tbuckley/cabot-search huggingface dataset:
New lesions versus growth of existing disease: Does it impact prognosis?
Authors: A. Grothey, J. M. Heun, M. Branda, R. M. Goldberg, D. J. Sargent
Journal: Journal of Clinical Oncology (2011)

2579 Background: Clinical trials use established criteria (RECIST or WHO) to determine objective tumor behavior on therapy. Participants are labeled to have progressive disease (PD) and are taken off study if they meet specific parameters of increase in size of their known lesions, but can also be labeled as PD if they develop new lesions without meeting criteria for progression in known lesions. To determine whether there are outcome disparities among these patients, we explored survival differences by reason of progression among patients who developed PD on study using data from the phase III Intergroup trial N9741 which compared IFL, FOLFOX4, and IROX as first-line therapy in advanced colorectal cancer (Goldberg JCO 2004). Methods: Patients who developed PD while receiving treatment on study were identified and reasons for progression were determined. Survival from time of progression was then compared among patients progressing due solely to the development of new lesions versus patients progressing for other causes (increase in known lesion size, clinical progression, ascites, pleural effusion, brain metastasis, or any combination of these). Results: 726 patients developed PD while receiving treatment on study. Reasons for progression could be identified in 703 patients who were then included in this analysis. Development of new lesions was the only reason for progression in 158 patients (22.5%). Patients with progression due solely to the development of new lesions did not differ in survival compared with patients progressing for all other causes (HR 1.01, p=0.92). These similarities remained despite controlling for length of treatment, treatment arm and performance status. Conclusions: In N9741, survival after development of new lesions as the sole reason for progression did not significantly differ from patients with other reasons of PD. These findings give further validation to the use of new lesions as a classifier of PD according to established criteria.
Incidence and Outcome of Non-CMV Viral Infections in 202 Consecutive Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) Recipients.
Authors: Christian Junghanss, Sebastian Rohde, Max Haversath, Guenther Kundt, Daniel Wolff, Inken Hilgendorf, Holger Andree, Jochen Casper, Malte Leithaeuser, Christoph Kahl, Mathias Freund
Journal: Blood (2007)
Nicotinamide Promotes Apoptosis In Chronic Lymphocytic Leukemia through Activation of the p53/Mir-34a/SIRT1 Tumor Suppressor Network
Authors: Valentina Audrito, Tiziana Vaisitti, Sara Serra, Davide Rossi, Daniela Gottardi, Giovanni D’Arena, Gianluca Gaidano, Fabio Malavasi, Silvia Deaglio
Journal: Blood (2010)
Abstract A63: Human pancreatic cells have distinct aspects in induction of acinar to ductal metaplasia
Authors: Jun Liu, Naoki Akanuma, Luzhe Sun, Pei Wang
Journal: Cancer Research (2016)

Abstract Multiple animal studies suggest that pancreatitis-induced acinar-to-ductal metaplasia (ADM) is a key event for the initiation of pancreatic ductal adenocarcinoma (PDAC) tumorigenesis. However, until now, there has not been an adequate system to explore the mechanisms of ADM induction in humans. To address this problem, we have developed a flow cytometry-based, high resolution lineage tracing method to analyse ADM in primary human cells. Using a set of cell surface markers, we have successfully defined and purified human acinar, ductal and acinar-to-ductal transdifferentiated (AD) cells. A Matrigel-based 3D culture system which suppresses spontaneous ADM was developed to identify ADM inducers of primary human acinar cells. In contrast to the effect in mouse acinar cells, TGF-β1 efficiently converted human acinar cells to AD cells in a SMAD-dependent manner. Consistently, phospho-SMAD3 (p-SMAD3) expression was significantly increased in acinar cells from human pancreatitis samples, supporting an important role of the TGF-β/SMAD axis for human ADM in vivo. Furthermore, all known inducers of ADM in mice did not promote ADM in human cells, highlighting fundamental differences between the species. Capitalizing on our ability to separate different cell populations for functional analysis, we found that AD cells gained transient proliferative capacity. More interestingly, while oncogenic KRAS did not induce acinar cell proliferation, it did sustain proliferation of AD cells, suggesting that oncogenic KRAS requires ADM-associated-changes to promote PDAC initiation. This ADM model provides a novel platform to explore the mechanisms involved in the development of human pancreatic diseases. Grant Support: Support received from the Cancer Prevention and Research Institute of Texas (P. Wang). Jun Liu received support by way of the training grant (RP140105) from the Cancer Prevention and Research Institute of Texas. Citation Format: Jun Liu, Naoki Akanuma, Luzhe Sun, Pei Wang.{Authors}. Human pancreatic cells have distinct aspects in induction of acinar to ductal metaplasia. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2016 May 12-15; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract nr A63.
Abstract 2261: DLGAP5, MAT1A, SKA3, and ZMYM5 are novel susceptibility genes for aggressive prostate cancer
Authors: Minnkyong Lee, Kendra A. Williams, Ying Hu, Jonathan Andreas, Shashankkumar J. Patel, Suiyuan Zhang, Nigel PS Crawford
Journal: Cancer Research (2015)

