tbuckley/cabot-search huggingface dataset:
Abstract P5-03-05: Histone deacetylase (HDAC)-inhibitor mediated reprogramming drives cancer cells to the pentose phosphate metabolic pathway
Authors: BG Debeb, RA Larson, L Lacerda, W Xu, DL Smith, NT Ueno, JM Reuben, M Gilcrease, S Krishnamurthy, TA Buchholz, WA Woodward
Journal: Cancer Research (2012)

Abstract Recent studies have shown that energy metabolism in human pluripotent cells contrasts sharply with energy metabolism in differentiated cell types. Specifically, it has been shown that nuclear reprogramming from somatic cells to induced pluripotent stem cells is associated with a switch from oxidative to glycolytic metabolism. Whether a metabolic switch also occurs in reprogrammed/dedifferentiated breast cancer cells is unknown. Moreover, the function of the metabolic state in stemness is poorly understood and no data are available on whether breast cancer stem cells (CSCs) are metabolically different from committed cancer cells. Herein we demonstrated that HDAC inhibitors reprogram committed single aldefluor negative breast cancer cells into aldefluor positive cells (10.3 ± 2.8 vs 21.3 ±3.7% untreated vs treated P &amp;lt;0.05, representing an average of 5 single cell derived clones) and promoted tumor initiation from non-initiating committed cells (p = 0.004). Further, induced stem-like cells were resistant to taxol and salinomycin, a drug previously described to target CSCs. These reprogrammed cancer cells have enhanced activity of the pentose phosphate pathway (PPP) with upregulation of G6PD expression and activity and higher levels of NADPH and ROS. Hypothesizing that CSCs may favor the PPP in order to survive and self renew, we used G6PD inhibitors, 6-AN and Imatinib, to target mammosphere formation and aldefluor activity in HDAC inhibition induced stem-like cells. Not only was there a significant decrease in mammospheres from reprogrammed cells, the aldefluor activity was totally blocked at a concentration that does not affect proliferation. This work demonstrates that HDAC inhibition mediated cancer cell dedifferentiation promotes metabolic reprogramming and highlights an FDA approved drug that targets metabolism in stem cell plasticity. Further functional endpoint studies are underway to validate these findings. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-03-05.
Abstract LB-251: The checkpoint molecules LAG-3 and PD-1 synergize to maintain tolerance to tumors
Authors: Monica V. Goldberg, Seng-Ryong Woo, Jaishree Bankoti, Mark Selby, Christopher J. Nirschl, Matthew L. Bettini, Peter Vogel, Joseph F. Grosso, George Netto, Alcides Chaux, Matthew Smeltzer, Creg J. Workman, Drew M. Pardoll, Alan J. Korman, Dario AA Vignali, Charles G. Drake
Journal: Cancer Research (2011)

Abstract Checkpoint molecules like CTLA-4 are important regulators of tumor-specific tolerance, and monoclonal antibodies that block this class of molecules have emerged as important therapeutic modalities in multiple cancer types. Recent data suggest that tumor infiltrating, non-functional ("exhausted") CD8 cells may express more than one checkpoint molecule, implying a more subtle control system for modulating CD8 T cell function in vivo. Based on their frequent co-expression on tumor-infiltrating lymphocytes, we investigated the relative roles of PD-1 (programmed death - 1) and LAG-3 (lymphocyte activation gene -3) in tumor tolerance. Single knockout (KO) mice lacking either of these genes were relatively unaffected, with PD-1 KO mice developing a late-onset strain-specific myocarditis. However, double knockout mice (DKO) lacking both PD-1 and LAG-3 developed early autoimmune pathology, with infiltrating lymphocytes present in multiple organs, and eventual lethality. More significantly, DKO mice spontaneously rejected the poorly immunogenic B16 melanoma, while rejection was not observed when either PD-1 or LAG-3 was knocked out individually. Moreover, established tumors in wild-type mice could be cured by combined treatment anti-PD-1 and anti-LAG-3 antibodies, while single antibody treatment was sufficient only to delay tumor outgrowth. Taken together, these data demonstrate a previously unappreciated synergy between these two checkpoint molecules in tumor-specific tolerance, and suggest a novel combinatorial strategy for cancer immunotherapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-251. doi:10.1158/1538-7445.AM2011-LB-251
Abstract 2745: Expression of immunoglobulin gene in myeloblasts from patients with acute myelogenous leukemia and its distinct VKJK recombination pattern
Authors: Xiaoyan Qiu, Xiaoping Sun, Zhiqiao He, Pei Lin, M. James You, Lei Chen, Chongwen Dai, C. Cameron Yin
Journal: Cancer Research (2010)

