tbuckley/cabot-search huggingface dataset:
Combination of the Histone Deacetylase Inhibitor Vorinostat with a B-Cell Receptor Signaling Inhibitor Markedly Decreases Cyclin D1 Expression in a Mantle Cell Lymphoma Cell Line
Authors: Kazumi Hagiwara, Hiroatsu Iida, Yasuhiko Miyata, Tomoki Naoe, Hirokazu Nagai
Journal: Blood (2014)
Decitabine Is Effective and Safe In Patients with Chronic Myelomonocytic Leukemia
Authors: Elias Jabbour, Hagop M. Kantarjian, Farhad Ravandi, A. Megan Cornelison, Tapan Kadia, Gautam Borthakur, Jorge E. Cortes, Guillermo Garcia-Manero
Journal: Blood (2010)
Early Deaths (ED) in Acute Promyelocytic Leukemia (APL) in France: A Retrospective Multicenter Study in 355 Patients (pts)
Authors: Rami Rahmé, Xavier Thomas, Christian Recher, Norbert Vey, Jacques Delaunay, Eric Deconinck, Dominique Bordessoule, Jean-Baptiste Micol, Aspasia Stamatoullas, Clara Mariette, Cécile Pautas, Pierre Bories, Jean-Pierre Marolleau, Mathilde Hunault-Berger, Nathalie Fegueux, Emmanuel Raffoux, Hervé Dombret, Sylvie Chevret, Laurent Degos, Pierre Fenaux, Lionel Ades
Journal: Blood (2012)
The use of peptide receptor radionuclide therapy in patients with metastatic low-grade neuroendocrine tumors.
Authors: Boris Naraev, Nancy Sharma, Eric Steven Engelman, David L Bushnell, Thomas M. O'Dorisio, Thorvardur Ragnar Halfdanarson
Journal: Journal of Clinical Oncology (2012)

308 Background: Peptide receptor radionuclide therapy (PRRT) is frequently used for patients (pts) with metastatic low grade neuroendocrine tumors (mNETs) in Europe, but it is not readily available in the USA. We report on 108 patients seen at the University of Iowa who underwent PRRT. Methods: Cases were identified by searching our institutional NET database. Early stage (AJCC 1-3) and high-grade tumors were excluded. Groups were compared using a Wilcoxon rank-sum test and survival calculated with the Kaplan-Meier method. Results: Men were 62% and women 38%; median age at diagnosis was 52 years (25 – 78). The origin of the primary tumor was small bowel (SBNET) 43.5%, pancreas (PNET) 27.8%, lung 4.6%, unknown primary 11.1%, other sites 13%. PRRT was performed at the University of Basel, Switzerland in 72%, University of Iowa, USA in 26%, and elsewhere in 2%. 97 patients received two treatments. 90 Y was used in 86% and 177 Lu in 13% for the first PRRT. The survival of patients is shown in the table 1. Radiographic responses (any) at 1-6 months after PRRT were observed in 62%, 11% had a mixed response and 18% progressed. A biochemical response (&gt;50% reduction) in chromogranin A and pancreastatin was seen in 16% and 19% respectively but data was frequently missing. Conclusions: Patients with mNETs enjoy a relatively long survival. The OS from 1 st PRRT was considerably less than OS after diagnosis, suggesting that PRRT is used late in the disease course. PRRT appears to be a valuable treatment option for mNETs, especially SBNETS, and its role earlier in the disease course warrants investigation. [Table: see text]
Microrna-374b Suppresses Proliferation and Promotes Apoptosis in T-Cell Lymphoblastic Lymphoma By Repressing Wnt-16 and AKT1 and Is a Promising Predictive Biomarker for Patients Survival
Authors: Qingqing Cai, Dong Qian, Kailin Chen, Dan Xie, Huilan Rao, Huiqiang Huang, Xiaofei Sun
Journal: Blood (2014)
Use of early primary tumor response to predict overall survival in patients with metastatic RCC undergoing treatment with sunitinib.
