tbuckley/cabot-search huggingface dataset:
A multicenter phase II trial of the LH-RH analogue and an aromatase inhibitor combination in premenopausal patients with advanced or recurrent breast cancer refractory to an LH-RH analogue with tamoxifen: JMTO BC08-01.
Authors: Reiki Nishimura, Keisei Anan, Yutaka Yamamoto, Kenji Higaki, Maki Tanaka, Kenji Shibuta, Yasuaki Sagara, Shinji Ohno, Shigeru Tsuyuki, Takahiro Mase, Satoshi Teramukai
Journal: Journal of Clinical Oncology (2012)

588 Background: The aim was to provide an endocrine therapy option against advanced (ABC) or recurrent breast cancer (RBC) in premenopausal women. We conducted an exploratory phase II trial in combination with an LH-RH analogue (LH-RHa) and an aromatase inhibitor (AI) to assess the efficacy and tolerability after failure of standard LH-RHa plus tamoxifen (TAM). Methods: Premenopausal patients (pts) with ER+ and/or PgR+ ABC or RBC refractory to LH-RHa + TAM were treated with LH-RHa (goserelin: GOS) and AI (anastrozole: ANA). The primary endpoint was an objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), clinical benefit rate (CBR) based on RECIST, and safety assessed using CTCAE ver. 3.0. Pts with only bone legions were assessed using the criteria by Japanese Breast Cancer Society (14th Ed.). Local assessment (CR, PR or long SD of 24 weeks or longer) was confirmed independently by two radiologists. Results: Between September 2008 and November 2010, 37 pts were enrolled at 10 clinical institutions in Japan. Eleven had recurrence either during, or within one year after the end of adjuvant GOS + TAM (including GOS + TAM followed by only TAM). The disease progressed in 26 women during GOS + TAM. Mean age and BMI were 43.5 years and 22.2 kg/m2, respectively. Thirty-five pts (94.6%) were ER+, and 36 pts (97.3%) were HER2- (one with unknown HER2 status). Non-endocrine treatment included chemotherapy (20 pts; 54%) and radiation therapy (13 pts; 35%). The viscera, soft tissue, and bones were treated in 17, 15 and 14 pts, respectively. Pts with both measurable lesions and bone metastasis, measurable lesions only, and only bone metastasis were 21 (57%), 15 (41%) and 1 (2%), respectively. ORR was 18.9% (95%CI: 8.0-35.2%, 1 CR and 6 PR cases), CBR 62.2% (23 pts, 95%CI: 44.8-77.5%), and median PFS was 7.2 months. Eight pts (21.6%) had adverse events, but none resulted in treatment discontinuation. GOS + ANA was well tolerated. Conclusions: LH-RHa (GOS) + ANA can be a subsequent endocrine treatment for premenopausal pts with ABC or RBC after failure of GOS + TAM.
A Randomized Phase II Neoadjuvant Study of Cisplatin, Paclitaxel With or Without Everolimus in Patients with Stage II/III Triple-Negative Breast Cancer (TNBC): Responses and Long-term Outcome Correlated with Increased Frequency of DNA Damage Response Gene Mutations, TNBC Subtype, AR Status, and Ki67
Authors: Bojana Jovanović, Ingrid A. Mayer, Erica L. Mayer, Vandana G. Abramson, Aditya Bardia, Melinda E. Sanders, M. Gabriela Kuba, Monica V. Estrada, J. Scott Beeler, Timothy M. Shaver, Kimberly C. Johnson, Violeta Sanchez, Jennifer M. Rosenbluth, Patrick M. Dillon, Andres Forero-Torres, Jenny C. Chang, Ingrid M. Meszoely, Ana M. Grau, Brian D. Lehmann, Yu Shyr, Quanhu Sheng, Sheau-Chiann Chen, Carlos L. Arteaga, Jennifer A. Pietenpol
Journal: Clinical Cancer Research (2017)

Abstract Purpose: Because of inherent disease heterogeneity, targeted therapies have eluded triple-negative breast cancer (TNBC), and biomarkers predictive of treatment response have not yet been identified. This study was designed to determine whether the mTOR inhibitor everolimus with cisplatin and paclitaxel would provide synergistic antitumor effects in TNBC. Methods: Patients with stage II/III TNBC were enrolled in a randomized phase II trial of preoperative weekly cisplatin, paclitaxel and daily everolimus or placebo for 12 weeks, until definitive surgery. Tumor specimens were obtained at baseline, cycle 1, and surgery. Primary endpoint was pathologic complete response (pCR); secondary endpoints included clinical responses, breast