tbuckley/cabot-search huggingface dataset:
Prognostic value of intratumoral tissue inhibitor of matrix metalloproteinase-1 in patients with gastric cancer-prospective follow up results-
Authors: T. Yoshikawa, S. Morinaga, Y. Noguchi, Y. Yamamoto, A. Tsuburaya, O. Kobayashi, M. Sairenji, H. Motohashi
Journal: Journal of Clinical Oncology (2004)

9644 Background: Intratumoral concentration of tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) has been reported to be related to disease progression in patients with gastric cancer, however, prognostic significance of tumor TIMP-1 concentrations has not been clarified. Methods: Concentrations of TIMP-1 protein were measured by enzyme-linked immuno-sorbent assay in tumor samples of 86 patients who underwent gastric resection and were followed-up prospectively for 5 years. Tumor TIMP-1 concentrations≥10.0 ng/mg protein were considered positive.Results: Positive tumor TIMP-1 was observed in 31 of 86 patients (36.0%). Kaplan-Meier survival curves were significantly different between patients with positive and those with negative tumor TIMP-1. By univariate analyses of the factors affecting survival, the depth of tumor invasion in the gastric wall (T), the extent of lymph node metastasis (N), the presence of peritoneal dissemination, lymphatic invasion, venous invasion, Lauren classification of histology, and tumor TIMP-1were found to be significant. By step-wise multivariate analysis, T, N, peritoneal dissemination, and tumor TIMP-1 remained independent prognostic factor, although the statistics for T, N, and tumor TIMP-1 did not reach significance. Conclusions: Tumor TIMP-1 seemed to be one of significant prognosticator for the survival in patients with gastric cancer. No significant financial relationships to disclose.
A Novel Role for CpG Oligonucleotides in Tumor Immunotherapy: CpG-ODN Induce Targeted Chemokine-Induced Lymphocyte Migration to the Peripheral Tissues in Humans.
Authors: W. Nicholas Haining, Holger Kanzler, Jeffrey Davies, Linda Drury, Jeffrey Kutok, Thomas Brenn, Jill Angelosanto, John Evans, Kate Russell, Stephen Rivoli, Suzanne George, Thomas Morgan, Xiaochun Li, Robert Coffman, Patrick Wen, George Demetri, Lee Nadler
Journal: Blood (2007)
Abstract 5593: Cigarette smoke and therapeutic response to chemotherapy and radiotherapy in cancer cells
Authors: Graham W. Warren, Michelle Romano, Samantha Sobus, Sundaravadivel Balasubramanian
Journal: Cancer Research (2015)

Abstract Background: The 2014 Surgeon General's Report concludes that cigarette smoke (CS) causes increased cancer specific mortality. Clinical data support that the effects of CS are reversible, but there are no extant biologic models that have shown therapeutic response profiles for cancer cells exposed to CS. Methods: An acute, subacute, and chronic dose escalated CS exposure model was developed to test the hypothesis that CS decreases therapeutic response to chemotherapy (CT, cisplatin) and radiotherapy (RT, 0, 2, 4, and 6 Gy) in a reversible manner in cancer cells. Results: H460, A549, and FaDu cancer cells were treated with single and multiple exposure CS for up to 12 weeks. Subacute and prolonged exposure to CS significantly decreased response to CT and RT. CS increased survival fraction following CT or RT between 30-157% across all cell lines. Exposure of cancer cells to CS for 6 or 9 weeks followed by removal of CS for 3 and 6 weeks resulted in a partial to complete restoration of baseline therapeutic response in a cell specific manner; however, all cell lines required several weeks to achieve a partial or full restoration of therapeutic response. Dose response curves for CS exposure demonstrate that H460 and A549 cells had a decreased therapeutic response profile at higher CS concentrations while FaDu cells were more sensitive to lower concentrations to CS. Dose response curves further demonstrated that high dose CS exposure was cytotoxic in all cell lines. Results were verified in all cell lines using 2 additional repeated experiments with freshly thawed cancer cells purchased from ATCC over 10 months. Conclusions: CS exposure reproducibly decreases therapeutic response to CT and RT in a dose dependent and reversible manner, reflective of clinical observations. Dose specific effects may vary between cancer cells. Data suggest that the biologic effects of CS removal, such as with acute smoking cessation in cancer patients, may not manifest in an immediate restoration of cancer cell response to CT or RT. Citation Format: Graham W. Warren, Michelle Romano, Samantha Sobus, Sundaravadivel Balasubramanian. Cigarette smoke and therapeutic response to chemotherapy and radiotherapy in 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 5593. doi:10.1158/1538-7445.AM2015-5593
A phase IIa clinical biomarker trial of aspirin and dietary arginine restriction in colorectal cancer patients.