Authors: E. Abel, S. H. Culp, N. M. Tannir, S. F. Matin, P. Tamboli, C. G. Wood
Journal: Journal of Clinical Oncology (2011)

329 Background: In metastatic renal cell carcinoma (mRCC) patients treated with sunitinib and the primary tumor in situ, there is minimal predictive data available to help guide clinicians during treatment with targeted therapy. In prior studies, early primary tumor response (PTR) was associated with improved overall PTR, but the effect on overall survival (OS) is unknown. The purpose of our study was to evaluate whether early PTR was associated with improved OS in mRCC patients undergoing treatment with sunitinib. Methods: We reviewed our institutional database to identify patients with mRCC treated with sunitinib with primary tumor in situ. Clinical and pathological data were collected for each patient. Sequential abdominal CT or MRI scans were reviewed to evaluate PTR. Early PTR was defined as ≥ 10% decrease in tumor diameter within the first 90 days of treatment. Univariable and multivariable stepwise Cox proportional hazards regression analysis were performed to identify predictors of OS in these patients. Results: 75 consecutive patients were identified between 2005 and 2009 with a median follow-up of 15 months. 24 patients exhibited an early PTR; median maximum response 23.1% (range: −53.4, −10.2) and decrease in primary tumor diameter at a median of 90.5 days. Early PTR was associated with a decreased risk of death on multivariate analysis (HR: 0.18; 95% CI 0.05, 0.62, p&lt;0.01). In addition, median OS was improved in patients with an early PTR (30.2 vs. 12.7 months). Independent predictors of decreased survival on multivariate analysis included local symptoms, multiple bone metastases, clinical evidence of venous thrombus, LDH &gt; upper limit of normal, and &gt;2 visceral metastatic sites. Conclusions: Early PTR ≥ 10% is associated with improved survival, better response in metastatic sites, and better overall PTR in patients with mRCC. Future studies should consider this variable when evaluating sunitinib in mRCC treatment. [Table: see text]
Prognostic Assessment of Three Single Nucleotide Polymorphisms (BCL2–938C&amp;gt;A, MTHFR 677C&amp;gt;T, GNAS1 T393C) in Chronic Lymphocytic Leukemia.
Authors: Thorsten Zenz, Ulrich Duehrsen, Harald Dohner, Winfried Siffert, Stephan Stilgenbauer, Holger Nuckel
Journal: Blood (2007)
Safety of abiraterone acetate (AA) in castration-resistant prostate cancer (CRPC) patients with concomitant cardiovascular disease.
Authors: Giuseppe Procopio, Elena Verzoni, Isabella Testa, Davide Biasoni, Tullio Torelli, Nicola Nicolai, Roberto Salvioni, Riccardo Valdagni
Journal: Journal of Clinical Oncology (2012)

168 Background: Abiraterone acetate (AA) is an inhibitor of extragonadal androgen biosynthesis that prolongs overall survival in CRPC patients who have received a chemotherapy including docetaxel. The most common adverse events related to AA therapy were fluid retention, hypertension, hypokaliemia and cardiac disorders. No safety data are available in patients with concomitant cardiac disease. Methods: Metastatic CRPC patients were enrolled in this prospective study if they were also suffering from a concomitant controlled cardiovascular disease. AA 1000 mg per day and prednisone 5 mg bid were administered orally until grade 3-4 adverse events (AE) or disease progression. The primary endpoint was the safety profile while the secondary endpoints were progression-free survival and PSA response. Results: From April to September 2011, 33 CRPC patients with concomitant cardiovascular disorders have been treated with AA. Main patients characteristics were: median age 71 years (range 57–81); baseline mean PSA value 40 ng/ml (6.32-995); the most common sites of disease were bone (27 pts, 81%), lung (11 pts, 33%) and liver (5 pts, 15%). All patients were previously challenged with at least 2 lines of hormone therapy and 1 chemotherapy regimen including docetaxel. The most common pre-existing cardiac disorders were hypertension 22 (66%), arrhythmias 4 (12%), cardiac ischemia 3 (9%) and conduction irregularity 2 (4%). Additionally 9 patients (27%) had metabolic disorders including dislipidemy and hyperglicemia. AA was feasible without inducing grade 3-4 AE nor treatment modification. The most common grade 1-2 AE were asthenia (27%), hypertension (18%) and fluid retention (28%). After a median time of treatment of 4 months (range 2–7 months) no dose modifications due to toxicity were required. No efficacy data are still available. Conclusions: Treatment with AA was feasible and well tolerated also in patients suffering from cardiac comorbidities and risk factors for cardiovascular disease.