conservation rate, safety, and discovery of molecular features associated with outcome. Results: Between 2009 and 2013, 145 patients were accrued; 36% of patients in the everolimus arm and 49% of patients in the placebo arm achieved pCR; in each arm, 50% of patients achieved complete responses by imaging. Higher rates of neutropenia, mucositis, and transaminase elevation were seen with everolimus. Clinical response to therapy and long-term outcome correlated with increased frequency of DNA damage response (DDR) gene mutations, Basal-like1 and Mesenchymal TNBC-subtypes, AR-negative status, and high Ki67, but not with tumor-infiltrating lymphocytes. Conclusions: The paclitaxel/cisplatin combination was well tolerated and active, but addition of everolimus was associated with more adverse events without improvement in pCR or clinical response. However, discoveries made from correlative studies could lead to predictive TNBC biomarkers that may impact clinical decision-making and provide new avenues for mechanistic exploration that could lead to clinical utility. Clin Cancer Res; 23(15); 4035–45. ©2017 AACR.
Post-Engraftment Infections in Adult Patients Transplanted with Single Cord Blood Units Supported by Co-Infusion of Mobilized Purified Hematopoietic Stem Cells from a Third Party Donor.
Authors: J. Rafael Cabrera, Isabel Krsnik, Rafael Fores, Elena Ruiz, Guiomar Bautista, Belen Navarro, Jorge Gayoso, Santiago Gil, Carmen Regidor, Isabel Sanjuan, Emilio Ojeda, Jose A. Garcia-Marco, Manuel N. Fernandez
Journal: Blood (2005)
Safety, activity, and pharmacokinetics of an oral anaplastic lymphoma kinase (ALK) inhibitor, ASP3026, observed in a “fast follower” phase 1 trial design.
Authors: Michael L. Maitland, Sai-Hong Ignatius Ou, Anthony W. Tolcher, Patricia LoRusso, Erkut Bahceci, Howard A Ball, Jung Wook Park, Geoff Yuen, Luana Pesco Koplowitz, Tianhong Li
Journal: Journal of Clinical Oncology (2014)

2624^ Background: The efficient early development of agents intended for selected patient populations is challenging. ASP3026 is a selective, ATP-competitive, kinase inhibitor with in vitro IC50for ALK of 3.5 nM. Methods: Advancedsolid tumor patients (pts) received oral ASP3026 under fasting conditions without interruption in 3+3 dose escalation cohorts from 25 to 800 mg once daily (QD). The primary endpoint was to identify the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of ASP3026. To identify rapidly evidence of therapeutic activity a previously cleared cohort could enroll up to an additional 3 pts with advanced ALKdriven solid malignancies(ALK+) . A planned phase Ib expansion cohort was opened at the R2PD. RECIST 1.1 was used to determine response. Results: The dose escalation phase enrolled 33 pts, including 3 ALK+ pts , and the expansion cohort enrolled another 13 ALK+ pts [total pts N = 46; 48% men; median (range) age = 61 (19-77) years]. Three dose-limiting toxicities (DLTs) were observed: grade 2 nausea and vomiting leading to dose reduction at 525 mg QD; grade 3 rash at 800 mg QD leading to dose reduction and grade 3 ALT/AST elevation leading to study withdrawal at 800 mg QD, making 525 mg daily the MTD and RP2D. The most common adverse events of the entire cohort were: fatigue (44%), vomiting (39%), nausea (37%), and constipation (24%). Of 15 pts with ALK+ non-small cell lung cancer (NSCLC) who progressed on prior crizotinib 7 (44%) had a partial response (PR) and 8 (50%) had stable disease as the best response. The median progression free survival in the ALK+ pts was 5.9 (95% CI: 3.8-9.4) months. Eight pts were still receiving treatment at data cut off. There was no correlation between response and plasma ASP3026 concentrations (AUC and Cmax) in the ALK+ pts. ASP3026 demonstrated dose-proportionality for AUC and Cmax with a terminal half-life compatible with QD dosing. Conclusions: The "fast follower" design enabled enrollment of ALK+ pts who had partial responses before the MTD of 525mg QD was determined. ASP3026 had clinical activity in ALK+ NSCLC pts who progressed on crizotinib. Clinical trial information: NCT01401504.
