tbuckley/cabot-search huggingface dataset:
Use of variation in sex steroid methyl transferases to predict efficacy of androgen-deprivation therapy (ADT) in advanced prostate cancer.
Authors: M. Kohli, D. W. Mahoney, H. S. Chai, D. W. Hillman, D. R. Rider, B. A. Costello, J. R. Cerhan
Journal: Journal of Clinical Oncology (2011)

14 Background: We evaluated the association of germline variation in genes regulating hormonal pathways with duration of treatment response in prostate cancer patients receiving ADT, focusing on genes in the androgen biosynthesis (the C4 Δ; C5 Δ; C21 CYP pathways and the alternate “backdoor pathway”) and metabolism pathways. Methods: We successfully genotyped 747 single nucleotide polymorphisms (SNPs) from 84 genes in a cohort of 304 patients with advanced prostate cancer who progressed on ADT. Tagging SNPs with a minor allele frequency (MAF) of &gt;5% and r 2 ≥0.8 were selected from HapMap, NIEHS and Seattle SNP databases. The primary endpoint was time to ADT failure, and we conducted a gene-level test (principal components), along with individual SNP level tests adjusted for patient age and Gleason score. To account for multiple testing, we calculated the false discovery rate (FDR), and FDRs of 0.10 were considered noteworthy. Results: The median age of the cohort at ADT failure was 72 years (range 65-78 years), and the overall median time to ADT failure was 3.21 years (IQ [25-75]: 1.54-6.20 years). At the gene level, TRMT11 (tRNA methyltransferase 11 homologue) showed the strongest association with time to ADT failure (p&lt;0.0008; adjusted p-value for FDR-0.068). Two of four TRMT11 tag SNPs were associated with time to ADT failure. The first was the intronic SNP rs1268121 (A&gt;G) with a MAF of 15%, for which there was a positive association of median time to ADT failure with the number of variant alleles (p=0.023): 3.1 years for 0, 4.1 years for 1, and 5.9 years for 2 variant alleles. The second was the SNP rs6900796 (A&gt;G) in the 3' untranscribed region with a MAF of 49%, for which the median time to ADT failure was 2.6 years for 0, 2.5 years for 1, and 3.8 years for 2 variant alleles (p=0.023). Four additional genes showed an association with ADT response at the p&lt;0.10 level, including LOC390956, PRMT3, SLC7A6OS, and WBSCR22, although all FDRs were &gt;0.95. Conclusions: Variation in TRMT11 was associated with time to ADT failure. Confirmation of these findings in an independent cohort is needed. No significant financial relationships to disclose.
Spliceosomal Targeting in Acute Myeloid Leukemia Cells with ETV6-NTRK3 Fusion.
Authors: Suning Chen, Bjoern Schneider, Stefan Nagel, Robert Geffers, Maren Kaufmann, Hilmar Quentmeier, Hans G. Drexler, Roderick A.F. MacLeod
Journal: Blood (2009)
Serum Lactic Acid (LA) as a Predictor of Septic Shock in Patients with Hematologic Malignancies (HM) Who Develop Febrile Neutropenia
Authors: Anthony R Mato, Selina Luger, Alison W. Loren, Daniel F Heitjan, Erin R. Olson, Chaitra S Ujjani, Samantha Jacobs, Payal D. Shah, Andrea N. Miltiades, David Wang, Kevin Lux, Elise Chong, Laura L Belby, Donald E. Tsai, Barry D. Fuchs
Journal: Blood (2008)
Use of metabolomic profiling to identify potential markers and mechanism for bladder cancer progression.