Cytogenetic and Molecular Genetic Shifts in 27 Genes Investigated By NGS Depict Specific Routes from MDS to s-AML in 38 Patients with Paired Samples
Authors: Andreia De Albuquerque, Manja Meggendorfer, Wolfgang Kern, Karolina Perglerová, Tamara Alpermann, Claudia Haferlach, Susanne Schnittger, Torsten Haferlach
Journal: Blood (2014)
Germ-line single nucleotide polymorphism (SNP) predictors of progression-free survival and overall survival in patients with advanced prostate cancer treated with androgen-deprivation therapy (ADT).
Authors: M. T. Campbell, J. Jung, S. Philips, Y. Mohammadi, K. A. Carr, T. L. Davis, L. Li, C. Sweeney, T. C. Skaar, N. M. Hahn
Journal: Journal of Clinical Oncology (2011)

51 Background: Significant variation in response duration and overall survival exists among prostate cancer (PCa) patients treated with ADT. Germ-line SNPs affecting function of genes critical to hormone synthesis, transport, metabolism, binding sites, and degradation may contribute to variability in clinical outcomes observed in PCa patients treated with ADT. Methods: Between 1/07 and 10/08, all PCa patients seen in the Indiana University Simon Cancer Center oncology clinics were approached for recruitment to the Prostate Cancer Genetic Risk Evaluation of SNPs Study (PROGRESS). Participants completed a demographic and clinical questionnaire and provided a peripheral blood sample. Only patients with confirmed ADT initiation dates were included in this analysis. Germ-line DNA was analyzed for SNP genotyping on a 128-SNP chip using a TaqMan OpenArray GT Kit (Applied Biosystems). The chip included genes critical to hormone signaling, transport, and elimination pathways with minor allele frequencies &gt; 5%. Patients were followed for progression-free survival (PFS) and overall survival (OS) endpoints. Univariable analyses were performed to identify significant associations between SNP genotype, clinical parameters, and PFS and OS outcomes. Results: 107 patients with PCa initiated on ADT enrolled. Demographics included: age (median)–69 yrs, prostate specific antigen (PSA) (median)–28.0 ng/ml, PSA doubling time (median)–4.9 months, biochemical/metastatic–25%/75%, concurrent anti-androgen therapy–44%. No clinical parameters were associated with PFS and OS. Significant SNP associations with PFS and OS are summarized in the Table. Conclusions: Interpatient differences in hormone pathway germ-line SNPs may contribute to variability in clinical outcomes in patients treated with ADT. [Table: see text] [Table: see text]
Prevalence and clinical characteristics of serum neuronal cell surface antibodies in first-episode psychosis: a case-control study
Authors: Belinda R Lennox, Emma C Palmer-Cooper, Thomas Pollak, Jane Hainsworth, Jacqui Marks, Leslie Jacobson, Bethan Lang, Hannah Fox, Berne Ferry, Linda Scoriels, Hannah Crowley, Peter B Jones, Paul J Harrison, Angela Vincent
Journal: The Lancet Psychiatry (2016)
Expression of p-STAT5, c-MYC and IKZF1 By Immunohistochemistry May Differentially Correlate with Clinical Outcome in Adult B- Lymphoblastic Leukemia (B-ALL) According to BCR-ABL Status
Authors: Bijal D. Shah, Saloomeh Vahdat, Jianguo Tao, Lynn C. Moscinski, Ling Zhang
Journal: Blood (2014)
T-cells targeted with anti-CD3 x anti-HER2 bispecific antibody for treatment of women with stage IV breast cancer (phase I): Clinical and immune function results.