Final Results of the Chrysalis Trial: A First-in-Human Phase 1/2 Dose-Escalation, Dose-Expansion Study of Gilteritinib (ASP2215) in Patients with Relapsed/Refractory Acute Myeloid Leukemia (R/R AML)
Authors: Alexander E. Perl, Jessica K. Altman, Jorge E. Cortes, Catherine C. Smith, Mark Litzow, Maria R. Baer, David F. Claxton, Harry P. Erba, Stanley C. Gill, Stuart L. Goldberg, Joseph G. Jurcic, Richard A. Larson, Charles Liu, Ellen K. Ritchie, Gary J. Schiller, Alexander I. Spira, Stephen A. Strickland, Raoul Tibes, Celalettin Ustun, Eunice S. Wang, Robert K. Stuart, Christoph Röllig, Andreas Neubauer, Giovanni Martinelli, Erkut Bahceci, Mark J. Levis
Journal: Blood (2016)
Cobblestone Area-Forming Cell (CAFC) Content of Cord Blood Does Not Predict Engraftment in Double Cord Blood Transplantation.
Authors: Simon N. Robinson, Marcos de Lima, Hong Yang, William K. Decker, Dongxia Xing, David Steiner, Jingjing Ng, Michael W. Thomas, Richard E. Champlin, Chitra M. Hosing, Paul J. Simmons, Nathalie Brouard, Shannon Kidd, Laurence Cooper, Patrick A. Zweidler-McKay, Elizabeth J. Shpall
Journal: Blood (2007)
Abstract IA14: PDX models in head and neck cancers: Present status and future application for immune-oriented biology and therapy development
Authors: Antonio Jimeno
Journal: Clinical Cancer Research (2016)

Abstract Targeted therapy development in head and neck squamous cell carcinoma (HNSCC) is challenging given the rarity of activating mutations. Additionally, HNSCC incidence is dramatically increasing related to human papillomavirus (HPV). We sought to develop an in vivo model derived from patients reflecting the evolving HNSCC epidemiologic landscape, and use it to identify new therapies. Primary and relapsed tumors from over 100 HNSCC patients, both HPV+ and HPV-, have been implanted on mice, giving rise to over 50 strains. Resulting xenografts were characterized by detecting key mutations, measuring protein expression by IHC and gene expression/pathway analysis by mRNA-sequencing. The genetic makeup of these tumors was consistent with the frequencies of TP53, PI3KCA, NOTCH1, and NOTCH2 mutations found in landmark genomic characterization of large HNSCC patient cohorts. Tumors maintained their original morphology, genetic profiles, and drug susceptibilities through serial passaging. Cancer cells deceive the host to create an advantageous microenvironment and evade immune surveillance. A limitation to studying human cancer is the limited availability of in vivo models with appropriate human stroma and immunity. To address this unmet need, we generated an allogeneic humanized mouse (aHM) model where HNSCC were implanted on NOD/SCID/IL2rg-/- (NSG) mice reconstituted with human hematopoietic stem cells (HSCs) and other precursors from an unrelated donor. In aHM, bone marrow-derived human immune and mesenchymal cells homed into the growing tumor and interacted with human cancer cells as they would in a patient, partially reversing the gene expression drift that occurs after tumor passage on immune compromised mice. Further work is aimed at improving upon this platform. In summary, we have developed a HNSCC model covering its clinical spectrum whose major genetic alterations and susceptibility to anticancer agents represent contemporary HNSCC. Then, we have generated an aHM model to enable immune biology and therapy exploration in HNSCC. These models will enable prospectively testing therapeutic-oriented hypotheses leading to enhanced precision medicine, especially in the field of immune therapy. Citation Format: Antonio Jimeno. PDX models in head and neck cancers: Present status and future application for immune-oriented biology and therapy development. [abstract]. In: Proceedings of the AACR Special Conference: Patient-Derived Cancer Models: Present and Future Applications from Basic Science to the Clinic; Feb 11-14, 2016; New Orleans, LA. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(16_Suppl):Abstract nr IA14.