Authors: N. Putluri, V. T. Vasu, A. Shojaie, G. S. Thangjam, S. Vareed, C. T. Tallman, V. Putluri, C. Butler, J. G. Giri, T. R. Sana
Journal: Journal of Clinical Oncology (2011)

250 Background: Bladder cancer (BCa) is the second most prevalent urological malignancy and the fourth highest cause of cancer-related death in the United States that is known to be caused by defects in xenobiotic metabolism, which is not well understood. Using unbiased mass spectrometry we report the metabolomic profiles in BCa tissues and demonstrate its biomarker potential as well reveal a possible mechanism regulating altered xenobiotic metabolism in these tumors. Methods: Total metabolome from clinically annotated bladder-derived tissues were examined using mass spectrometry coupled to reverse and aqueous normal phase separation of compounds. Class- specific metabolites were examined in urine specimens for their biomarker potential as well as analyzed using Oncomine Concept Map for alterations in bioprocesses. The latter was validated using a collection of molecular techniques like Q-PCR, immunoblot analysis, methylation assays and use of methyl transferase inhibitor, on bladder-derived cell lines and patients specimens. Results: A total of 2,019 compounds were detected across the 58 bladder-derived specimens, of which 50 named compounds were differential between BCa and its adjacent benign tissue. These included aromatic compounds like aniline, catechols as well as polyamines and S-adenosyl methionine (SAM). A subset of these compounds, were detected in urine and could distinguish BCa from benign, non-muscle-invasive from muscle invasive tumors and delineate patients responding to chemotherapy and TURBT. Bioprocess mapping of BCa-specific metabolome revealed co-enriched concepts describing methylation and cytochrome P450 (CYP) driven xenobiotic metabolism in bladder tumors. The role of methylation in regulation of CYP activity in BCa was confirmed using a combination of Aza-treatment, methylation-specific PCR and bisulphite sequencing on bladder-derived cell lines and tissues. Conclusions: Unbiased metabolomic profiling reveals potential non-invasive metabolic markers for early detection, prognosis and therapeutic response of BCa as well as describes a role for methylation induced silencing of CYP1A1 and 1B1resulting in deficient xenobiotic metabolism in BCa. No significant financial relationships to disclose.
Outcome of 157 adult rhabdomyosarcoma (RMS) patients: A retrospective study from the French Group Sarcoma (GSF-GETO).
Authors: E. Bompas, L. Campion, A. Italiano, A. l. Cesne, M. Giaj Levra, C. Chevreau, S. Piperno-Neumann, N. Isambert, A. Thyss, M. Rios, J. Kurtz, C. Delcambre, J. Bay, F. Duffaud, M. Trassard, P. Soulie, J. Blay
Journal: Journal of Clinical Oncology (2011)

10070 Background: Five-year overall survival (OS) of localized RMS of children < 18 exceeds 70%, while OS in adult pts is poor. We report a retrospective experience from centers of GSF-GETO. Methods: From May 1981 to February 2010,157 adult pts (≥18 yrs) treated in 13 centers were analyzed. OS was determined using Kaplan-Meier method and analyzed with the logrank test and Cox model. Results: At diagnosis, 111 pts had localized RMS without lymph nodes (N) and/or (+/-) metastases (M). There were 100 males and 57 females (median age: 37 yrs, range 18-86). Histologic subtypes were embryonal (E) (21%), alveolar (A) (35%) and pleomorphic (P) (44%). Primary tumor site were limbs (48%), head and neck (25%), genitourinary (9%) and others (18%). Median tumor size was 8 cm (range 1-56). E, A, and P RMS were located in the limbs (18% vs 33% vs 75% p=0.001), with a median age of 25 vs 26 vs 51 yrs respectively (p=0.001) and N +/- M (21% vs 53% vs 14% p=0.001). 125 pts received chemotherapy (CT) including 81/111 with localized RMS. RMS subtype influenced clinical management, adjuvant CT (58% for P and 92% for E/A RMS), administration of pediatric protocols (PP) (14% for P and 62% for E/A RMS) (p<0.001). Surgery was performed in 108/157 (69%) pts with R0, R1 or R2 margins in 60%, 28% and 10% respectively among 96 evaluable pts. 107 pts (81 with localized RMS) received radiotherapy (RT). With a median follow up of 8.5 yrs, 5-yrs OS for localized RMS and advanced RMS were 43% and 5% (p<0.0001) and 52%, 20%, 46% for E, A and P localized RMS respectively (p=0,2). In multivariate analysis, for localized RMS, A RMS (p<0.001), age (p=0.001), sex (male) (p=0,045), R0 resection (p<0.001), RT (p<0.001) and PP (p=0,002) influenced OS. For RMS with N +/- M, age (p=0,062), sex (p=0.068), R0 resection (p=0.015), RT (p=0.085) influenced OS. Conclusions: Outcome of pts remains poor for all subtype RMS, E/A RMS compared to childhood RMS and P RMS compared to STS in adult pts.Surgery allows better outcome for all patients. Respect of PP for localized RMS should be preferred.