Authors: L. G. Lum, R. Rathore, Z. Al-Kadhimi, P. Davol, A. Thakur, C. Pray, Q. Liu, E. Tomaszewski, F. Cummings, P. Steele, J. Wedge, N. Kouttab, A. Maizel, W. Colaiace, R. Joyrich, V. Ratanatharathorn, J. P. Uberti
Journal: Journal of Clinical Oncology (2011)

2548 Background: Nontoxic immunologic targeting strategies for the treatment of metastatic breast cancer (MBC) are needed. Anti-CD3 activated T cells (ATC) retargeted (armed) with anti-CD3 x anti-Her2 bispecific antibody HER2Bi) exhibit high levels of specific cytotoxicity, proliferate, and secrete cytokines/chemokines. This study was designed to test the safety, survival, persistence, and trafficking of aATC. Methods: We report a phase I trial in 23 patients (pts) with MBC (Her2 0-3+) who received escalating doses of 5, 10, 20, and 40 x 109Her2Bi armed ATC (aATC) twice per week for 4 weeks totaling 40, 80, 160, and 320 x 109 aATC with 300,000 IU/m2/day of IL-2 and GM-CSF 300 µg/m2 twice weekly beginning 3 days before the 1st infusion and ending 1 week after the last infusion. All 7 of the Her2 3+ pts had prior treatment with trastuzumab and most pts had multiple rounds of chemotherapy. Results: Grade III-IV toxicities (NC Immunotherapy Toxicity) by total episodes for 23 pts in decreasing order were chills (60), headache (17), nausea/vomiting (4), backpain (1) hypertension (1), and death (1) due to digoxin toxicity(1). Serum CEA in 3 of 5, CA27-29 in 4 of 4, and Her2 receptors in 4 of 5 pts tested decreased 15-50%. There was 1 partial response 7 months after therapy. Eleven had stable disease and 10 had progressive disease 12-14 weeks after starting aATC in 22 evaluable pts. The median overall survival was 34.5 months for the whole group, 68.8 months for the Her2 3+ group (7 pts), and 25.6 months for the Her 0-2+ group (15 pts). Infusions induced cytotoxicity directed at SK-BR-3 that persisted >4 months, a Th1 cytokine pattern, and increased IL-12p70 levels. aATC circulate for > 96 hrs and biopsies show that aATC localize to tumors. Conclusions: aATC infusions: 1) are safe; 2) induce endogenous cytotoxicity, anti-tumor antibody, and cytokine responses; 3) circulate for >96 hrs; and 4) traffic to tumors. These results suggest that aATC infusions may improve OS by breaking tolerance and “vaccinating” the pts against breast cancer antigens.
Prostate MRI/ultrasound fusion and biopsy yield.