Abstract Prostate cancer is a common disease with approximately 233,000 men estimated to be diagnosed in the United States alone in 2014. Yet, it is usually an indolent disease with only 13% of patients succumbing to prostate cancer, and the molecular determinants of aggressive prostate cancer remain unclear. Previously, we reported that germline variation influences disease aggressiveness in the C57BL/6-Tg(TRAMP)8247Ng/J (TRAMP) mouse model. These mice develop neuroendocrine prostate tumors similar to a subset of human prostate tumors associated with poor outcomes. Here, we used a multifaceted approach to identify candidate genes for susceptibility to aggressive prostate tumorigenesis and metastasis using the TRAMP mouse model. Candidate prostate cancer metastasis susceptibility genes were identified through quantitative trait locus (QTL) mapping in 201 (TRAMP x PWK/PhJ) F2 males. Two aggressive disease QTLs were identified; one for lymph node metastasis burden on chromosome 12 (LOD = 5.86) and one for distant metastasis-free survival on chromosome 14 (LOD = 4.41). Correlation analysis using microarray data derived from 27 (TRAMP x PWK/PhJ) F2 prostate tumors identified 35 metastasis-associated transcripts within the two loci. The role of these genes in susceptibility to aggressive human prostate cancer was analyzed in two different datasets. First, logistic regression and survival analyses in human prostate cancer gene expression datasets demonstrated that the expression levels of 5 of the 35 candidate genes was associated with both an increased risk of aggressive disease and a poorer disease-free survival. Second, four of these genes - DLGAP5, MAT1A, SKA3, and ZMYM5 - harbored SNPs associated with aggressive tumorigenesis in the PLCO/CGEMS GWAS cohort of 1,172 prostate cancer patients. This approach, novel to the prostate cancer field, demonstrates how mouse models can be used to identify aggressive disease susceptibility genes, and gives new insight into the molecular mechanisms of aggressive disease. Citation Format: Minnkyong Lee, Kendra A. Williams, Ying Hu, Jonathan Andreas, Shashankkumar J. Patel, Suiyuan Zhang, Nigel PS Crawford. DLGAP5, MAT1A, SKA3, and ZMYM5 are novel susceptibility genes for aggressive prostate cancer. [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 2261. doi:10.1158/1538-7445.AM2015-2261
423. Clinical Translation of Immunovirotherapy: Measles Virus and Anti-PD1
Authors: Christine E. Engeland, Rūta Veinalde, Christof von Kalle, Dirk Jaeger, Guy Ungerechts
Journal: Molecular Therapy (2016)

After preclinical proof-of-concept that oncolytic virotherapy and immune checkpoint modulation have synergistic effects, we will conduct a phase I/II clinical trial combining a measles vaccine strain and an anti-PD1 antibody. Patients with hepatic metastases of pancreatic adenocarcinoma receive ultrasound-guided intralesional virus injections and systemic administration of anti-PD1. A main focus is the translational research program which accompanies the trial. In sequential biopsies we will quantify the type, density and distribution of immune effector cells. Cytokine and chemokine profiles of tumor and blood samples are analyzed to identify biomarkers predictive of response. Transcriptome and immunoreceptor sequencing are performed to predict neoepitopes and monitor T cell dynamics. This comprehensive data set will allow us to identify immune signatures associated with response and pinpoint mechanism of action in immunovirotherapy.
Abstract 3417: Snail and serpinA1 promote tumor progression and predict prognosis in colorectal cancer
Authors: Chae Hwa Kwon, Hye Ji Park, Ja Rang Lee, Hye Kyung Kim, Do Youn Park
Journal: Cancer Research (2015)