Phase II Study of Sphingosomal Vincristine in CHOP+/ − Rituximab for Patients with Aggressive Non-Hodgkin’s Lymphoma (NHL): Promising 3 Year Follow-Up Results in Elderly Patients.
Authors: Maria Alma Rodriguez, Nam H. Dang, Luis Fayad, Andre Goy, Fredrick Hagemeister, Peter McLaughlin, Barbara Pro, Jorge Romaguera, Anas Younes, Fernando Cabanillas
Journal: Blood (2005)
SiRNA Delivery with PEGylated Graphene Oxide Nanosheets for Combined Photothermal and Genetherapy for Pancreatic Cancer
Authors: Feng Yin, Kuan Hu, Yangzi Chen, Mengying Yu, Dongyuan Wang, Qianqian Wang, Ken-Tye Yong, Fei Lu, Yongye Liang, Zigang Li
Journal: Theranostics (2017)

Since the successful exfoliation of graphene from graphite in 2004, graphene and graphene oxide (GO) have been considered the most promising two-dimensional (2D) nanomaterials with distinguished physical and chemical characteristics and have attracted great attention in many different fields. Graphene oxide is well-known for its distinct physiochemical properties and shows only minimal cytotoxicity compared to carbon nanotubes. Until now, only limited efforts have been invested in utilizing GO for gene therapy in pancreatic cancer treatments. In this study, we utilized multi-functionalized monolayer GO as a gene delivery system to efficiently co-deliver HDAC1 and K-Ras siRNAs (small interfering RNAs targeting the HDAC1 gene and the G12C mutant K-Ras gene, respectively) to specifically target pancreatic cancer cells MIA PaCa-2. The systematic mechanistic elucidation of the dual gene silencing effects indicated the inactivation of both the HDAC1 and the K-Ras gene, thereby causing apoptosis, proliferation inhibition and cell cycle arrest in treated MIA PaCa-2 cells. The synergistic combination of gene silencing and NIR light thermotherapy showed significant anticancer efficacy, inhibiting in vivo tumor volume growth by >80%. Furthermore, GO can be metabolized in the mouse model within a reasonable period of time without obvious side effects. Based on preliminary in vivo application, this study for the first time indicates the promising potential of functionalized GO as a vehicle for gene therapy delivery with low toxicity for the treatment of pancreatic adenocarcinoma.
The utility of 18-F-fluorodeoxyglucose positron emission tomography in evaluation of bone marrow involvement by non-Hodgkin lymphoma (NHL)
Authors: A. Muslimani, H. Farag, S. Francis, T. P. Spiro, H. A. Daw, A. A. Chaudhry, V. C. Chan
Journal: Journal of Clinical Oncology (2007)

8077 Introduction: In NHL, the anatomic extent of the disease is an important factor influencing the overall survival. Clinically, NHLs are classified as indolent, aggressive, or highly aggressive. Bone marrow (BM) involvement is a sign of extensive disease, and iliac crest (IC) BM biopsy (BMB) is the established method for the detection of BM infiltration. However, IC BMB is associated with a high rate of false- negative result. We assess the ability of 18 F-FDG PET scan to ascertain the presence of BM involvement in NHL. Methods: We retrospectively reviewed charts from January 2002 through November 2006 of histologically proven NHLs. 87 patients (pts) were eligible for our study (38 males, 49 females; age range 42–81 years). All pts were examined by whole-body 18 F-FDG-PET scan for initial staging, and all had unilateral posterior IC BMB. BM involvement was established following the result of 1) unilateral posterior IC BMB, and 2) image-guided BMB following positive 18 F-FDG-PET scan in selected patients. Results: Among the PET+ / IC BMB- group, 3 pts had a positive CT-scan guided BMB at the site of involvement detected by the 18 F-FDG-PET scan (2 from the humerus,1 from the femur); the remaining 7 pts did not have a site-directed biopsy. Our data demonstrate an overall sensitivity of 0.76 