Authors: Daniel Margolis, Dinesh Kumar, Maria Luz Macairan, Ram Narayanan, Shyam Natarajan, Nishant Gandhi, Gregory Shaw, Leonard S. Marks
Journal: Journal of Clinical Oncology (2012)

206 Background: MRI has been shown useful for identifying targets after negative biopsy. We purport to show the advantage of realtime fusion of MRI data with ultrasound for initial or repeat TRUS biopsy compared with sextant biopsy. Methods: An IRB-approved prospective study of 57 consecutive men with diffusion weighted imaging and dynamic contrast enhanced (DCE) perfusion in addition to T2-weighted imaging on a Siemens Magnetom 3.0 T Trio using an external phased array coil had targets chosen based on decreased T2 signal with abnormally restricted diffusion or abnormal DCE by a uroradiologist with 6 years experience in prostate imaging, followed by ultrasound-guided biopsies using MR/ultrasound fusion software (Artemis, Eigen) in addition to standard 12-core sextant biopsies. Results: In 56 patients, 101 suspicious areas were identified by MRI; 28 positive targets were found in 22 men, including 19 Gleason 3+3 (68%), 8 Gleason 3+4 (29%), and one with HGPIN (3%). In 28 patients, neither targets nor systematic cores were positive, and in one patient no targets were identified. Positive cores were found in 12 patients only on targets only including 6 Gleason 3+4. One patient was “upstaged;” the target was Gleason 3+4 whereas the positive systematic cores were Gleason 3+3. In 8 patients the Gleason score of systematic and targeted cores was identical, 2 Gleason 3+4 and 6 Gleason 3+3. In 7 patients systematic cores were Gleason 3+3 with negative targets, all less than 4 mm and less than 25 percent of the core. Fisher exact test showed a trend to significance, p = 0.06 for any cancer identified, and p = 0.03 for Gleason 3+4 disease. Conclusions: The improved accuracy of MRI-TRUS fusion biopsies may be able to replace systematic biopsies, avoiding the discomfort and risks associated, and improve diagnostic yield, and improve confidence for patients with a small amount of low-grade cancer who opt for active surveillance.
Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) after Treatment with Nivolumab for Relapsed/Refractory Hodgkin Lymphoma
Authors: Philippe Armand, Pier Luigi Zinzani, Graham P. Collins, Jonathon B. Cohen, Ahmad S. Halwani, Carmelo Carlo-Stella, Michael M. Millenson, Mariano Provencio, Eva Domingo Domenech, Lisa Giulino Roth, Luca Castagna, Kazunobu Kato, Mihaela Popa McKiver, Anne Sumbul, Lili Zhu, Armando Santoro
Journal: Blood (2016)
Significance of low mTORC1 activity in defining the characteristics of brain tumor stem cells
Authors: Yi-Peng Han, Atsushi Enomoto, Yukihiro Shiraki, Shen-Qi Wang, Xiaoze Wang, Shinya Toyokuni, Naoya Asai, Kaori Ushida, Hosne Ara, Fumiharu Ohka, Toshihiko Wakabayashi, Jie Ma, Atsushi Natsume, Masahide Takahashi
Journal: Neuro-Oncology (2016)

The significance of mammalian target of rapamycin complex 1 (mTORC1) activity in the maintenance of cancer stem cells (CSCs) remains controversial. Previous findings showed that mTORC1 activation depleted the population of leukemia stem cells in leukemia, while maintaining the stemness in pancreatic CSCs. The purpose of this study was to examine the currently unknown role and significance of mTORC1 activity in brain tumor stem cells (BTSCs). Basal mTORC1 activity and its kinetics were investigated in BTSC clones isolated from patients with glioblastoma and their differentiated progenies (DIFFs). The effects of nutrient deprivation and the mTORC1 inhibitors on cell proliferation were compared between the BTSCs and DIFFs. Tissue sections from patients with brain gliomas were examined for expression of BTSC markers and mTORC1 activity by immunohistochemistry. BTSCs presented lower basal mTORC1 activity under each culture condition tested and a more rapid decline of mTORC1 activity after nutrient deprivation than observed in DIFFs. The self-renewal capacity of BTSCs was unaffected by mTORC1 inhibition, whereas it effectively suppressed DIFF proliferation. In agreement, immunohistochemical staining of glioma tissues revealed low mTORC1 activity in tumor cells positive for BTSC markers. In in vitro culture, BTSCs exhibited resistance to the antitumor agent temozolomide. Our findings indicated the importance of low mTORC1 activity in maintaining the undifferentiated state of BTSCs, implicating the relevance of manipulating mTORC1 activity when developing future strategies that target BTSCs.
Breast cancer characteristics in yielders and nonyielders of nipple aspiration fluid.
