tbuckley/cabot-search huggingface dataset:
The novel cytotoxicity of neutrophils in the peripheral blood of patients with breast cancer versus healthy women.
Authors: Z. Granot, E. A. Comen, L. Norton, R. Benezra
Journal: Journal of Clinical Oncology (2011)

e21055 Background: Using murine mammary tumor models, recent research conducted by our laboratory at the Sloan-Kettering Institute indicates that select neutrophils are mobilized and entrained by a primary breast tumor and uniquely have the capacity to inhibit metastatic seeding in the lung (Granot Z et al. unpublished). We sought to determine whether entrainment of cytotoxic neutrophils also occurs in blood samples from women with newly diagnosed breast cancer as contrasted to those garnered from healthy women. Methods: Subjects were 14 newly diagnosed pre-operative breast cancer patients without evidence of metastatic disease, 9 healthy female volunteers with no history of any cancer and 2 patients with newly diagnosed DCIS. Neutrophils were purified from the blood samples. Cytotoxicity was evaluated by incubating isolated neutrophils with luciferase labeled MDA-MB-231 cells. Luciferase activity, as a reflection of % cell kill, was measured using a Bio-Tek microplate luminescence reader. Results: Significant cytotoxicity was notably observed when MDA-MB-231 cells were co-cultured with neutrophils purified from patients with invasive tumors. Pre-operative breast cancer patients (n=14) had a cell kill range of 0-30% (mean = 13.9%), whereas healthy subjects (n=9) had a cell kill range of 0.2-8% (mean = 2.6%), p<0.001. DCIS patients (N=2) had a cell kill range of 3-4% (mean = 3.65). Conclusions: To date, this preliminary work is the first to demonstrate the cytotoxic role of select neutrophils in the peripheral blood of breast cancer patients as contrasted with those from women without breast cancer. Further studies are needed to evaluate the prognostic and therapeutic role of cytotoxic neutrophils.
Women’s Mental Health and Well-being 5 Years After Receiving or Being Denied an Abortion
Authors: M. Antonia Biggs, Ushma D. Upadhyay, Charles E. McCulloch, Diana G. Foster
Journal: JAMA Psychiatry (2016)

The idea that abortion leads to adverse psychological outcomes has been the basis for legislation mandating counseling before obtaining an abortion and other policies to restrict access to abortion.To assess women's psychological well-being 5 years after receiving or being denied an abortion.This study presents data from the Turnaway Study, a prospective longitudinal study with a quasi-experimental design. Women were recruited from January 1, 2008, to December 31, 2010, from 30 abortion facilities in 21 states throughout the United States, interviewed via telephone 1 week after seeking an abortion, and then interviewed semiannually for 5 years, totaling 11 interview waves. Interviews were completed January 31, 2016. We examined the psychological trajectories of women who received abortions just under the facility's gestational limit (near-limit group) and compared them with women who sought but were denied an abortion because they were just beyond the facility gestational limit (turnaway group, which includes the turnaway-birth and turnaway-no-birth groups). We used mixed effects linear and logistic regression analyses to assess whether psychological trajectories differed by study group.We included 6 measures of mental health and well-being: 2 measures of depression and 2 measures of anxiety assessed using the Brief Symptom Inventory, as well as self-esteem, and life satisfaction.Of the 956 women (mean [SD] age, 24.9 [5.8] years) in the study, at 1 week after seeking an abortion, compared with the near-limit group, women denied an abortion reported more anxiety symptoms (turnaway-births, 0.57; 95% CI, 0.01 to 1.13; turnaway-no-births, 2.29; 95% CI, 1.39 to 3.18), lower self-esteem (turnaway-births, -0.33; 95% CI, -0.56 to -0.09; turnaway-no-births, -0.40; 95% CI, -0.78 to -0.02), lower life satisfaction (turnaway-births, -0.16; 95% CI, -0.38 to 0.06; turnaway-no-births, -0.41; 95% CI, -0.77 to -0.06), and similar levels of depression (turnaway-births, 0.13; 95% CI, -0.46 to 0.72; turnaway-no-births, 0.44; 95% CI, -0.50 to 1.39).In this study, compared with having an abortion, being denied an abortion may be associated with greater risk of initially experiencing adverse psychological outcomes. Psychological well-being improved over time so that both groups of women eventually converged. These findings do not support policies that restrict women's access to abortion on the basis that abortion harms women's mental health.