Authors: J. A. Zell, C. E. McLaren, C. G. Albers, E. W. Gerner, L. B. Wenzel, F. L. Meyskens
Journal: Journal of Clinical Oncology (2011)

TPS132 Background: Colorectal cancer (CRC) patients are at high risk for recurrence and for secondary CRC development. Our preliminary findings provide a rationale for reducing tissue polyamines as tertiary chemoprevention in local and locally-advanced CRC patients. We will attempt to demonstrate rectal tissue putrescine reduction in stage I-III, optimally-treated CRC patients after treatment with dietary arginine restriction + daily oral aspirin in a phase IIa clinical biomarker trial. Methods: 24 participants will be treated with aspirin and an individualized dietary regimen to reduce arginine intake by >30% during the 12-week intervention. Sample size calculations were based on the Binomial test for a single proportion, to yield 80% Power. Six patients will receive psychosocial telephone counseling (PTC). Endoscopy with serial biopsies, phlebotomy, and urine collection will be performed pre- and post-intervention to assess potential biomarkers. The primary endpoint is a > 50% decrease in rectal tissue putrescine levels from baseline, as a measure of polyamine reduction in the target tissue of CRC patients. Secondary aims include: to demonstrate significant alterations in secondary endpoint biomarkers relevant to polyamine metabolism in CRC patients, including rectal mucosa Odc1 and Ssat expression and urinary polyamine metabolites; to determine this intervention’s side-effect profile in a population of optimally-treated CRC patients; to determine the efficacy of accrual to this novel type of clinical trial involving dietary intervention and oral aspirin therapy among a group of potentially cured cancer patients for whom there is currently no recommended further therapy; to assess feasibility of PTC and collect pilot data regarding the influence of PTC on compliance with the dietary prescription and compliance with aspirin, and if PTC further influences healthy exercise, reduced fatigue and improved quality of life when compared to the non-counseled cohort. Hypothesis: Among optimally-treated stage I-III CRC patients, a 12-week intervention of daily aspirin and a low-meat, arginine-restricted diet will favorably alter polyamine-related tissue, serum, and urinary biomarker levels.
The Bcl-2 Family Inhibitor ABT-263 Shows Significant Anti-Tumor Efficacy in Models of B Cell Non-Hodgkin’s Lymphoma.
Authors: Alex R. Shoemaker, Michael J. Mitten, Anatol Oleksijew, Jacqeuline M. O’Connor, Baole Wang, Scott Ackler, Mary Joseph, Haichao Zhang, Paul Nimmer, Yu Xiao, Christin Tse, David J. Frost, Stephen W. Fesik, Saul H. Rosenberg, Steven W. Elmore
Journal: Blood (2006)
KDE Analysis in Chronic Lymphocytic Leukemia Patients with B Cells Expressing IGHV3-21 and Discordant Mutational Status between Heavy and Light Chain.