for the PET scan detecting BM involvement in all pts and specificity of 0.88. We point out that the 0.88 specificity may be spuriously low, this is a result of the fact that of the 10 PET+ / IC BMB- pts 7 have not had directed biopsy to the site of involvement detected by the 18 F-FDG- PET-scan. Further analysis revealed no significant difference between the sensitivity (P = 0.21) and specificity (p = 0.99) between I- NHL and A/HA- NHL groups. Conclusion: 18 F-FDG-PET scan shows potential to detect BM involvement in NHL. In particular, image-guided repeat BMB may be considered in pts with negative initial IC BMB, whose 18 F-FDG-PET scan demonstrates BM involvement in a different site. No significant financial relationships to disclose. [Table: see text]
PP41. TARGETING GLIOMA MIGRATION WITH THE HISTONE DEACETYLASE INHIBITOR MI192
Authors: Ms Shaminder Kaur Bhandal, Mr Nicholas Radcliffe, Dr Filomena Esteves, Mrs Ruth Morton, Prof Ronald Grigg, Dr Marjorie Boissinot, Prof Susan Short, Dr Anke Bruning-Richardson
Journal: Neuro-Oncology (2017)

INTRODUCTION: High-grade gliomas feature prominently among the most devastating cancers due to their prevalence in the younger population, highly invasive nature and low 5-year survival. Despite a combined treatment regime of surgical resection, radiation therapy and chemotherapy most patients die within 1 year of initial diagnosis. Alternative, novel ways to treat these tumours are urgently required. Histone deacetylase (HDAC) are important regulators of chromatin remodelling and gene expression and have been shown to be involved in cancer. There is an increasing interest in the study and development of HDAC inhibitors towards clinical application. Moreover, they have been recently reported to inhibit cell migration due to their modulation of tubulin acetylation. Thus HDAC inhibitors represent attractive candidates for chemotherapeutics especially when considering the infiltrative nature of high-grade gliomas. Here, the specific HDAC2/3 inhibitor MI192 developed at Leeds University was investigated for its ability to inhibit 2D and 3D migration of two established adult glioma cell lines. METHODS: U87 and U251 cell lines were used for migration and cytoskeletal studies in 2D and 3D assays. The HDAC inhibitor MI192 was assessed for its ability to inhibit migration alongside LiCl and Bio-Indirubin, two anti-migratory drugs commonly used in glioma in vitro studies. RESULTS: In random migration (2D) the MI192 inhibitor adversely affected the migratory ability of U87 and U251 as evidenced by reduced cell velocity and also cell displacement. This effect was more pronounced in U251 than U87. Immunofluorescence studies of the MI192-treated cells revealed an increase in the acetylation of tubulin in U87, whilst proliferation and apoptosis status remained unchanged. U251 did not appear to show increased levels of tubulin acetylation. In a 3D spheroid invasion assay U87 migration was inhibited by MI192 at 1 uM concentration, but not at 0.1 or 0.01 uM, whereas we did not see a significant change in U251. Immunohistochemistry of the treated spheroids revealed that proliferation was adversely affected in both the core and migratory cells in U87 spheroids with MI192 at a concentration of 1 uM but not in U251 spheroids. Tubulin acetylation appeared more pronounced in U251 after MI192 treatment. In addition, SOX-2 (as a marker of stemness) was reduced in both U251 cores and migratory cells with MI192. CONCLUSION: In addition to its activity as a chromatin remodelling inhibitor, MI192 appears to inhibit glioma cell migration via hyperacetylation of tubulin and possibly microtubule stabilisation in a cell line and topography dependent manner. Thus, the HDAC2/3 inhibitor MI192 may prove useful in targeting migration in certain subtypes of glioma cell.
