tbuckley/cabot-search huggingface dataset:
Efficacy and toxicity of ICE (ifosphamide, carboplatin, and etoposide) and IIVP (ifosphamide, idarubicin, and etoposide) salvage chemotherapy regimens in relapse/refractory Hodgkin lymphoma patients.
Authors: C. Arslan, E. Ozdemir, I. Barista, A. Turker, A. Kars, Y. Y. Ozisik, E. Kansu
Journal: Journal of Clinical Oncology (2011)

e18563 Background: We aimed to study the efficacy and toxicity of salvage chemotherapy (SC) regimens ICE (ifosphamide, carboplatin and etoposide) and IIVP (ifosphamide, idarubicin, etoposide) in relapse/refractory Hodgkin lymphoma (HL) patients. Methods: Data of relapse/refractory HL patients followed at our institute between years 2002 and 2010 were analyzed rectrospectively. ICE protocol was adminestered as; ifosphamide (5 g/m2; d2), mesna (3 g/m2; d 2), carboplatin (AUC:5; d3), etoposide (100 mg/m2; d1-3). IIVP protocol was adminestered as ifosphamide (1 g/m2; d1-5), mesna (600 mg/m2; d1-5), etoposide (150 mg/m2; d1-3), idarubicin (10 mg/m2; d1,2). Results: There were 35 and 45 patients in ICE and IIVP groups, respectively. Nineteen (53%) in ICE and 31 (68.9%) in IIVP group were male patients. Median age was 27 (min-max:18-69) and 33 (min-max:17-66) in ICE and IIVP groups, respectively. Most frequent histologic subtypes were nodular sclerosing and mixed cellular in both groups. Fourteen (41.1%) patients in ICE and 29 (64.4%) in IIVP group were stage≤2. Most frequent first line treatment was ABVD in both group. Sixteen patients in ICE (45.7%) and 24 (53.3%) in IIVP group received radiotherapy prior to SC. All patients in IIVP and 30 (85.7%) in ICE groups received ≤3 cycles of SC. All patients were given primary GCSF prophylaxis.There were 22 (62.9%) responses in ICE and 31 (68.9%) in IIVP groups (p=.330). Responses in ICE and IIVP groups were as; CR: 6/13 (17.1/28.9%), PR: 16/18 (45.7/40%), SD:1/3 (2.9/6.7%) and refractory disease: 11/7 (31.4/15.6%), respectively (p=0.302). Grade 3-4 toxicities were seen in 20 (57.1%) patients in ICE and 33 (73.3%) in IIVP group (p=0.158). There were no difference between grade 3-4 hematological toxicities. But grade 3-4 thrombocytopenia was seen more frequent in IIVP (17;47%) than ICE (7;24%) group (p=0.055). There were 3 (8.6%) neutropenic fever in ICE and 12 (26.7%) in IIVP groups (p=0.062). There were no treatment related death. Conclusions: Efficacy and toxicity of ICE and IIVP regimens were similar. However CR and grade 3-4 thrombocytopenia rates were higher in IIVP group.
Active surveillance in asymptomatic or minimally symptomatic renal cell carcinoma: Retrospective analyses of a cohort of three oncological centers from Spain.
