptotic proteins. We conducted a phase I study of the combination of AT-101, P and C. Methods: Ph I study in pts with refractory solid tumors, ECOG 0-1, using a standard 3+3 design to evaluate safety, tolerability and pharmacokinetics/pharmacodynamics (PK/PD). AT-101 was administered orally on Days 1-3 Q12 hr. P and C were administered intravenously on day 1 every 21 days. Dosing levels (DL) were 1: AT-101 40 mg BID, P 150mg/m 2 , C AUC 5; and DL 2: AT-101 40 mg BID, P 175/m 2 , C AUC 6. 12 additional pts treated at the MTD dose level were divided into two groups – with AT-101 omitted in the morning of C1D1 or C2D1 to assess apoptotic markers during P and C chemotherapy with and without AT-101. Results: 24 pts (CRPC-11, colon-3, breast-3 melanoma-2, penile-1, esophageal adeno-1, thymus adeno-1, bladder neuroendocrine-1, NSCLC-1) with median age of 61.5 were enrolled. 6 pts were treated in DL1, and 18 in DL2 (the MTD). Dose limiting toxicities were G3 abdominal pain (1 pt, DL1) and G3 ALT (1pt, DL2). Common G1/G2 AEs were nausea, vomiting, fatigue, anorexia and neutropenia. 4 pts had dose reductions after cycle 1 due to AEs. 12 pts had GCSF added after C1 due to neutropenia. 4/11 (36%) pts with CRPC (all previously treated with docetaxel) had PSA declines of ≥50% and 4 pts had stable disease from 4 to 14 cycles. 2 pts with CRPC had a PR by RECIST. Additionally, 1 pt with esophageal CA had a CR and 1 pt with NSCLC had a PR. PK analysis demonstrated P PK was not influenced by co- administration of C and AT-101 when compared with historical reports (Siddiqui BJC 1997). The PK of AT-101 was not altered significantly by the P dose levels. Conclusions: The addition of AT-101 to PC chemotherapy is well tolerated and clinically active in advanced cancer pts. The combination of AT-101 and PC may be appropriate for further study in pts with chemorefractory CRPC. No significant financial relationships to disclose.
Use of patient navigation to improve diagnostic and treatment delays among patients with abnormal mammography results from a mobile unit.
Authors: J. Y. Lee, R. S. Henry-Tillman, V. S. Klimberg, R. Fincher, K. Enoch, M. Preston, S. Jackson, P. Kenney
Journal: Journal of Clinical Oncology (2011)

73 Background: Screening mammography is frequently the initial step to breast cancer diagnosis. Upon detection of an abnormality on a mammogram, the patient must undergo follow-up procedures for diagnosis and treatment. The objective of this study was to examine the diagnostic and treatment delays after detection of an abnormality on a mammogram performed at a mobile unit. Methods: During one-year beginning in February 2010, the mobile mammography unit of the University of Arkansas for Medical Sciences (UAMS) performed 1,547 mammograms in women who resided in counties that lacked a stationary mammography unit. Most of these counties are in rural areas with high poverty rates. The women were predominantly non-Hispanic white (62%) or African-American (36%) and 41% lacked health insurance. A patient navigator was available to assist patients through scheduling follow-up appointments, when needed. Diagnostic delay was defined as time from abnormal mammogram to biopsy that exceeded 60 days. Treatment delay was defined as time from abnormal mammogram to treatment initiation that exceeded 90 days. Results: A total of 14 cancer cases were detected among the 1,547 women screened. The median age of these patients was 56 years of age and ranged from 46-79 years. The median time from screening mammography to biopsy was 31.5 days and ranged from 9-92 days, and diagnostic delay occurred in 2 (14%) patients. The median time from screening mammography to treatment was 78 days and ranged from 37-199 days, and treatment delay occurred in 5 (36%) patients. Three of these patients were managed outside the UAMS health care system, one patient required bilateral mastectomies and one patient refused the initial treatment recommendation. Conclusions: Responsive health systems require vehicles to strengthen the continuum of breast care. With the use of a patient navigator, the proportion of patients with breast cancer who experienced diagnostic delays is comparable to that of other studies, but the proportion with treatment delays is higher than in other reports. Patient navigation provides a promising model to decrease diagnostic delays and improve access for the medically underserved.