Abstract Immunoglobulin (Ig) gene expression is normally restricted to B lymphocytes and plasma cells. Immunoglobulin gene rearrangement has been used in the diagnosis and monitoring of response to therapy in B-cell lymphoma and leukemia. However, during the last decade, our group and others have found that Ig is also expressed in many non-hematopoietic cells, especially epithelial cancer cells. Moreover, we have reported that non-hematopoietic cancer-derived Ig expression is associated with poor prognosis, though the mechanism of its function in the survival of cancer cells is not yet known. In this study, we assessed the expression of Ig heavy chain (gamma and mu) and light chain (kappa) in myeloblasts (CD33+CD19-CD138-, sorted by FACs) from 16 patients with acute myelogenous leukemia (AML) and 6 AML cell lines by RT-PCR, ELISA, and immunohistochemistry. As control groups, we also evaluated IgG, IgM and IgK transcripts in monocytes and neutrophils (sorted by FACs) from 15 patients with non-hematopoietic malignancies and 8 healthy individuals. We have found that Ig gamma chain was expressed in 6 of 14 AML patients, but in none of the 23 controls. All of the variable region sequences of AML-derived Ig gamma chain showed diversity, similar to B cells-derived Ig gamma chain. In contrast, Ig mu chain was expressed in 7 of 14 AML cases, 3 of 15 monocytes and 1 of 10 neutrophils from non-hematopoietic cancers, and 4 of 8 monocytes and 2 of 8 neutrophils from healthy controls. All of the variable region sequences of AML-derived mu chain from any individual showed monoclonal pattern, but different individuals showed different sequences. Kappa light chain was expressed in 15 of 16 AML cases, 11 of 15 monocytes and 3 of 10 neutrophils from patients with non-hematopoietic cancers, and 1 of 8 monocytes and 1 of 8 neutrophils from healthy controls. Interestingly, the AML-derived Ig kappa transcripts showed unique VKJK rearrangement pattern with several predominant VKJK usages. In particular, the VK1-5/JK1-3 recombination was observed in 93/155 of VKJK sequences from 15 AML cases. The frequent expression of Ig in AML cells and the preferential usage of certain VKJK rearrangements by AML-derived Ig kappa light chain suggest a role of Ig in AML pathogenesis and a potential target for AML therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2745.
Abstract 1667: In vitro and in vivo validation of CSE1L/hCAS as a potential molecular target in pancreatic cancer
Authors: Kazim Husain, Domenico Coppola, Barbara Centeno, Richard Helm, Chen Dung-Tsa, Said Sebti, Mokenge Malafa
Journal: Cancer Research (2011)

Abstract Background: The human cellular apoptosis susceptibility protein (hCAS) is a Ran- binding protein playing a role as mitotic spindle checkpoint regulator and as nuclear export factor. hCAS expression is frequently altered in metastatic cancers. To date the role of hCAS in pancreatic cancer is unknown. Therefore this study aimed to investigate the role of hCAS in human pancreatic cancer in vitro and in vivo. Methods: The hCAS protein expression was determined using Western immunoblotting in human pancreatic cancer cell lines (AsPc-1, BxPc-3, Capan-2, MiaPaCa-2, Panc-1, and SW1990) and immortalized normal human pancreatic ductal epithelial cell (HPNE) and HPNE-Kras. siRNA induced hCAS knockdown pancreatic cancer cells were compared to scrambled siRNA cells with regard to proliferative (MTT assay), cell death, cell cycle (Trypan blue and Flow cytometry), malignant transformation (colony formation assay) and protein expression (Western and confocal microscopy). hCAS KD MiaPaCa-2 cells were xenografted in SCID nude mice. Tumor growth, expression of hCAS, proliferation index (Ki-67), and caspase-3 were immunostained in tumor tissues and compared with scr siRNA MiaPaCa-2 cells. Expression of hCAS was determined in human pancreatic tumor tissues using immunohistochemical stain. Results: hCAS protein expression was low in HPNE cells compared to HPNE-Kras. Lowest expression of hCAS noted in BxPc-3 cells compared to other pancreatic cancer cells. When compared to Scr-MiaPaCa-2, KD-MiaPaCa-2 cells demonstrated lower proliferation, G2/M phase cell cycle arrest, increased apoptosis, as well as inhibition of malignant transformation. Pancreatic ductal carcinomas (PCA) were hCAS strongly positive. Normal pancreatic ducts (ND) were hCAS weakly positive. hCAS KD-MiaPaCa-2 tumor growth was retarded in mice compared to Scr-MiaPaCa-2 tumors. hCAS KD-MiaPaCa-2 tumors showed hCAS depletion, lower proliferative index, increased caspase-3 immunostaining and PARP1 cleavage. Conclusion: This is the first report of hCAS expression in human pancreatic cancer. Our data suggest that hCAS is a regulator of cell proliferation, cell cycle regulation and apoptosis. hCAS may represent a potential chemopreventive and therapeutic target for human pancreatic cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1667. doi:10.1158/1538-7445.AM2011-1667
Interim Analyses in Clinical Trials: Why Do We Plan Them?
Authors: Sophie D. Fosså, Eva Skovlund
Journal: Journal of Clinical Oncology (2000)