Authors: Emanuela M. Ghia, Laura Z. Rassenti, George F. Widhopf, Gregg J. Silverman, Andrew W. Greaves, Thomas J. Kipps
Journal: Blood (2007)
Safety and Efficacy of Pomalidomide Plus Low-Dose Dexamethasone (POM + LoDEX) in Patients (Pts) with Relapsed/Refractory Multiple Myeloma (RRMM) in Italy: A Subanalysis of the Stratus Trial (MM-010)
Authors: Michele Cavo, Paolo Corradini, Francesco Di Raimondo, Mario Petrini, Anna Maria Cafro, Tommaso Caravita di Toritto, Massimo Offidani, Gianpietro Semenzato, Renato Zambello, Antonio Lazzaro, Maria Teresa Petrucci, Francesco Rodeghiero, Mathew Simcock, Ana Slaughter, Jennifer Herring, Teresa Peluso, Antonio Palumbo
Journal: Blood (2015)
725. Assessment of CSF Route for Gene Delivery in Sandhoff Mice Using AAV9 Expressing an Hexosaminidase Isoenzyme
Authors: Patrick Thompson, Karlaina Osmon, Evan Woodley, Subha Karumuthil-Melethil, Steven J. Gray, Jagdeep S. Walia
Journal: Molecular Therapy (2016)

GM2 gangliosidoses are a group of neurodegenerative disorders, characterized by the malfunctioning Hexosaminidase A (HexA) enzyme. HexA is formed by heterodimerization of two subunits, α and β. Hex A, in interaction with GM2 activator protein (GM2AP), is the main isoenzyme able to hydrolyze GM2 gangliosides. HexA deficiencies result in Tay-Sachs (α-subunit deficiency) or Sandhoff disease (SD, β-subunit deficiency). In the recent work by Tropak et al. (Mol Ther Methods Clin Dev, in press), a hybrid human α-subunit, named "µ" and coded by HEXM, was created (patent pending) by incorporating the dimer stabilization and GM2AP binding sites of the β-subunit while maintaining the catalytic properties of the α-subunit. The µ-subunit is able to homodimerize to form a stable and functional enzyme, named HexM, which can interact with the human GM2AP and effectively hydrolyse GM2 gangliosides. Another advantage of this subunit (~1.6 kb) is that it can be packaged in a self-complementary adeno-associated virus (scAAV/HEXM). An intravenous route of scAAV administration has been shown to be successful, but brings with it translational issues including large scale viral preparation and relatively high vector uptake by liver. We tested the cerebrospinal fluid (CSF) route, as an alternative, for delivering scAAV9/HEXM. We injected 2.5E+11 vector genomes per mouse of scAAV9/HEXM via the cisterna magna at 6 weeks of age (n=13). Our controls include treatment with scAAV9/GFP (n=3) and vehicle (n=8). One additional cohort received an IV injection of 25% mannitol (2g/kg) post-AAV9 injection (n=10). We sacrificed part of the cohorts (n=4 each group) at 16 weeks of age (humane end-point of untreated SD mice) for tissue analysis. The remainder are being monitored for long-term survival. The parameters for analyses are survival benefit, locomotor behaviour, Hexosaminidase activity, GM2 ganglioside accumulation, and vector genome biodistribution. The preliminary results from this ongoing study show a significant survival advantage to the humane endpoint in HexM treated (average 28 weeks to date) as compared to negative controls (~16 weeks). The behaviour tests showed improved locomotor activity in HexM-treated mice as compared to negative controls. Results were similar when mannitol was administered in conjunction with scAAV9/HEXM. These preliminary results indicate that the intra-CSF route of administration of AAV9/HEXM is a tractable translatable approach for SD worth further exploration. Additional studies are focused on increased dosage and methods to improve distribution.
Natural History of 33 Patients with Upshaw-Schulman Syndrome Has Revealed That All the Gravida Develop Thrombocytopenia, Often Followed by Thrombotic Microangiopathy with Stillbirth.