HMGA2 Dysregulation in Myelofibrosis with Myeloïd Metaplasia (MMM) Versus Other Phi-Negative Chronic Myeloproliferative Disorders and Myelodysplasia.
Authors: Chrystèle Bilhou-Nabera, Joris R. Andrieux, Olivier Pierre-Louis, Marie-Caroline Le Bousse-Kerdilès, Brigitte Dupriez, Nathalie Grardel, Agnès Charpentier, Vincent Praloran, Francis Bauters, Jean Luc Laï, Jean Loup Demory
Journal: Blood (2004)
A novel xenograft model of gastrointestinal stromal tumors.
Authors: Jason Keith Sicklick, Stephanie Yvette Leonard, Evangeline Mose, Randall P French, Michele Criscuoli, Dawn V Jaquish, Karly Maruyama, Richard B. Schwab, David Cheresh, Andrew M. Lowy
Journal: Journal of Clinical Oncology (2012)

202 Background: GIST treatment with imatinib has served as the prototype for targeted molecular therapy. However, patients frequently acquire drug resistance to imatinib and this has prompted the development of additional multi-kinase inhibitors. To date, preclinical testing of novel agents has predominantly been performed using cell line based subcutaneous xenografts that may overestimate drug activity in the clinic. This suggests that novel in vivo models are needed to improve prediction of clinical efficacy. We hypothesized that human GISTs could be intra-peritoneally xenografted into immunodeficient mice in order to better recapitulate the microenvironment and biology of GIST. Methods: Tumor acquisition was performed under an IRB-approved protocol. Following tumor resection, we anesthetized NOD-scid (NS) or NS gamma (NSG) mice and performed a midline laparotomy. 2′2 mm tumor fragments were sutured into the abdominal viscera of NS (N=10) or NSG (N=15) mice. Tumors were imaged every 3-4 wks with ultrasound (US). 2 mice were also evaluated with PET scan. Results: We have xenografted GISTs from 3 patients into 25 mice with an 80% success rate and 4% perioperative mortality. We observed tumor progression in the liver (9/10), renal capsule (8/10), lesser sac (2/3), or gastric wall (1/2) of mice. This included 14 primary xenografts and 11 passaged xenografts. At 21-196 d (median 46 d), tumor size averaged 473±736 mm 3 (median 104 mm 3 , range 2.2-2683 mm 3 ) by US. In addition, 30% (6/20) of mice developed metastatic disease based upon US, necropsy, histology and/or KIT immunostaining. We also determined that 2/2 tumors were FDG-avid on PET. Conclusions: To our knowledge, we report the first intra-peritoneal xenograft model of human GIST using patient-derived tumor tissue. This novel in vivo approach is a reproducible model of human GIST that replicates the tumor microenvironment, heterogeneity, and metastatic potential of a human GI sarcoma. As compared to current research tools/models, this approach may allow researchers to better predict chemotherapeutic responses, further understand the tumor biology of GIST, and serve as a means to propagate additional tumor tissue for subsequent experimental analyses.
Clinical outcome of triple-negative breast cancer with BRCA mutation in the context of dose-dense and or metronomic chemotherapy.