Abstract Purpose: Snail and serpin peptidase inhibitor clade A member 1 (serpinA1) are involved in tumor progression. In this study, we investigated the role of Snail and serpinA1 in colorectal cancer (CRC) and examined the mechanisms through which these proteins mediate CRC progression. Experimental Design: Tumors from 528 patients with CRC were examined to determine the clinicopathological significance of Snail and serpinA1 expression. Cell migration and invasion were assessed to determine the functional roles of Snail and serpinA1. Snail binding to the serpinA1 promoter was analyzed by chromatin immunoprecipitation (ChIP) assays. Results: Immunohistochemical analysis of 528 samples from patients with CRC showed that elevated expression of Snail or serpinA1 was correlated with advanced stage, lymph node metastasis, and poor prognosis. Moreover, we detected a correlation between Snail and serpinA1 expression. Functional studies performed using the CRC cell lines DLD-1 and SW-480 showed that overexpression of Snail or serpinA1 significantly increased CRC cell invasion and migration. Conversely, knockdown of Snail or serpinA1 expression suppressed CRC cell invasion and migration. ChIP analysis revealed that Snail regulated serpinA1 by binding to its promoter. In addition, fibronectin mediated Snail and serpinA1 signaling and was involved in CRC cell invasion and migration. Conclusion: Taken together, our data showed that Snail and serpinA1 promoted CRC progression through fibronectin. These findings suggested that Snail and serpinA1 were novel prognostic biomarkers and candidate therapeutic targets in CRC. Note: This abstract was not presented at the meeting. Citation Format: Chae Hwa Kwon, Hye Ji Park, Ja Rang Lee, Hye Kyung Kim, Do Youn Park. Snail and serpinA1 promote tumor progression and predict prognosis in colorectal cancer. [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 3417. doi:10.1158/1538-7445.AM2015-3417
Abstract LB-161: Frequent somatic transfer of mitochondrial DNA into the nuclear genome of human cancer cells
Authors: Young Seok Ju, Jose Tubio, William Mifsud, Beiyuan Fu, Fengtang Yang, Peter Campbell, Michael Stratton
Journal: Cancer Research (2015)

Abstract Mitochondrial genomes are separated from the nuclear genome for most of the cell cycle by the nuclear double membrane, intervening cytoplasm and the mitochondrial double membrane. Despite these physical barriers we show that somatically acquired mitochondrial-nuclear genome fusion sequences are present in cancer cells. Most occur in conjunction with intranuclear genomic rearrangements and the features of the fusion fragments indicate that non-homologous end joining and/or replication-dependent DNA double strand break repair are the dominant mechanism involved. Remarkably, mitochondrial-nuclear genome fusions occur at a similar rate per base pair of DNA as interchromosomal nuclear rearrangements, indicating the presence of a high frequency of contact between mitochondrial and nuclear DNA in some somatic cells. Transmission of mitochondrial DNA to the nuclear genome occurs in neoplastically transformed cells, but we do not exclude the possibility that some mitochondrial-nuclear DNA fusions observed in cancer occurred years earlier in normal somatic cells. Citation Format: Young Seok Ju, Jose Tubio, William Mifsud, Beiyuan Fu, ICGC Prostate Cancer, Bone Cancer, Breast Cancer Working Groups, Fengtang Yang, Peter Campbell, Michael Stratton. Frequent somatic transfer of mitochondrial DNA into the nuclear genome of human 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-161. doi:10.1158/1538-7445.AM2015-LB-161
Outcome following resection for patients with primary mediastinal nonseminomatous germ cell tumors and rising serum tumor markers post-chemotherapy
Authors: S. M. Radaideh, V. Cook, K. A. Kesler, L. H. Einhorn
Journal: Journal of Clinical Oncology (2008)