Authors: Yoshihiro Fujimura, Masanori Matsumoto, Koichi Kokame, Hideo Yagi, Ayami Isonishi, Tomomi Matsuyama, Seiji Kato, Hiromichi Ishizashi, Yasuaki Shida, Nishio Kenji, Nobu Akiyama, Junji Tomiyama, Kazuhiro Natori, Yasunobu Kuraishi, Yutaka Imamura, Nobumasa Inoue, Satoshi Higasa, Masako Seike, Teruhiko Kozuka, Masamichi Hara, Mitsuhiko Sugimoto, Hideo Wada, Mitsuru Murata, Toshiyuki Miyata, Yasuo Ikeda
Journal: Blood (2007)
Abstract 4065: Delineating the role of epithelial-mesenchymal transition in the generation and maintenance of prostate cancer stem cells
Authors: Anurag N. Paranjape, Rama Soundararajan, Steven J. Werden, Robiya Joseph, Joseph H. Taube, Neeraja Bhangre, Hui Liu, Jaime Rodriguez-Canales, Ignacio I. Wistuba, Jeffrey T. Chang, Dean G. Tang, Nupam Mahajan, Kiran Mahajan, Naoyuki Miura, Sendurai A. Mani
Journal: Cancer Research (2015)

Abstract Prostate cancer cells depend on androgens for growth and survival. While androgen-deprivation-therapy (ADT) results in regression of the tumor bulk, in many cases, the cancers recur in aggressive androgen-independent forms that are also resistant to standard-of-care therapies. The prevailing hypothesis is that pre-existing androgen-independent prostate cancer (PCa) stem-cells in the primary tumor are selectively enriched following therapy. However, we have previously shown that induction of epithelial-mesenchymal-transition (EMT) in differentiated breast epithelial cells can result in the generation of cells with stem-cell properties. In the current study, we investigated if induction of EMT in PCa promotes stem-cell features and androgen-receptor (AR) regulation, and if targeting EMT-promoting pathways renders PCa stem-cells sensitive to ADT. We found that LNCaP-PSAlow cells, which were previously shown to represent the PCa stem-cell population, exhibit EMT properties. Induction of EMT through over-expression of EMT-inducing transcription factors or with TGFβ1 treatment, significantly stimulated stem-cell properties in the androgen-sensitive LNCaP cells, whereas inhibition of EMT in the androgen-insensitive DU145 cells using targeted shRNA or a specific TGFβ1-signaling inhibitor, resulted in markedly reduced stemness. We observed that FOXC2 expression consistently correlated with induction of EMT and androgen-insensitivity in PCa cells. Our study demonstrates that targeting EMT-inducing molecules and signaling pathways could represent a tangible approach to inhibiting the generation and maintenance of therapy-resistant PCa stem-cells, that are the prime harbingers of tumor recurrence. Citation Format: Anurag N. Paranjape, Rama Soundararajan, Steven J. Werden, Robiya Joseph, Joseph H. Taube, Neeraja Bhangre, Hui Liu, Jaime Rodriguez-Canales, Ignacio I. Wistuba, Jeffrey T. Chang, Dean G. Tang, Nupam Mahajan, Kiran Mahajan, Naoyuki Miura, Sendurai A. Mani. Delineating the role of epithelial-mesenchymal transition in the generation and maintenance of prostate cancer stem 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 4065. doi:10.1158/1538-7445.AM2015-4065
PTU-039 Incidence of ulcerative colitis still rising in Cardiff (1988–2007): Abstract PTU-039
Authors: A V Ramadas, C Gwinnutt, G Thomas, G T Williams, A B Hawthorne
Journal: Gut (2010)

<h3>Introduction</h3> The incidence of UC in Cardiff has been reported previously between 1968–87. 12 The incidence of ulcerative colitis is generally regarded as having changed little for some time although some studies have reported increases and reductions over time. <h3>Methods</h3> To report the incidence of UC and indeterminate colitis (IC) in Cardiff between 1988–2007. Pathology database was searched for patients with UC and IC using the following SNOMED codes: colon, inflammation and UC. The patients were included in the incidence study if there was definite histological diagnosis of UC along with corroborative endoscopic findings as described by Lennard-Jones3 and were Cardiff residents at diagnosis (1988–2007). Patients were categorised as IC if they had features of IBD but no definitive diagnosis of either UC or CD on histology. <h3>Results</h3> 8340 pathology reports were reviewed and 453 UC and 51 IC patients were identified between 1988–2007. Incidence rates were age and sex corrected to England and Wales population of 2001. Population of Cardiff was 293 600 in 1991 and 305 353 in 2001. 206 UC cases identified in 1988–1997 (corrected incidence=7.01 cases/100 000, 95% CI 6 to 8) and 247 cases between 1998–2007 (corrected incidence=7.96 cases/ 100 000, 95% CI 7 to 9). M: F ratio was 1.2:1 and median age at diagnosis was 35.5 (1988–1997) and 34 (1998–2007). Disease distribution at diagnosis was proctitis (35%), distal colitis (38%) and total colitis (27%) in the entire cohort. Percentage of UC patients were smokers at diagnosis. The corrected incidence of IC for 1988–1997 was 0.94 cases/100 000 (95% CI 0.5 to 1.5) and 0.71 cases/100 000 (95% CI 0.5 to 1.5) for 1998–2007. The comparative crude incidence rates for UC for the period 1968–2007 are shown in Abstract 039. <h3>Conclusion</h3> This study shows the incidence of UC is rising in Cardiff in parallel with a small increase in Crohns incidence4 and there is a small decrease in IC incidence rate. Also the incidence of Crohns in Cardiff has shown a small increase.