Authors: R. S. Mehta, C. Liu
Journal: Journal of Clinical Oncology (2011)

1109 Background: Patients with triple negative (TN) breast cancer have a high risk of early relapse and death, but have promising outcomes with dose-dense and or metronomic combination chemotherapy in BRCA-unselected cohort (rsmehta JCO 2008). With the TN breast cancer, emerging data suggests that patients with BRCA mutations treated with chemotherapy have similar outcomes as sporadic TN breast cancer. Methods: Retrospective review of 88 patients with stage I to IIIB TN breast cancer who were treated with adjuvant or neoadjuvant chemotherapy was performed. Fifteen patients (18%) were found to have BRCA mutation (12 with BRCA1 and 3 with BRCA2 mutation) while 69 patients were either negative for BRCA mutation or were not tested. Patients were treated with various regimens, but could be grouped according to the receipt of dose-dense and or metronomic (DD) versus standard (Std) chemotherapy schedules. The median follow-up was 41 months (range 4-155 months). Results: Grade, histology and stage were not significantly different between carriers and noncarriers. Mean age of carriers was 39 versus 50 for noncarriers. Relapse-free-survival survival at 3 years was 100% for carriers and 70% for noncarriers (P =0.15). Overall survival at 3 years was 100% for carriers and 83% for noncarriers (P = <0.05). In addition, stage and treatment (DD vs Std) were significant in univariate analysis. Adjusting for carrier status, stage, and treatment, only stage and treatment remained significant for relapse-free and overall survival. Conclusions: Our data supports the emerging data that shows that BRCA mutation carriers with TN disease had similar survival rates to noncarriers. Dose-dense and or metronomic schedules outperformed standard chemotherapy schedules in TN breast cancer irrespective of BRCA mutation status.
Close or positive margins after mastectomy in early-stage, node-negative breast cancer: The association of tumor grade with local recurrence.
Authors: J. R. Hastings, S. Iganej, D. M. Bugoci, C. Huang
Journal: Journal of Clinical Oncology (2011)

1045 Background: Mastectomy for early-stage, node-negative breast cancer results in high rates of disease control. However, radiation oncologists are often consulted regarding close or positive margins. We retrospectively evaluated factors related to local relapse (LR) among this cohort. Methods: 2542 women underwent mastectomy for pT1N0 breast cancer from 1994-2004 within Southern California Kaiser Permanente. The study group consists of 230 of these patients who had an invasive or in-situ margin <10 mm and did not receive chest wall radiotherapy. Median age was 63. Median tumor size was 1.3 cm, with a median of 10 lymph nodes dissected. Grade 3 was present in 26%, and lymphovascular invasion (LVI) in 13%. Hormone receptor positivity was 73%. Adjuvant chemotherapy (primarily CMF) was given to 33%, and hormonal therapy was prescribed to 63%. The median closest margin was 4 mm, and 21% of patients had margins < 2 mm. Risk factors analyzed were age (≤50 vs >50), tumor size, grade (3 vs 1−2), LVI, hormone receptor status, type of mastectomy (modified radical vs other), fascia removal, closest margin, number of lymph nodes dissected, and receipt of adjuvant systemic therapy. Kaplan-Meier survival curves were compared with the log-rank test. Results: At a median follow-up of 6.52 years, the overall survival was 82.1%, distant-metastasis-free survival 95%, and local-relapse-free survival (LRFS) 96.3%. Median time to LR was 1.4 yrs. Chest wall was the only site of LR; only 1 patient with LR went on to develop distant metastasis. Grade 3 and margin < 2 mm were significantly associated with LR. LRFS was 88.1% for grade 3 vs 98.6% for grade 1−2 (p = 0.017), and 89.2% for margins < 2 mm vs 98.2% for margins of 2−10 mm (p = 0.026). Among 13 patients who had both grade 3 and a margin < 2 mm, 3 developed LR, as compared to only 1 LR in 125 patients with neither factor (p = 0.002). Conclusions: This review suggests that in patients undergoing mastectomy for pT1N0 breast cancer, high-grade disease in the setting of a close or positive margin is associated with an increased risk of chest wall relapse, and may be an indication for post-mastectomy radiotherapy.
Clinical characteristics of triple-negative breast cancer.