SL-801, a Novel, Reversible Inhibitor of Exportin-1 (XPO1) / Chromosome Region Maintenance-1 (CRM1) with Broad and Potent Anti-Cancer Activity
Authors: Janice Chen, Christopher L. Brooks, Peter McDonald, Jonathan D. Schwartz, Rebecca S. Schneider, Keiichi Sakakibara, Naoya Saito, Takuji Sato, Takumi Kawabe, Eric K. Rowinsky
Journal: Blood (2015)
Abstract 5484: FGFR2 amplification is predictive of sensitivity to regorafenib in gastric and colorectal cancers
Authors: Yongjun Cha, Hwang-Phill Kim, Sae-won Han, Jiyeon Yun, Sang-Hyun Song, Tae-You Kim
Journal: Cancer Research (2015)

Abstract Purpose Regorafenib is an orally bioavailable, small molecular multikinase inhibitor of VEGFR, PDGFR, FGFR, KIT, RET, BRAF, BRAFV600E, CRAF, and TIE2. Although regorafenib has demonstrated survival benefits in patients with metastatic colorectal and gastrointestinal stromal tumors, there is no proven biomarker predicting sensitivity to regorafenib. We investigated preclinical activity of regorafenib in gastric and colorectal cancer cell-lines to identify genetic alterations associated with sensitivity to regorafenib. Methods Fourteen gastric cancer cell lines and 18 colorectal cancer cell lines were screened for regorafenib sensitivity with cell proliferation assays. We performed targeted exome and transcriptome sequencing of the cell lines to identify genetic alterations associated with sensitivity to regorafenib. Mechanisms of regorafenib sensitivity were investigated in regorafenib sensitive cell lines with immunoblotting and flow cytometry. Results Two gastric (SNU-16, KATO-III) and 1 colorectal (NCI-H716) cancer cells were sensitive to regorafenib with GI50 values of less than 1 μM. Mutation profiles and mRNA expression levels of regorafenib target molecules in regorafenib sensitive and insensitive cell lines demonstrated that amplification of FGFR2 was the only genetic alteration associated with in vitro sensitivity to regorafenib. FGFR2 amplified gastric (SNU-16, KATO-III) and colorectal (NCI-H716) cancer cell lines revealed activated signaling through FGFR2 pathway, and knock-down of FGFR2 with siRNA significantly repressed cellular growth rate and decreased sensitivity to regorafenib. Regorafenib effectively inhibited phosphorylation of FGFR2 and its downstream signaling molecules in dose-dependent manner selectively in FGFR2 amplified cells. In cell cycle analysis, regorafenib induced G1/S arrest (SNU-16, KATO-III) and apoptosis (NCI-H716), however no significant changes were seen in cell lines without FGFR2 amplification. Conclusions Signaling through FGFR2 pathway plays a key role in cellular growth and survival in FGFR2 amplified cancers. Regorafenib effectively abrogates activated FGFR2 signaling in FGFR2 amplified gastric and colorectal cancer cells, and therefore should be considered for integration into treatment in patients with FGFR2 amplified gastric and colorectal cancers. Citation Format: Yongjun Cha, Hwang-Phill Kim, Sae-won Han, Jiyeon Yun, Sang-Hyun Song, Tae-You Kim. FGFR2 amplification is predictive of sensitivity to regorafenib in gastric and colorectal cancers. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5484. doi:10.1158/1538-7445.AM2015-5484
Outcome of Children with T-Cell Acute Lymphoblastic Leukemia (T-ALL) and Standard Risk (SR) Features: Results of CCG-1952, CCG-1991 and POG 9404.