Abstract 2511: Therapeutic dendritic cell targeting MIP3α-gp100 DNA vaccination with immunomodulatory αIL-10 and αPD-1 antibodies significantly enhances survival in a mouse melanoma model system
Authors: James Gordy, Richard B. Markham
Journal: Cancer Research (2015)

Abstract The current study demonstrates that the combination of a DNA vaccine encoding the chemokine MIP-3α fused to melanoma antigen gp100 with immunomodulatory antibodies prolongs survival in a melanoma mouse model. The current studies utilize the B16F10 mouse spontaneous melanoma syngeneic transplantable mouse model system. Previous published work with this vaccine platform has indicated the MIP-3α component targets nascent peptides to immature dendritic cells leading to processing by class I and class II MHC pathways. It has further been shown in this tumor system that prophylactic vaccination with the DNA construct alone delayed tumor growth. Other studies have provided evidence that αPD-1 or αIL-10 neutralizing antibodies enhance immunological melanoma therapies by modulating the tolerogenic tumor microenvironment. First, this study expanded previous results by finding a significant decrease in tumor burden and increase in survival by prophylactic intramuscular electroporation [IM EP] of the DNA vaccine construct. Adding three therapeutic doses of αIL-10 given subcutaneously [subQ] at the tumor site to the treatment further increased mouse survival. The development of cell-mediated and humoral immune responses were documented for the first time in this system by Elispot and in-cell ELISA assays. Secondly, a novel therapeutic vaccination protocol was developed by initiating vaccination and antibody therapies after tumor challenge. With this therapeutic protocol, we demonstrated for the first time that vaccine significantly delays tumor burden and increases median survival from 17 to 21 days (p = 0.006). Addition of αIL-10 (subQ) and αPD-1 (intra-peritoneally) antibodies led to further highly significant decreases in tumor burden and increased median survival from 17 to 25 days (p = 0.0005). Efficient targeting of antigen to immature dendritic cells with a chemokine fusion vaccine offers a potential alternative approach to the ex vivo dendritic cell antigen loading protocols currently undergoing clinical investigation. Combining this approach with agents able to modulate the tolerogenic tumor microenvironment offers promise as a novel melanoma therapy. Citation Format: James Gordy, Richard B. Markham. Therapeutic dendritic cell targeting MIP3α-gp100 DNA vaccination with immunomodulatory αIL-10 and αPD-1 antibodies significantly enhances survival in a mouse melanoma model system. [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 2511. doi:10.1158/1538-7445.AM2015-2511
Engraftment Patterns in NOD.SCID Mice Predict Outcome in Human AML
Authors: James A. Kennedy, Amanda Mitchell, Weihsu Claire Chen, Liqing Jin, Stanley Wai-Kwong Ng, Liran I. Shlush, Sasan Zandi, Jessica McLeod, Andreea C. Popescu, Nathan Mbong, Andrea Arruda, Mark D Minden, John E. Dick, Jean C.Y. Wang
Journal: Blood (2014)
Significance of a Critical Set of 11q Chromosome Aberrations for Diagnosis of MYC Negative Burkitt Lymphoma
Authors: Grzegorz Rymkiewicz, Magdalena Chechlinska, Beata Grygalewicz, Barbara Pienkowska-Grela, Katarzyna Blachnio, Zbigniew Bystydzienski, Joanna Romejko-Jarosinska, Beata Sledz-Gawronska, Michalina Zajdel, Katarzyna Domanska-Czyz, Renata Woroniecka, Kinga Sikorska-Mali, Jan Konrad Siwicki, Monika Prochorec-Sobieszek, Jan Walewski
Journal: Blood (2015)
Intra-arterial chemotherapy for local invasive bladder cancer.