Authors: Maria Jove, Olatz Etxaniz, Nuria Sala, Albert Font, Laura Jimenez Colomo, Maria Saigi, Sabela Recalde, Valentín Navarro-Perez, Maria Pilar Barretina Ginesta, Maria Ochoa de Olza, Nuria Mulet, Xavier Garcia del Muro
Journal: Journal of Clinical Oncology (2015)

441 Background: Some patients (pt) with metastatic renal cell carcinoma (mRCC) have an indolent course. Treatment toxicities can worsen quality of life. Active surveillance (AS) in paucisymptomatic pts is an option often used but few data is available. Our aim is to analyze the impact of initial AS in a sequential therapy strategy in terms of overall survival (OS). Methods: Data frompt diagnosed with mRCC from January 2005 to December 2013 in 3 centres of Spain were retrospectively analyzed. AS subgroup was defined as pt with ≥6 months (m) between diagnosis and first-line (L) treatment (tto) start. A descriptive analysis and median OS (mOS) were performed comparing pt with or without AS (AS vs. tto &lt;6m). OS curve and medians were estimated using Kaplan Meier Method. A multivariate cox regression analyses with different prognostic factors was also realized. Results: From a cohort of 277 pt with mRCC, 69 pt (25%) were on initial AS and 208 pts on tto &lt;6m (75%). Median time on observation until systemic tto was started on pt on AS was 14 m 95%CI (17.6-26.02). Pt characteristics of AS vs tto &lt;6 m were: median age 63/60; males 70/72%; histology: 94/76% clear cell, 3/12% papillar, 0/4% chromophob; M1 at diagnosis: 22/48%; prognosis (Heng risk criteria): 0/17.% poor, 38.5/57% intermediate, 61.5/25% good; prior nephrectomy: 93/73%; number of metastatic locations (loc): 87/68% ≤2 loc, 12.5/32.5% ≥3 loc; lines of treatment: first L 46/53%, second L 38/23%, and third L 16/24%. When comparing exposure in months to each tto L, pt on AS had longer period of tto in second L (10.06/4.14 m, p=0.014). mOS were: 62 m 95%CI (52.97-71.03) vs. 22 m 95% CI (19.87-24.12) for AS/tto &lt;6 m respectively (p&lt;0.001) with statistical significance after multivariate analysis (Cox regression, HR=0.39; 95% CI, 0.25-0.63). Factors that independently influence on OS were: ≥2 M1 sites and papillar histology, negatively, and prior nephrectomy and &gt;1 year from diagnosis to M1, positively. Conclusions: Our results suggest that AS before starting first L of tto is not a detrimental action in a selected population of mRCC pt with good risk characteristics allowing them to remain free of therapy’s toxicity during a long time period.
Circulating Plasma Levels of Bone Morphogenic Protein Antagonist Gremlin-1 Are Increased in Patients with Pulmonary Arterial Hypertension
Authors: Jasmin Wellbrock, Jan K. Hennigs, Björn Schulz, Gabi Vohwinkel, Hans Jörg Baumann, Carsten Bokemeyer, Hans Klose, Walter Fiedler, Nicole Lüneburg
Journal: Blood (2012)
Tumor Deposits in Colorectal Cancer: Improving the Value of Modern Staging—A Systematic Review and Meta-Analysis
Authors: Iris D. Nagtegaal, Nikki Knijn, Niek Hugen, Helen C. Marshall, Kenichi Sugihara, Tibor Tot, Hideki Ueno, Philip Quirke
Journal: Journal of Clinical Oncology (2017)

Purpose Colorectal cancer (CRC) treatment is largely determined by tumor stage. Despite improvements made in the treatment of various types of metastatic disease, staging has not been refined. The role of tumor deposits (TDs) in staging remains debated. We have assessed the relation of TDs with metastatic pattern to evaluate whether TDs might add significant new information to staging. Methods We performed a systematic literature search that was focused on the role of TDs in CRC. Studies with neoadjuvant-treated patients were excluded. Data on stage, histologic factors, and outcome were extracted. Data from four large cohorts were analyzed for the relevance of the presence of TDs, lymph node metastases (LNMs), and extramural vascular invasion (EMVI) on the pattern of metastases and outcomes. Results Of 10,106 included patients with CRC, 22% presented with TDs. TDs are invariably associated with poor outcome. Presence of TDs was associated with presence of LNMs and EMVI. In a pairwise comparison, effects of TD were stronger than those of both LNMs and EMVI. In the logistic regression model, TDs in combination with LNMs is the strongest predictor for liver (odds ratio [OR], 5.5), lung (OR, 4.3) and peritoneal metastases (OR, 7.0). Presence of EMVI adds information for liver and lung metastases, but not for peritoneal metastases. Conclusion We have shown that TDs are not equal to LNMs or EMVI with respect to biology and outcome. We lose valuable prognostic information by allocating TDs into nodal category N1c and only considering TDs in the absence of LNMs. Therefore, we propose that the number of TDs should be added to the number of LNMs to derive a final N stage.