5038 Background: Primary mediastinal non-seminomatous germ cell tumors (PMNSGT) have been categorized as poor risk disease. They are rarely curable with salvage chemotherapy. Our institution has subscribed to a policy of surgically removing any residual disease if deemed resectable after cisplatin-based chemotherapy regardless of serum tumor marker (STM) status. In this study, we retrospectively analyzed outcomes of patients who presented to surgery with rising alphafetoprotein (AFP) or human chorionic gonadotropin (hCG). Methods: All patients with PMNSGT who received platinum based chemotherapy followed by complete surgical extirpation of residual disease at Indiana University between1981–2007 were retrospectively reviewed. Univariate comparisons were performed for multiple variables including STM at time of diagnosis and surgery, presence of lung metastasis, extrathoracic disease, sites of relapse, and outcomes in the subset of patients with rising STM after chemotherapy. Results: Of 158 patients (155 males and 3 females) who underwent post-chemotherapy surgery, 36 patients (35 males and 1 female) had rising STM after chemotherapy. The median age of this subset was 27 (range 19–44). Three patients had rising hCG (21, 92, 1,500 mU/ml), one had rising AFP and hCG (58 mU/ml), and the remaining 32 had rising AFP at the time of surgery, with median AFP 159.5 ng/ml (range 29–8,445). Despite the presence of rising markers post-chemotherapy, 8 patients pathologically demonstrated teratoma and 3 patients necrosis only at time of resection. Thirty patients normalized their tumor markers postoperatively. Twenty-one of 36 died (including three postoperative deaths), five were lost to follow-up, and ten are alive. Of the ten patients alive, 8 are continuously disease-free with median follow up of 73 months (range 4–220). Seven of these 8 patients had germ cell cancer pathologically demonstrated in resected mediastinal mass and 2 in resected lung metastases. Conclusions: Rising markers post-chemotherapy in patients with PMNSGCT connote a poor prognosis. However, selected pts may still be curable with extensive resection by experienced thoracic surgical oncologists No significant financial relationships to disclose.
Abstract 5019: Characterization of sentinel node-derived antibodies from breast cancer patients
Authors: Girja S. Shukla, Stephanie C. Pero, Yu-Jing Sun, Chelsea L. Carman, David N. Krag
Journal: Cancer Research (2015)

Abstract Lymph nodes are one of the important sites in the body where immune responses to antigens are initiated. The tumor-draining lymph node or sentinel node is the first site where cancer cells and cancer-related antigens are most likely to spread. In response to antigen exposure and immune activation, the lymph node B cells undergo clonal expansion and somatic hypermutation, leading to the affinity-matured populations of effector B cells secreting antibodies that bind to the tumor. The cancer-draining node is therefore an ideal source of B cells that produce anticancer antibodies. In the present investigation, we have characterized the antibodies derived from immortalization of sentinel node B cells from 29 breast cancer patients. The antibodies were screened for their isotypes and for binding to breast cancers classified as luminal A, luminal B, HER2, and basal/normal subtypes, based on the expressions of estrogen, progesterone and HER2 receptors. The isotype analysis showed a higher percentages of antibodies belong to IgG (48%) and IgM (34%) isotypes along with a smaller share of IgA (18%). The cell-binding studies were conducted using ELISA, immunofluorescence microscopy, and flow cytometry techniques. Of the studied antibodies, about 28% showed binding to the tumor cells. The comparative studies of antibody-binding to breast tumor cells and non-cancer breast cells identified several antibodies showing differential binding profile. The binding analyses also demonstrated that all of the tumor-binding antibodies belonged to IgM isotype. It is evident from the results that the tumor-reactive antibodies are generated in the sentinel nodes of breast cancer patients; however, the absence of class-switched anti-tumor antibodies in the repertoire raises a possibility of tumor-induced node suppression leading to an inefficient humoral immune response towards tumor antigens. The results are important in assessing the tumor immune response/lymph node suppression, and the possible role of the autoantibodies in diagnosis and therapy of breast cancer. Citation Format: Girja S. Shukla, Stephanie C. Pero, Yu-Jing Sun, Chelsea L. Carman, David N. Krag. Characterization of sentinel node-derived antibodies from breast 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 5019. doi:10.1158/1538-7445.AM2015-5019
Abstract 1640: Exploiting the cytoskeletal filaments of neoplastic cells to potentiate a novel therapeutic approach
Authors: Matthew Trendowski
Journal: Cancer Research (2015)