Authors: M. H. Hur, R. J. Im, S. Lee, C. S. Yoon, S. S. Ko, H. Lee, J. Y. Kim, J. H. Lee, S. S. Kang
Journal: Journal of Clinical Oncology (2011)

e11565 Background: Breast cancer represent a heterogenous group of tumors that are diverse in behavior, outcome, and response to therapy. To reduce mortality from breast cancer, there is a desire to examine and characterize tumors of poor prognosis, to predict their biology, to ensure adequate therapy. In this study, we investigate the clinical characteristics of triple negative breast cancer (ER, PR, c-erb B2 negative, immunohistochemically: TN tumors) that lacks the benefit of targeted therapy. Methods: From January 1995 to December 2002, 1,325 invasive breast cancer patients were operated. We investigated them retrospectively, who had the median follow-up for 62 months. We examined the differences between triple negative breast cancer compared with Non-triple negative breast cancers in relation to the clinicopathologic parameters, overall survival (OS), disease free survival (DFS). Statistical analysis was performed using SPSS (Chi-square, logistic regression, Kaplan-Meier) Results: 213 (16.1%) cases among 1,325 patients were triple negative breast cancers. There were positive associations with younger age (below 35 years), poorly differentiated nuclear grade, negative axillary lymph nodes in TN tumors. Tumor size, histologic classifications, lymphovascular invasion were not significantly different between TN tumors and the other group. 199 patients (93.4%) were treated with chemotherapy. 26 cases (12.2%) of TN tumor experienced locoregional or systemic metastases, and 20 cases (9.4%) died. There was no significant difference of 5 year OS and DFS between TN tumors and the other group. Conclusions: Triple negative breast cancers are associated with poorly differentiated nuclear grade and affect younger than Non-triple negative tumors. For the targerted therapy against triple negative tumor, we need to study the specific marker of these.
Definitive (chemo)radiotherapy in patients with esophageal cancer: A population-based study in northeast Netherlands.
Authors: Justin Kendrick Smit, Christina T. Muijs, Paul R. Timmer, Gabriel Paardekooper, Karin Muller, Dankert Woutersen, Veronique E. Mul, Jannet Beukema, Geke A. Hospers, Johannes A. Langendijk, John Theodorus Plukker
Journal: Journal of Clinical Oncology (2012)

83 Background: Definitive (chemo)radiation as primary treatment modality is offered to esophageal cancer (EC) patients, as an alternative for patients considered medically unfit for surgery or having irresectable tumors. We evaluated the results in our cohort to improve selection of patients for intensified non-surgical strategies and to identify which clinical factors have a prognostic impact on the overall (OS) and disease free survival (DFS). Methods: EC patients treated with definitive radiotherapy (RT) or chemoradiotherapy (CRT) from 4 radiotherapy referral centers between 1996 and 2008 were used. Only patients with squamouscellcarcinoma (SCC) or adenocarcinoma (AC) were included in the analyses. Results: In total 278 patients were identified of whom 106 (38.1%) were treated with CRT (platinum based, median 50.4 (46.8 – 70)Gy) and 172 (61.9%) with RT alone (median 60 (40-70)Gy). T- stage was cT1=5.6%;cT2=15.3%;cT3=60.9% and cT4=18.2%. Nodal stage consisted of cN0=35%;cN1=65%, including cM1a=5.8%. The male/female ratio was 78.3% to 21.7%. AC occurred in 57.6% and 42.4% had a SCC. The median age was 69 years. Median OS time was 11 (1-166) months with an OS of 45%, 22% and 6% and a DFS of 32%, 18% and 6% at 1, 2 and 5 years, respectively. There was no significant difference between the CRT and RT group in OS (p=0.09) and DFS (p=0.17). The DFS after 2 and 5 year was 25% and 12% for SCC patients versus 11% and 0% for AC patients (p=0.007). The OS at 2 and 5 year was 28% and 11% for SCC versus 14% and 0% for AC patients (p=0.020). Initial recurrence was seen locoregionally in 66.7% and distant metastases occurred in 33.3%. Common sites for distant recurrence were the liver with 52.4%, 17.5% bones and 15.5% lungs. Patients with SCC had a better response to (chemo)radiotherapy considering the OS (p=0.02, HR=0.7) and DFS (p=0.01, HR=0.69) in a multivariate analysis. Conclusions: Patients with a SCC esophageal tumor have better long-term results then AC patients after definitive (chemo)radiation. In this patient group SCC seems to be a strong prognostic factor for both OS and DFS. Furthermore the difference between RT and CRT is still small.