Coagulation Factor Thrombin Regulates Hematopoietic Stem and Progenitor Cell Egress and Mobilization Via PAR-1 &amp; CXCR4 Upregulation, SDF-1 Secretion and EPCR Shedding
Authors: Shiri Gur-Cohen, Tomer Itkin, Aya Ludin, Orit Kollet, Karin Golan, Alexander Kalinkovich, Elias Shezen, Tsvee Lapidot
Journal: Blood (2011)
Initial Results of US Intergroup Trial of Response-Adapted Chemotherapy or Chemotherapy/Radiation Therapy Based on PET for Non-Bulky Stage I and II Hodgkin Lymphoma (HL) (CALGB/Alliance 50604)
Authors: David J. Straus, Brandelyn Pitcher, Lale Kostakoglu, John C Grecula, Eric D. Hsi, Heiko Schoder, Sin-Ho Jung, Leslie L. Popplewell, Julie E Chang, Craig H Moskowitz, Nina Wagner-Johnson, John P. Leonard, Jonathan W. Friedberg, Brad S Kahl, Bruce D. Cheson, Nancy L. Bartlett
Journal: Blood (2015)
Leukemia-Reactive Cytotoxic CD8+ and CD4+ T-Cells Specific for Novel WT-1 Epitopes Are Generated In Vitro by Sensitization with Overlapping Pentadecapeptides (15-mers) Spanning the Wilms Tumor Protein.
Authors: Ekaterina Doubrovina, Jacob Dupont, Elena Kanaeva, Richard J. O’Reilly
Journal: Blood (2007)
Successful Allogeneic Hematopoietic Stem Cell Transplantation for Severe Inflammatory Bowel Disease – IL10 Receptor Deficiency May Serve as a Novel Therapeutic Paradigm
Authors: Rita Beier, Daniel Kotlarz, Kaan Boztug, Erik Glocker, Eva Doreen Pfister, Jana Diestelhorst, Dhaarini Murugan, Ulrich Baumann, Sibylle Koletzko, Axel Sauerbrey, Stephan Bruderus, Bodo Grimbacher, Martin G. Sauer, Karl-Walter Sykora, Christoph Klein
Journal: Blood (2010)
718. AAV-Mediated Local Anti-EGFR Antibody Gene Expression in CNS Delays Tumor Growth and Increases Survival in a Human Glioblastoma Xenograft Model
Authors: Maria J. Chiuchiolo, Martin J. Hicks, Yie Xie, Fan Fan, Jonathan B. Rosenberg, Jonathan P. Dyke, Kosuke Funato, David F. Havlicek, Douglas J. Ballon, Viviane Tabar, Dolan Sondhi, Stephen M. Kaminsky, Ronald G. Crystal
Journal: Molecular Therapy (2015)

Epidermal growth factor receptor (EGFR) is an attractive target for the treatment of glioblastoma (GBM), where deregulated expression or activity of EGFR has been associated to tumor development, progression and spread, and decreased survival. Systemic administration of an anti-EGFR antibody (CetuximabTM) reduces cellular proliferation in a variety of cancer models, but for GBM, efficacy is limited by the blood-brain barrier, where only ~ 0.1% of circulating antibodies reach the brain. To circumvent these limitations, we have developed a strategy to deliver the cDNA sequence for the anti-EGFR antibody directly to the CNS via adeno-associated virus (AAV) gene transfer vectors, resulting in local, persistent expression in the CNS. Efficacy of this therapeutic approach was evaluated by assessment of survival of NOD/SCID immunodeficient mice after CNS administration of human U87MG glioblastoma cells modified to express wild type EGFR to the striatum, either at the same time or 8 days prior to the administration of an AAVrh. 10-based vector coding for the anti-EGFR monoclonal antibody Cetuximab (AAVrh. 10CetMab). Localized expression of the antibody was confirmed by Western analysis and ELISA. Simultaneous administration of AAVrh. 10CetMab and GBM xenograft to the CNS was associated with survival of the treated animals compared to controls that received PBS (AAVrh. 10CetMab treated 5 ± days vs PBS-treated, 31±2 days, p<0.0001). Administration of the vector 8 days after tumor cells delivery, reduced tumor growth by 3-fold at 4 wk as measured by CNS MRI (p<0.05), and increased survival of the antibody treated mice (AAVrh. 10CetMab-treated 36±4 days vs PBS-treated, 3 ± days, p<0.02). Likewise, CNS administration of the AAVrh. 10CetMab vector 3 wk after mice received patient-derived early passage GBM primary cells to the CNS increased survival in the antibody-treated animals with respect to the controls (AAVrh. 10CetMab treated 98±3 days vs PBS-treated, 88±3 days, p<0.03). The data demonstrates that local delivery of an anti-EGFR antibody by an AAVrh. 10-derived vector reduced GBM tumor growth and increased survival in mice with a cell line expressing EGFR and patient-derived xenografts. AAV-mediated antibody gene transfer directly to the CNS may provide an effective treatment of glioblastoma, with therapeutic levels of antibody expression in the tumor milieu.