Authors: Yousif Matloub, B.L. Asselin, Linda C. Stork, Meenakshi Devidas, Harland Sather, James Nachman, Bruce Camitta, Paul S. Gaynon
Journal: Blood (2004)
Types and Sub Types of Von Willebrand Disease Classified on the Basis of Multimer Analysis
Authors: Arshi Naz, Hamideh Yadegari, Julia Driesen, Johannes Oldenburg, Shariq Ahmed, Shahla Tariq, Samina Tufail Amanat, fazal-E- Razik, Nisar Ahmed, Mohammad Nadeem, Tahir Shamsi
Journal: Blood (2015)
GSK1120212, a MEK1/MEK2 Inhibitor, Demonstrates Acceptable Tolerability and Preliminary Activity In a Dose Rising Trial In Subjects with AML and Other Hematologic Malignancies
Authors: Gautam Borthakur, James M. Foran, Tapan Kadia, Elias Jabbour, Paul Wissel, Donna Cox, Yanmei Xu, John Bauman, Melanie Baccus, Jeanne Connor, Jorge E. Cortes, Hagop Kantarjian
Journal: Blood (2010)
Vascular Endothelial Cells Promote the Viability of CLL Cells Via the up-Regulation of Bcl-2 and Bcl-XL
Authors: Andrea G S. Buggins, Piers EM Patten, Satyen H Gohil, Ghulam J Mufti, Nicholas Shaun B. Thomas, Stephen Devereux
Journal: Blood (2008)
Abstract 2546: HDAC and Hsp90 inhibition as therapeutic strategy for translocation renal cell carcinoma
Authors: Sheng-Yu Ku, Swathi Ramakrishnan, Eric Ciamporcero, Bo Xu, Gissou Azabdaftari, Richard Cheney, Roberto Pili
Journal: Cancer Research (2015)

Abstract Background: Xp11.2 translocation renal cell carcinoma (tRCC) is an aggressive subtype of kidney cancer, which mainly occurs in young patients. The prevalence of this disease is about 30% in pediatric RCC, but ∼1% in adult RCC cases. Patients with tRCC are refractory to standard therapies for clear cell RCC. Therefore, there is no efficient treatment for this type of kidney cancer. The tRCC harbors gene fusions involving the TFE3 transcription factor on chromosome X with several partner genes, leading to TFE3 elevation in the cell nucleus, but its function remains unclear. We have successfully established a cell line and patient-derived xenograft from a tRCC patient to develop rational therapeutic strategies and understand the tumor biology. Methods: We have utilized a feeder layer containing a ROCK inhibitor to favorably generate a cell line, 277T, from a young tRCC patient. Also, we have implanted tumor samples from the patient subcutaneously into SCID mice to establish a patient-derived xenograft model, RP-R-07, and continuously maintain tumor growth in vivo. Cells were treated with different drugs, and then assessed by MTT assay and trypan blue staining for growth inhibition and cell death investigations. TFE3 expression in cells and tumors were detected by immunofluorescence and immunohistochemistry. The combined drug effects were determined by CalcuSyn analysis. Results: Our preliminary results demonstrated that TFE3 is predominately expressing in the nucleus of 277T cells and RP-R-07 tumor model compared to other subtypes of RCC by immunofluorescence and immunohistochemistry, respectively. Further, we treated 277T cells with several cytotoxic drugs showing that the cells didn't respond to docetaxel, doxorubicin, rapamycin, or a PI3K-mTOR inhibitor, but were sensitive to the Hsp90 inhibitor AUY922, and the HDAC inhibitor LBH589. Moreover, combining both AUY922 and LBH589 induced greater cell death compared to each single treatment (73% vs 41% for LBH589; 73% vs 19% for AUY922). In addition, an in vivo experiment indicated that LBH589 did inhibit tumor growth. Conclusions: Overall our results indicate that tRCC is sensitive to HSP90 and HDAC inhibitors both in vitro and in vivo. The combination of LBH589 and AUY922 represents a promising strategy for treating tRCC Citation Format: Sheng-Yu Ku, Swathi Ramakrishnan, Eric Ciamporcero, Bo Xu, Gissou Azabdaftari, Richard Cheney, Roberto Pili. HDAC and Hsp90 inhibition as therapeutic strategy for translocation renal cell carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2546. doi:10.1158/1538-7445.AM2015-2546
TET 2 Alterations in Myeloid Malignancies, Impact on Clinical Characteristics, Outcome, and Disease Predisposition
Authors: Aziz Nazha, Manja Meggendorfer, Niroshan Nadarajah, Kassy E Kneen, Tomas Radivoyevitch, Bartlomiej Przychodzen, Hideki Makishima, Bhumika J. Patel, Srinivasa R. Sanikommu, Sean Hobson, Mridul Mukherji, Mikkael A. Sekeres, Torsten Haferlach, Jaroslaw P. Maciejewski
Journal: Blood (2015)
Non-Myeloablative T-Cell Depleted (TCD) Haploidentical Hematopoietic Cell Transplantation (HCT) Followed by Donor Leukocyte Infusion(s) for Hematologic Malignancies: The MGH Experience.