Abstract Although cytoskeletal-directed agents have been a mainstay in chemotherapeutic protocols due to their ability to readily interfere with the rapid mitotic progression of neoplastic cells, they are all microtubule-based drugs, and there has yet to be any microfilament- or intermediate filament-directed agents approved for clinical use. There are many inherent differences between the cytoskeletal networks of malignant and normal cells, providing an ideal target to attain preferential damage. Further, numerous microfilament-directed agents, and an intermediate filament-directed agent of particular interest (withaferin A) have demonstrated in vitro and in vivo efficacy, suggesting that cytoskeletal filaments may be exploited to supplement chemotherapeutic approaches currently used in the clinical setting. Therefore, this talk is intended to expose academics and clinicians to the tremendous variety of cytoskeletal filament-directed agents that are currently available for further chemotherapeutic evaluation. The mechanisms by which microfilament directed- and intermediate filament-directed agents damage malignant cells will be discussed in detail in order to establish how the drugs can be used in combination with each other, or with currently approved chemotherapeutic agents to generate a substantial synergistic attack, potentially establishing a new paradigm of chemotherapeutic agents. Note: This abstract was not presented at the meeting. Citation Format: Matthew Trendowski. Exploiting the cytoskeletal filaments of neoplastic cells to potentiate a novel therapeutic approach. [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 1640. doi:10.1158/1538-7445.AM2015-1640
Contributions of Phosphatidylserine Exposure on Leukemic Cells to Unregulated Procoagulant Activity in Acute Promyelocytic Leukemia.
Authors: Jin Zhou, Fenglin Cao, Chengfang Lu, Jinmei Li, Jinxiao Hou, Hongjuan Yu, Ming Ma, Shuchuan Liu, Jialan Shi
Journal: Blood (2007)
Epidemiology of Group-A β-Hemolytic Streptococci as Related to Acute Rheumatic Fever in Miami, Florida
Authors: MILTON S. SASLAW, JAMES M. JABLON, Madelyn Saul, Sallie Anne Jenks
Journal: Circulation (1960)

Rheumatic fever and rheumatic heart disease are infrequent in Dade County, Florida. Conversely, β-hemolytic streptococci are recovered frequently, particularly from the throats of children 6 to 9 years old. The relationship between group-A β-hemolytic streptococci, clinical illness, and rheumatic illness may be different in South Florida from elsewhere in the United States.
Prolylcarboxypeptidase Deficiency Is a Risk Factor for Arterial Thrombosis and Hypertension
Authors: Gregory Adams, Gretchen LaRusch, Evi Stavrou, Yihua Zhou, Marvin T. Nieman, Gretta Jacobs, Yingjie Cui, Yuan Lu, Mukesh K Jain, Fakhri Mahdi, Zia Shariat-Madar, Louis G D'Alecy, Alvin H. Schmaier
Journal: Blood (2010)
Interim Buprenorphine vs. Waiting List for Opioid Dependence
Authors: Stacey C Sigmon, Taylor A Ochalek, Andrew C Meyer, Bryce Hruska, Sarah H Heil, Gary J Badger, Gail Rose, John R Brooklyn, Robert P Schwartz, Brent A Moore, Stephen T Higgins
Journal: New England Journal of Medicine (2016)

In 50 opioid users on a waiting list for maintenance treatment, those assigned to interim treatment with buprenorphine submitted a higher percentage of urine specimens that were negative for illicit opioids than those in the control group at 4 weeks (88% vs. 0%), 8 weeks (84% vs. 0%), and 12 weeks (68% vs. 0%).
Uptake and Outcome of Artificial Reproductive Techniques Following Allogeneic Stem Cell Tranplantation: A Single Centre Experience.
Authors: Anna Babb, Nadine Farah, Jane Apperley, John Goldman, Edward Kanfer, David Marin, Dragana Milojkovic, Amin Rahemtulla, Katy Rezvani, Nina Salooja
Journal: Blood (2009)