Abstract 1534: The microbiome of cancer as seen through the lens of public genome sequence data
Authors: Kelly M. Robinson, Karsten B. Sieber, Kathleen E. Anderson, David R. Riley, Julie C. Dunning Hotopp
Journal: Cancer Research (2015)

Abstract There are 10 times more bacterial cells in the human body than human cells and various bacteria are known to influence carcinogenesis. Therefore we sought to investigate if publicly available whole genome and whole transcriptome sequencing data generated by large public cancer genome efforts, like The Cancer Genome Atlas (TCGA), could be used to examine the microbial composition of tumors. The Burrows-Wheeler Aligner (BWA) was used to align a selection of Illumina paired-end sequencing data from TCGA data to the human reference genome and all complete bacterial genomes in the RefSeq database. Reads were filtered for low complexity and duplicates and then assigned an Operational Taxonomic Unit (OTU). Through careful consideration of all of the bacterial taxa present in the cancer types investigated, we found an increased abundance of Acinetobacter spp. in acute myeloid leukemia (AML) samples, Mycobacterium tuberculosis complex in ovarian serous cystadenocarcinomas (OV), and Pseudomonas spp. in stomach adenocarcinoma (STAD) samples. Further investigation prompted us to conclude that Mycobacterium tuberculosis complex read pairs were found in the OV samples due to sequencing center batch effects. The same analysis of the AML and STAD samples suggests that Acinetobacter spp. are truly present in AML samples and that Pseudomonas spp. are actually present in the STAD samples investigated. Upon completion of this analysis, we determined that it is possible to identify bacteria in human tumor samples. However, care must be taken to assess bacteria that arrived in the sample via various forms of contamination. It is also important to note that the sequencing library method heavily biases the bacterial taxa identified. One sample sequenced with RNA-Sequencing, whole exome sequencing (WXS), and whole genome sequencing (WGS) had extensively different bacteria reflected in the RNA-Seq data compared to that of WGS and WXS. In the future, a comprehensive approach should be used when evaluating the microbiome of tumor samples via sequencing data. The methods used in this study are valid and useful for identifying the presence of bacteria in human samples, but may not be an exhaustive picture. More weight should be given to this approach in the future when bacterial associations with diseases are suspected. Citation Format: Kelly M. Robinson, Karsten B. Sieber, Kathleen E. Anderson, David R. Riley, Julie C. Dunning Hotopp. The microbiome of cancer as seen through the lens of public genome sequence data. [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 1534. doi:10.1158/1538-7445.AM2015-1534
Hoxa9/Meis1 Mediate Leukemic Programming through Microrna-155
Authors: Edith Schneider, Anna Staffas, Milijana Mirkovic-Hoesle, Bernhard Gentner, Jens Ruschmann, Christian Buske, Michael Heuser, Konstanze Döhner, Hartmut Döhner, R. Keith Humphries, Arefeh Rouhi, Florian Kuchenbauer, Lars Palmqvist
Journal: Blood (2014)
Immortalized Human Placenta Derived Mesenchymal Cells by Transfection with Bmi-1 Lost the Abilitiy To Differencitate into Cell Types of Osteocytic, Condoricytic and Neural Lineages.