MiRNAs modulate gastric cancer drug response by affecting hypoxia signaling
Authors: K. Danza, A. Mangia, G. Simone, L. Saragoni, O. Brunetti, L. Palermo, M. Signorile, M. Monti, S. De Summa, N. Silvestris, S. Tommasi
Journal: Annals of Oncology (2015)
Low Dose Antithymocyte Globulin (ATG) for Graft-Versus-Host Disease (GVHD) Prophylaxis
Authors: Anand Tandra, Leland Metheny, David Yao, Paolo F. Caimi, Lauren Brister, Brenda Cooper, Hillard M. Lazarus, Ben K. Tomlinson, Ehsan Malek, Fahrettin Covut, Raisa Pinto, Marcos deLima
Journal: Blood (2016)
Characterization of antigen-specific T-cell activation and cytokine expression induced by sipuleucel-T.
Authors: N. A. Sheikh, J. D. Wesley, E. Chadwick, N. Perdue, C. P. dela Rosa, M. W. Frohlich, F. P. Stewart, D. L. Urdal
Journal: Journal of Clinical Oncology (2011)

155 Background: Sipuleucel-T (Provenge) is an autologous cellular immunotherapy designed to stimulate an immune response in men diagnosed with asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer. This study examined the role of GM-CSF in T cell activation and cytokine production in sipuleucel-T from men enrolled in phase III clinical trials (D9902B – IMPACT and P07-2 - PROACT). Methods: Sipuleucel-T is manufactured from peripheral blood mononuclear cells (PBMCs) isolated every two weeks by leukapheresis. PBMCs are cultured with PA2024, a recombinant human antigen consisting of prostatic acid phosphatase (PAP) and granulocyte macrophage-colony stimulating factor (GM-CSF), for two days and cultured cells are then infused into patients. After each leukapheresis, a proportion of the PMBCs were cultured ex vivo for two days with GM-CSF (sargromostim). The GM-CSF cultures were compared to sipuleucel-T for their T cell activation profiles, cytokine production, and upregulation of CD54 and CD86 using flow cytometry and MesoScale Discovery technologies. Results: Sipuleucel-T had increased APC activation-associated cytokines (IL-1a, IL-10, IL-12p70, IFNg and TNFa) and T cell activation- associated cytokines (IL-2, IL-4, IL-5, IL-6, IL-10, IL-13, IFNg and TNFa) with each treatment. In contrast, GM-CSF-cultured cells had lower levels of these cytokines. Both PA2024- and GM-CSF-cultured cells had upregulated CD54 and CD86. T cell (CD4+ and CD8+) activation-markers were increased upon PA2024 restimulation, as measured by CD134 (OX40), CD137 (4-1BB), CD278 (ICOS), and CD279 (PD-1) expression. Cells from PA2024-cultures, but not GM-CSF-cultures, displayed a generalized pattern of enhanced expression of the T cell activation markers at the second infusion compared to the first and third. Conclusions: These data indicate that T cell activation and enhanced cytokine expression are a consequence of priming after the first infusion. These effects are not driven by GM-CSF, as T cell activation and enhanced cytokine production were only observed in PA2024 cultures. [Table: see text]
Use of a High Sensitive Nanofluidic Array for the Detection of Rare Copies of BCR-ABL1 Transcript In Patients with Philadelphia-Positive Acute Lymphoblastic Leukemia (ALL).
Authors: Ilaria Iacobucci, Annalisa Lonetti, Anna Ferrari, Cristina Papayannidis, Simona Soverini, Stefania Paolini, Mariachiara Abbenante, Viviana Guadagnuolo, Sarah Parisi, Leonardo Potenza, Mario Luppi, Federica Cattina, Domenico Russo, Fabrizio Pane, Michele Baccarani, Giovanni Martinelli
Journal: Blood (2010)