Authors: Bimalangshu R. Dey, Andrew J. Yee, Steven McAfee, Christine Dube, Karen Ballen, Eyal Attar, Christine Colby, Susan Saidman, Karen Malikowski, Frederic Preffer, Megan Sykes, Thomas R. Spitzer
Journal: Blood (2007)
Abstract 1513: ALDH1 and podoplanin expression in oral leukoplakia: Correlate with malignant transformaion risk
Authors: Umma Habiba, Masanobu Shindoh
Journal: Cancer Research (2015)

Abstract Oral leukoplakia (OL) is the clinically diagnosed preneoplastic lesion in the oral cavity with an increased oral cancer risk. However, the risk of malignant transformation of OL is still difficult to assess. The objective of this study was to examine the expression patterns of ALDH1 and Podoplanin (PD) and determine their role in predicting oral cancer development in patients with OL. In a retrospective follow-up study, the expression patterns of ALDH1 and PD were determined using immunohistochemistry in samples from 79 patients with OL, including patients with untransformed lesions (n = 42) and patients with malignant transformed lesions (n = 37). The association between protein expression patterns and clinicopathologic parameters including oral cancer free survival (OCFS) was analyzed during a mean follow up period of 3.5 years. ALDH1 and PD expression was observed in 48 (61%) and 53 (67%) patients respectively. Kaplan-Meier analysis showed that the expression of ALDH1 and PD was correlated with the risk of progression to oral cancer (P = &amp;lt; 0.05). Multivariate analysis revealed that ALDH1 and PD expression was associated with 3.02 folds and 2.62 folds of increase risk of malignant transformation, respectively. Meanwhile, the malignant transformation risk of OL was considerably higher in cases with both ALDH1 and PD expression (P = 0.000). Taken together, our data indicated that ALDH1 and PD expression patterns in OL were associated with oral cancer development, suggesting that ALDH1 and PD could be useful biomarkers to identify OL patient with substantially high oral cancer risk. Citation Format: Umma Habiba, Masanobu Shindoh. ALDH1 and podoplanin expression in oral leukoplakia: Correlate with malignant transformaion risk. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1513. doi:10.1158/1538-7445.AM2015-1513
Comparative Efficacy of Tandem Autologous Versus Autologous Followed by Allogeneic Hematopoietic Cell Transplantation in Patients with Multiple Myeloma: A Systematic Review and Meta-Analysis
Authors: Mohamed A. Kharfan-Dabaja, Mehdi Hamadani, Tea Reljic, William I. Bensinger, Benjamin Djulbegovic, Ambuj Kumar
Journal: Blood (2012)
Chromosome 7 Abnormalities in Allogeneic Transplantation for AML and MDS
Authors: Vamsi Kota, Rima M. Saliba, Ulas D. Bayraktar, Amer Beitinjaneh, Julianne J Chen, Simrit Parmar, Sergio A Giralt, Gabriela Rondon, Stefan O Ciurea, Partow Kebriaei, Muzaffar H Qazilbash, Borje S Andersson, Richard Champlin, Marcos De Lima
Journal: Blood (2011)
Abstract 2444: Directed evolution strategy for generating of novel zinc finger peptides with affinity for gapped DNA
Authors: Dylan Plaskon, Rachel M. Guerra, Connor P. McGuckin, Vania Lopez Ruiz, Colin T. Sheehan, Ryan A. Weeks, Dylan Cincotta, Kevin P. Rice
Journal: Cancer Research (2015)

Abstract A significant fraction of oncologists’ chemotherapeutic arsenal consists of agents that cause DNA damage. Repair proteins that recognize aberrant DNA structural features mitigate this damage and thus the efficacy of such anticancer drugs. DNA damage recognition is also crucial for genomic stability, and thus avoidance of carcinogenesis, in healthy cells. The DNA repair enzymes poly(ADP-ribose) polymerase (PARP) and DNA ligase III use similar zinc finger motifs to facilitate this sequence-independent DNA recognition. Reported here is a strategy to model these protein-DNA interactions using small proteins. Proteins with high affinity for gapped DNA are selected from highly diverse libraries of proteins, based on PARP-like zinc finger domains, using phage display. These populations were engineered at the DNA level, using two parallel approaches, with built-in randomization then cloned into viral chromosomes. The de novo approach involved synthetic oligonucleotides with specific random codons. In addition, the gene encoding the second PARP zinc finger was cloned from human cells and subjected to 30 cycles of error-prone PCR with a mutation rate of 0.02 per nucleotide. From each approach, a library of approximately 10 billion distinct phage-displayed variants is exposed to immobilized DNA molecules featuring a gapped DNA construct. Selected molecules are either identified by DNA sequencing or subjected to further selection after amplification in bacterial culture. A preliminary selection against nicked DNA yielded a single, truncated peptide after four rounds of selection. In subsequent experiments, Illumina sequencing will identify consensus sequences that will be cloned into plasmids appropriate for expression in bacteria. Molecules discovered by this strategy will help illuminate the structure-function relationships of proteins that recognize distinct DNA structures and may lead to new anticancer approaches. Citation Format: Dylan Plaskon, Rachel M. Guerra, Connor P. McGuckin, Vania Lopez Ruiz, Colin T. Sheehan, Ryan A. Weeks, Dylan Cincotta, Kevin P. Rice. Directed evolution strategy for generating of novel zinc finger peptides with affinity for gapped DNA. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2444. doi:10.1158/1538-7445.AM2015-2444
Von Willebrand Factor Propeptide: Response to 1-Deamino-8-D-Arginine Vasopressin and Investigation of Relationship with Plasma Clearance of Von Willebrand Factor Antigen in Type 1 Von Willebrand Disease.