Moderate Reduction in LVEF Is Associated with an Increased Risk of Post-HSCT Symptomatic Cardiomyopathy
Authors: Kinjal Parikh, Lekha Mikkilineni, Fern Martin, Dolores Grosso, Benjamin Leiby, Onder Alpdogan, Matthew Carabasi, Margaret Kasner, Thomas R. Klumpp, Ubaldo Martinez Outschoorn, Manish Sharma, Mark Weiss, John L. Wagner, Neal Flomenberg, Joanne Filicko-O'Hara
Journal: Blood (2015)
An Analysis of Angiotensin Converting Enzyme Gene Polymorphisms and Non-Infectious Pulmonary Dysfunction after Hematopoietic Stem Cell Transplantation.
Authors: Makoto Onizuka, Kiyoshi Ando, Kengi Kishi, Hiroshi Kawada, Yasuo Morishima, Tomomitsu Hotta, Hidetoshi Inoko
Journal: Blood (2005)
Conversion-to-open in laparoscopic appendectomy: A cohort analysis of risk factors and outcomes
Authors: Brendan M. Finnerty, Xian Wu, Gregory P. Giambrone, Licia K. Gaber-Baylis, Ramin Zabih, Akshay Bhat, Rasa Zarnegar, Alfons Pomp, Peter Fleischut, Cheguevara Afaneh
Journal: International Journal of Surgery (2017)
Abstract PR01: Ductal pancreatic cancer modeling and drug screening using human pluripotent stem cell and patient-derived tumor organoids
Authors: Senthil K. Muthuswamy
Journal: Clinical Cancer Research (2016)

Abstract There are few in vitro models of exocrine pancreas development and primary human pancreatic adenocarcinoma (PDAC). We establish three-dimensional culture conditions to induce the differentiation of human pluripotent stem cells (PSCs) into exocrine progenitor organoids that form ductal and acinar structures in culture and in vivo. Expression of mutant KRAS or TP53 in progenitor organoids induces mutation-specific phenotypes in culture and in vivo. Expression of TP53R175H induced cytosolic SOX9 localization. In patient tumors bearing TP53 mutations, SOX9 was cytoplasmic and associated with mortality. Culture conditions are also defined for clonal generation of tumor organoids from freshly resected PDAC. Tumor organoids maintain the differentiation status, histoarchitecture, phenotypic heterogeneity of the primary tumor, and retain patient-specific physiologic changes including hypoxia, oxygen consumption, epigenetic marks, and differential sensitivity to EZH2 inhibition. Thus, pancreatic progenitor organoids and tumor organoids can be used to model PDAC and for drug screening to identify precision therapy strategies. This abstract is also being presented as Poster B10. Citation Format: Senthil K. Muthuswamy. Ductal pancreatic cancer modeling and drug screening using human pluripotent stem cell and patient-derived tumor organoids. [abstract]. In: Proceedings of the AACR Special Conference: Patient-Derived Cancer Models: Present and Future Applications from Basic Science to the Clinic; Feb 11-14, 2016; New Orleans, LA. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(16_Suppl):Abstract nr PR01.
Role of Hypoxia in the Progression and Dissemination of Multiple Myeloma.
Authors: Abdel Kareem Azab, Phong Quang, Feda Azab, Aldo M. Roccaro, Antonio Sacco, Judith M. Runnels, Hai T. Ngo, Molly R Melhem, Patricia Maiso, Kenneth C. Anderson, Charles P. Lin, Irene M. Ghobrial
Journal: Blood (2009)
Unexpectedly High Incidence of Interstitial Pneumonia in Newly Diagnosed Diffuse Large B-Cell Lymphoma Treated with Rituximab-CHOP-14 Supported with Pegfilgrastim.
Authors: Ercole Brusamolino, Chiara Rusconi, Luigi Montalbetti, Livio Gargantini, Graziella Pinotti, Lilj Uziel, Sergio Fava, Luigi Rigacci, Guido Pagnucco, Guido Frigerio, Mario Fiumano, Luciano Banfi, Francesco Rodeghiero, Giovanni Ucci, Alberto De Paoli, Giuseppe Attardo Parrinello, Enrica Morra, Mario Lazzarino
Journal: Blood (2005)