Authors: Xiaohong Zhang, Yasushi Soda, Kenji Takahashi, Yuansong Bai, Koichi Igura, Ayako Mitsuru, Arinobu Tojo, Tsuneo A. Takahashi
Journal: Blood (2004)
Abstract 4912: Screening of multiplex gene mutations using cell-free DNA in lung cancer patients
Authors: Nak-Jung Kwon, Jae Sook Sung, Ahreum Seong, Hyunmi Kim, Woo Chung Lee, Yeul Hong Kim, Kap-Seok Yang, Jeong-Sun Seo
Journal: Cancer Research (2015)

Abstract Cell free DNA present in the blood stream shows much potential as a useful cancer maker for early diagnosis and cancer progression monitoring. Especially, analyzing the cell free DNA with Next Generation Sequencing (NGS) technology allows high through put examination of various genes concurrently at a low cost. On average, healthy person's serum contains only about 5ng/ml of cell free DNA, whereas a cancer patient's serum contains up to 1,500ng/ml of cell free DNA. For these reasons, cell free DNA could be a useful cancer marker to further our understanding of the patient's conditions. However, sequencing cell free DNA using NGS platform requires various quality control steps to ensure the quality and the quantity of the cell free DNA extracted and the libraries produced from them. In this study, we examined the viability of using cell free DNA on NGS platforms. First, DNA was extracted and sequencing libraries were prepared using currently available commercial kits. Next, the quality of the libraries prepared was evaluated through whole genome sequencing on MiSeq. Lastly, lung cancer driver mutation was analyzed using TruSight Cancer Content Set and Ion AmpliSeq Cancer hotspot Panel. Two panels were chosen in order to study the viability of capture hybridization method and amplicon method. Citation Format: Nak-Jung Kwon, Jae Sook Sung, Ahreum Seong, Hyunmi Kim, Woo Chung Lee, Yeul Hong Kim, Kap-Seok Yang, Jeong-Sun Seo. Screening of multiplex gene mutations using cell-free DNA in lung cancer patients. [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 4912. doi:10.1158/1538-7445.AM2015-4912
423. The Combination of p53 Dendritic Cell Vaccine and Ad-p53 Gene Therapy Against p53 Overexpressing and p53 Deleted Tumor Cell Lines
Authors: Hiroki Saito, Koichi Kitagawa, Risa Yamasaki, Nami Katai, Naoya Morishita, Masato Kawabata, Dody Bautista, Dante Dator, Toshiro Shirakawa
Journal: Molecular Therapy (2015)

DC are the most potent antigen-presenting cells and stimulate the immune system to protect the host from infectious and cancerous diseases. Adaptive immune system, especially CTL response, is important for cancer treatment. DC take up tumor antigens through phagocytosis, macropinocytosis or endocytosis utilizing Fc receptors. Upon uptake, DC process protein antigens into peptides that are loaded onto MHC molecules for presentation to T cells and are able to induce T cell dependent immune responses. In this study, we induced the p53 specific CTL by co-culturing the p53 DC vaccine, and examined the antitumor effect of p53 specific CTL against the cancer cell lines expressing p53 protein, and the p53-deleted cancer cell line with or without Ad-p53 infection. DC were generated from the peripheral blood mononuclear cells (PBMC) which were isolated from a healthy volunteer, incubated in medium for 2 hours at 37°. Following 2 hours incubation, only adherent cells were incubated in medium with IL-4 and GM-CSF for 6 days to generate immature DC. To generate p53 DC vaccine, the immature DC were infected with Ad-p53 to present p53 peptides on the MHC molecules. Presenting p53 peptides on the cell surface were examined by flow cytometry. To generate CTL, PBMCs were isolated from the healthy volunteer, and incubated in medium for 24 hours at 37°. Only suspended cells and the p53 DC vaccine were co-cultured to differentiate into CTL cells in medium with IL-2 and IL-7 for 9 days. Thereafter, the lymphocyte phenotype was analyzed by flow cytometry. The cytotoxicities of CTL incubated with the p53 DC vaccine, control of CTL incubated