Biological and Clinical Relevance of Associated Genomic Alterations in MYD88 L265P and non-L265P–Mutated Diffuse Large B-Cell Lymphoma: Analysis of 361 Cases
Authors: Sydney Dubois, Pierre-Julien Viailly, Elodie Bohers, Philippe Bertrand, Philippe Ruminy, Vinciane Marchand, Catherine Maingonnat, Sylvain Mareschal, Jean-Michel Picquenot, Dominique Penther, Jean-Philippe Jais, Bruno Tesson, Pauline Peyrouze, Martin Figeac, Fabienne Desmots, Thierry Fest, Corinne Haioun, Thierry Lamy, Christiane Copie-Bergman, Bettina Fabiani, Richard Delarue, Frédéric Peyrade, Marc André, Nicolas Ketterer, Karen Leroy, Gilles Salles, Thierry J. Molina, Hervé Tilly, Fabrice Jardin
Journal: Clinical Cancer Research (2016)

Purpose:MYD88 mutations, notably the recurrent gain-of-function L265P variant, are a distinguishing feature of activated B-cell like (ABC) diffuse large B-cell lymphoma (DLBCL), leading to constitutive NFκB pathway activation. The aim of this study was to examine the distinct genomic profiles of MYD88-mutant DLBCL, notably according to the presence of the L265P or other non-L265P MYD88 variants.Experimental Design: A cohort of 361 DLBCL cases (94 MYD88 mutant and 267 MYD88 wild-type) was submitted to next-generation sequencing (NGS) focusing on 34 genes to analyze associated mutations and copy number variations, as well as gene expression profiling, and clinical and prognostic analyses.Results: Importantly, we highlighted different genomic profiles for MYD88 L265P and MYD88 non-L265P-mutant DLBCL, shedding light on their divergent backgrounds. Clustering analysis also segregated subgroups according to associated genetic alterations among patients with the same MYD88 mutation. We showed that associated CD79B and MYD88 L265P mutations act synergistically to increase NFκB pathway activation, although the majority of MYD88 L265P-mutant cases harbors downstream NFκB alterations, which can predict BTK inhibitor resistance. Finally, although the MYD88 L265P variant was not an independent prognostic factor in ABC DLBCL, associated CD79B mutations significantly improved the survival of MYD88 L265P-mutant ABC DLBCL in our cohort.Conclusions: This study highlights the relative heterogeneity of MYD88-mutant DLBCL, adding to the field's knowledge of the theranostic importance of MYD88 mutations, but also of associated alterations, emphasizing the usefulness of genomic profiling to best stratify patients for targeted therapy. Clin Cancer Res; 23(9); 2232-44. ©2016 AACR.
Deletion of Bcl11a Gene Reveals Roles in Lymphoid, Myeloid, and Leukemic Cell Development.
Authors: Mariaestela Ortiz, P. Liu, L. Tessarollo, R.A. Rachel, T. Nakamura, Steven W. Stull, N.A. Jenkins, N.G. Copeland, J. R. Keller
Journal: Blood (2004)
Phase 1b Study of Otlertuzumab (TRU-016), an Anti-CD37 ADAPTIRTM Protein, in Combination with Rituximab in Patients with Chronic Lymphocytic Leukemia (CLL)
Authors: Kami J. Maddocks, John Pagel, John C. Byrd, Scott Stromatt, Farrukh Awan
Journal: Blood (2014)
Cytotoxic T-Cell Response to the Cancer Testis Antigen PASD1 In Multiple Myeloma: PASD1 Peptides for a Generic Vaccine to Treat PASD1-Positive Haematological Malignancies
Authors: Andrew J Campbell, Kamel Ait-Tahar, Suketu D. Patel, Martin Barnardo, Amanda P Liggins, Maite Caibes, Alison Banham, Graham Collins, Chris S.R Hatton, Karen Pulford
Journal: Blood (2010)
Longterm Outcome of Induction Chemotherapy of P-Gemox Regimen Followed By Extensive Involved-Field Radiotherapy(EIFRT) for Newly Diagnosed Stage I/II Extranodal Natural Killer/T-Cell Lymphoma---a Single Center Experience
Authors: Huiqiang Huang, Yan Gao, XiaoXiao Wang, Qingqing Cai, QiChun Cai, Bing Bai, Zheng Yan, Wenqi Jiang, Zhongjun Xia, ZhiMing Li
Journal: Blood (2015)