Authors: V. Brutus, C. McGathey, T. Kmiecik, K. P. Bethke, J. S. Jeruss, N. M. Hansen, S. A. Khan
Journal: Journal of Clinical Oncology (2011)

71 Background: Nipple aspirate fluid (NAF) is an attractive biosample for the investigation of breast cancer risk factors. The reported NAF yield rate varies from 30% to 90% in various studies, raising questions about its value as a risk assessment and about the generalizability of data generated in NAF-yielders to non-yielders. To date, there is no data regarding the characteristics of breast cancers that arise in NAF-yielders and non-yielders. Methods: We examined breast cancer characteristics in NAF yielders and the non NAF yielders in an on-going case control study assessing the hormone concentrations of NAF in breast cancer cases and healthy screening controls. 299 women with recently diagnosed breast cancer were recruited from the Lynn Sage Breast Center. NAF collection was performed from the non cancer breast in the clinic, either before surgery or more than one week post-operatively. NAF yielders produced at least 2 ul of NAF. Each patient completed a detailed study questionnaire. Breast cancer characteristics were recorded on each participant. Results: Among 299 recruited patients 130 (40%) were non NAF yielders (group A) and 169 (60%) were NAF yielders (group B). The association of breast cancer risk factors was compared between them. There were no significant differences in the tumor characteristics. The tumor size, grade, number of positive lymph nodes, and fraction of hormone receptor positive, HER2 positive, and triple negative tumors was similar in NAF-yielders and non-yielders (smallest p value 0.295, for histology, ductal versus lobular). Among the major breast cancer risk factors, the only significant differences were that NAF yielders were younger than non-yielders (50.8 vs. 53.6 years, p &lt; 0.0001) and were more likely to have a history of post-menopausal hormone use (27% among NAF yielders and 7% among non-yielders, p &lt; 0.0001). Conclusions: Tumor characteristics of NAF-yielders and non-yielders are similar, suggesting that there is no qualitative difference between these two groups. The risk predictors developed in yielders can apply to non-yielders.
Population-based analysis of the rising incidence of renal cancer: Evaluation of age-specific trends (1975-2006).
Authors: K. G. Nepple, S. A. Strope
Journal: Journal of Clinical Oncology (2011)

357 Background: Multiple studies show an increasing incidence of renal cancer, possibly related to the rising use of cross sectional imaging. We explored if the increase in renal cancer incidence differs across age groups. Methods: Using the Surveillance, Epidemiology, and End Results (SEER) cancer registry data for the years 1975-2006, we ascertained incident cases of renal cancer. Urothelial histology was excluded. Yearly incidence rates of renal cancer were calculated, age-adjusted to the United States 2,000 standard adult population, and stratified by age group (20-39, 40-49, 50-59, 60-69, 70-79, 80+). Age-specific trends in renal cancer diagnosis over time were evaluated with Poisson regression. Results: 63,843 incident renal cancer cases were identified in 544,684,745 person-years of observation. From 1975 to 2006, overall age-adjusted renal cancer incidence rose 238% from 7.4 to 17.6 per 100,000 adults. The mean age at diagnosis was 61.7 years in 1975, increased to 64.7 years in 1991, and then declined to 62.7 years by 2006. Using 1991 (the year of peak renal cancer age at diagnosis) as the dividing point, the average annual percentage increase in renal cancer incidence was 3.6% from 1976-1990 and 2.9% from 1991- 2006. The age-specific incidence rates of renal cancer increased in all age groups from 1975 to 2006; however the age-specific incidence rates changed at different rates (p&lt;0.0001). Younger age groups showed a more rapid increase in renal cancer incidence over the second half of the study than did the older age groups. For example, for patients age 20-39 years the annual percentage change increased from 4.5% in 1975-1990 to 5.2% in 1991-2006 while annual percentage change decreased from 6.7% in 1975-1990 to 0.9% in 1991-2006 in those over 79 years old. The proportion of patients diagnosed younger than age 65 increased from 45.9% in 1991 to 55.3% in 2006. Conclusions: The incidence of renal cancer has risen steadily since 1975 and continues to increase in all age groups. In the last 15 years, mean age at diagnosis of renal cancer has decreased driven by an increased incidence in younger patients with proportionally less increase in older patients. No significant financial relationships to disclose.