Authors: F. Hongo, K. Mikami, T. Nakanouchi, Y. Naya, Y. Itoh, T. Nakamura, N. Takaha, T. Miki
Journal: Journal of Clinical Oncology (2011)

e15063 Background: We assessed the effectiveness of intra-arterial chemotherapy or a combination of intra-arterial chemotherapy and external beam radiation therapy. Methods: Between 1993- 2007, 73 patients with muscle invasive bladder cancer (stage T2-4N0M0) were treated with intra-arterial chemotherapy (53 cases) or a combination of intra-arterial chemotherapy and low dose external beam radiation therapy (20 cases). Low dose radiation therapy was given at dose of 2 Gy x 5 days. 53 cases were treated with 50 or 70/m2 of cisplatin (CDDP) and 20mg/m2 of doxorubicin (ADM) intra arterially. Median 3 courses (range 2-6 course) of therapy were performed. Each course of therapy was repeated every 4 weeks. 20 cases were treated with intra-arterial chemotherapy and low dose external beam radiation therapy. Radical cystectomy was required for 15 patients. Median follow up was 29 months (range 4-180 months). Results: CR was achieved in 38% (28) of patients. PR was 44% (32) of patients. Five- and ten-year over all survival rates were 60% and 54%. 53% (39) of patients survive with preserving their bladder. 21% died of cancer. The regimen was well tolerated, with no severe systemic or local toxicities. Conclusions: These findings suggest that Intra-arterial chemotherapy is a reasonable option for patients seeking an alternative to radical cystectomy.
Abstract 2089: Role of Cdx2 in maintainining differentiated chromatin structure during tumor progression
Authors: Ansu O. Perekatt, Ritu Rana, Namit Kumar, Michael Valdez, Michael Verzi
Journal: Cancer Research (2015)

Abstract Tumor progression often coincides with the appearance of tumor cells with dedifferentiated or stem-like properties; the ontogeny of these cells is unclear, but they are thought to carry a more malignant capacity than their differentiated counterparts. Cdx2 is a transcriptional factor that specifies cell fate of the intestinal epithelium. Epigenetic studies have demonstrated that Cdx2 loss alters chromatin structure in the intestinal epithelium. Cdx2 loss is often observed during colon tumor progression and is correlated with de-differentiation. Our current study is aimed to test the hypothesis that the Cdx2 prevents tumor progression by maintaining the tumor epigenome. To this end, we have generated two mouse models to determine the effect of Cdx2 loss on chromatin structure in a tumorigenic environment and in primary tumors. Our current studies are aimed at comparing Cdx2 binding sites on the genome in a normal and tumorigenic environment, and in defining how Cdx2 loss affects chromatin structure in primary tumors. These studies will shed light on how alterations in chromatin structure can contribute to the epigenomic mechanisms of colon tumor progression. Note: This abstract was not presented at the meeting. Citation Format: Ansu O. Perekatt, Ritu Rana, Namit Kumar, Michael Valdez, Michael Verzi. Role of Cdx2 in maintainining differentiated chromatin structure during tumor progression. [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 2089. doi:10.1158/1538-7445.AM2015-2089