with the DC infected with recombinant adenovirus encoding LacZ gene (Ad-LacZ), and naive CTL, against human cervical carcinoma cell line, which expresses p53, human prostate cancer cell line, which deleted p53 gene and PC-3 infected with Ad-p53 were investigated by the in vitro cytotoxicity assay. Ad-p53 infection significantly increased the rate of mature DC co-expressing p53 peptides and HLA-DR on the cell surface. The cytotoxicity of CTL incubated with the p53 DC vaccine against CaSki cells was significantly higher than that of naive CTL and CTL incubated with Ad-LacZ-DC. In addition, the cytotoxicity of the CTL incubated with the p53 DC vaccine against PC-3 cells was enhanced by Ad-p53 infection to PC-3 target cells. These results indicated that the p53 vaccine could differentiate naive CTL to the p53-specific CTL, and the p53 specific CTL showed the higher cytotoxicity against p53-overexpressing cancer cells and Ad-p53 infected cancer cells. This finding suggested that the strategy of p53 DC vaccine immunotherapy with intra-tumoral injection of Ad-p53 gene therapy has a great potential to create a new paradigm for cancer therapies.
Abstract 599: A panel of mass spectrometry based serum protein tests for predicting graft-versus-host disease (GvHD) and its severity
Authors: Heinrich Roder, Andreas-Claudius Hoffmann, Joanna Roder, Michael Koldehoff
Journal: Cancer Research (2015)

Abstract Allogeneic hematopoietic stem cell transplantation (AHSCT) has been shown to provide longterm disease-free survival for otherwise fatal malignant or nonmalignant hematological disorders. Acute and chronic graft-versus-host disease (aGvHD and cGvHD) are a major complication following AHSCT and are associated with a substantial morbidity and mortality. Identification of patients (pts) likely to develop severe forms of GvHD could allow the selection of more aggressive therapeutic regimens for patients assessed to be at high risk. Serum samples and clinical data were available from 124 pts (age 18-70) who had received AHSCT. Five pts suffered no GvHD, 15 de novo cGvHD, 21 aGvHD but no cGvHD and 83 both aGvHD and cGvHD (overlap). Of pts with aGvHD 51% had grade I disease and of pts with cGvHD 53% had limited disease. Matrix assisted laser desorption/ionization (MALDI) mass spectra were acquired from the samples using the deep MALDI method, allowing a deep probing of the proteome. Spectra were preprocessed and spectral features defined. The integrated intensities of these features were combined with the clinical data using deep learning based machine learning to create classifiers able to stratify patients into groups depending on occurrence and severity of GvHD. Classifiers could be developed with significant power to predict occurrence and severity of GvHD. The area under the curves (AUCs) obtained for the clinical questions investigated and examples of the sensitivity and specificity achievable are summarized in the table. AUCSensitivity/SensitivityaGvHD ?0.7463%/80% or 80%/65%Grade II or severe aGvHD?0.6560%/67%cGvHD post aGvHD?0.7563%/75%severe vs mild cGvHD?0.6867%/69% It is possible to provide information on occurrence and severity of GvHD from mass spectral analysis of post-transplant serum samples. If validated, this panel of tests could provide additional information useful for clinicians choosing treatment regimens for pts following AHSCT. Citation Format: Heinrich Roder, Andreas-Claudius Hoffmann, Joanna Roder, Michael Koldehoff. A panel of mass spectrometry based serum protein tests for predicting graft-versus-host disease (GvHD) and its severity. [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 599. doi:10.1158/1538-7445.AM2015-599
Introduction of clinical sequence using a comprehensive cancer gene panel (OncoPrime) to daily clinical practice
Authors: Masashi Kanai, Tomohiro Sakuma, Koji Yanagisawa, Tomoyoshi Koyanagi, Shigemi Matsumoto, Tomohiro Kuroda, Satoshi Morita, Shinji Kosugi, Yasushi Okuno
Journal: Annals of Oncology (2015)