Authors: Carolyn M. Millar, Anne F. Riddell, Anja Griffeon, Simon A. Brown, Herm-Jan Brinkman, Jan A. van Mourik
Journal: Blood (2005)
Abstract LB-244: Amino acid deprivation selectively targets multidrug-resistant breast cancer cells
Authors: Catherine A. Del Vecchio, Yuxiong Feng, Ethan S. Sokol, Erik J. Tillman, Sandhya Sanduja, Ferenc Reinhardt, Piyush B. Gupta
Journal: Cancer Research (2015)

Abstract Tumor recurrence and metastasis underlie the majority of cancer-related deaths. Cancer cells that recur or metastasize are often both de-differentiated and multidrug resistant, but the mechanistic basis for this has been poorly understood. We have recently shown that de-differentiation promotes multidrug resistance by activating Nrf2, which stimulates transcription of drug efflux pumps and enzymes that scavenge reactive oxygen species (ROS). De-differentiation activates Nrf2 by a non-canonical mechanism involving its phosphorylation by the ER membrane kinase PERK. PERK-Nrf2 signaling protects de-differentiated cells from chemotherapy, and inhibiting this signaling axis re-sensitizes de-differentiated cancer cells to treatment. To further explore this pathway we profiled the effects of PERK inhibition on global gene expression in both differentiated and de-differentiated cells upon treatment with chemotherapy. This analysis showed that PERK inhibition results in an amino acid deprivation phenotype, and suggested that de-differentiated cells may be sensitive to perturbations in amino acid availability. Consistent with this, we found that the aminopeptidase inhibitor Tosedostat was selectively toxic to de-differentiated breast cancer cells when given in combination with chemotherapy. Our findings identify a novel vulnerability of therapy-resistant breast cancer cells, and suggest that targeting amino acid availability in combination with chemotherapy could be an effective treatment for aggressive breast cancers that are multidrug resistant. Citation Format: Catherine A. Del Vecchio, Yuxiong Feng, Ethan S. Sokol, Erik J. Tillman, Sandhya Sanduja, Ferenc Reinhardt, Piyush B. Gupta. Amino acid deprivation selectively targets multidrug-resistant breast cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-244. doi:10.1158/1538-7445.AM2015-LB-244
Bortezomib with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in patients with newly diagnosed myeloma without intent for immediate autologous stem-cell transplant (SWOG S0777): a randomised, open-label, phase 3 trial
Authors: Brian G M Durie, Antje Hoering, Muneer H Abidi, S Vincent Rajkumar, Joshua Epstein, Stephen P Kahanic, Mohan Thakuri, Frederic Reu, Christopher M Reynolds, Rachael Sexton, Robert Z Orlowski, Bart Barlogie, Angela Dispenzieri
Journal: The Lancet (2016)
The Outcome of Hematopoietic Cell Transplantation (HCT) for Myelodysplastic Syndrome (MDS) in Adults ≥65 Years of Age: First Report of the Coverage with Evidence Development (CED) in Medicare Beneficiaries
Authors: Ehab Atallah, Tanya L. Pedersen, Erica D. Warlick, Anne Dircks, Daniel Weisdorf, Mary M. Horowitz, J. Douglas Rizzo
Journal: Blood (2012)