Article Tools EDITORIAL Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2000.18.24.4007 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11118460 Interim Analyses in Clinical Trials: Why Do We Plan Them? Sophie D. FossåxSophie D. FossåSearch for articles by this author , Eva SkovlundxEva SkovlundSearch for articles by this author Show More Department of Medical Oncology and Radiotherapy The Norwegian Radium Hospital Oslo, Norway https://doi.org/10.1200/JCO.2000.18.24.4007 Full Text PDF Figures and Tables "Interim Analyses in Clinical Trials: Why Do We Plan Them? ." Journal of Clinical Oncology, 18(24), pp. 4007–4008© 2000 by American Society of Clinical Oncology
Abstract 1341: Early detection of tumor cells by innate immune cells leads to Treg recruitment through CCL22 production by tumor cells
Authors: Julien Faget, Cathy Biota, Thomas Bachelot, Michael Gobert, Colette Dezutter-Dambuyant, Isabelle Treilleux, Sophie Goddard-Leon, Jean Yves Blay, Christophe Caux, Christine Menetrier-Caux
Journal: Cancer Research (2010)

We recently obtained evidences, in breast carcinoma, that regulatory T cells (Treg) localized within lymphoid aggregates, but not in the tumor bed, have a negative impact on patients’ survival. Immunohistochemical analysis on paraffin embedded sections of tumors demonstrated correlation between CCL22 production tumor cells and Treg infiltration thus identifying CCL22 as a key mediator of intratumoral Treg recruitment (Gobert M., Cancer Res vol 69, p2000-9, 2009). Herein we decipher the mechanisms regulating CCL22 production by tumor cells.In vitro, human breast epithelial tumor cell lines secreted low CCL22 levels that were strongly increased in response to inflammatory signals (TNFα, IFNγ and IL-1β or their combination). Using an in vitro model we demonstrated that breast tumor cell lines (MCF-7, MDA-MB453, CLB-SAV, BT-474) but not immortalized normal breast epithelial cell line (Telma) secreted functional CCL22 in response to culture with PBMC or their supernatants. Addition of IL-1RA and anti-TNFα abrogated the CCL22 secretion demonstrating the importance of Il-1β and TNFα in CCL22 production. Depletion experiments demonstrated a major role of monocytes within PBMC in i) the induction of CCL22 and ii) the production of IL-1β and TNFα. However, co-culture of tumor cells with purified monocytes was not sufficient to reproduce the PBMC effects. The addition of rhIFNγ to tumor cell and monocyte co-cultures restored the CCL22 production by tumor cells and that of IL-1β by monocytes suggesting a role of IFNγ producing cells (T cells or NK cells) within PBMC.Taken together, these results demonstrate a dialogue between monocytes, tumor cells and IFNγ producers (NK or T cells) leading, through monocyte-derived IL-1β and TNFα, to CCL22 production by tumor cells and Treg recruitment. These observations would suggest that early tumor cell detection by innate effectors (monocytes, NK) would trigger CCL22 production by tumor cells and not normal mammary epithelial cells leading to Treg recruitment as a mechanism to stop the anti-tumor immune reactivity.Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1341.
Medullary Thyroid Carcinoma Imaged by Tc-99m MIBI SPECT and Tl-201 Chloride/Tc-99m Pertechnetate Subtraction SPECT
Authors: WEI-JEN SHIH, VICKIE STIPP, SYLVIA MAGOUN, KENNETH B. AIN, CALIXTO PULMANO
Journal: Clinical Nuclear Medicine (1996)

A 61-year-old man with medullary thyroid carcinoma and local invasion of the left lobe of the thyroid had Tc-99m MIBI SPECT and Tl-201 chloride/Tc-99m pertechnetate subtraction SPECT after left lobectomy of the thyroid, using a triple-headed gamma camera. Tl-201 chloride/Tc-99m pertechnetate subtraction demonstrated a large mass with high Tl-201 uptake in the left neck. Although there was intense uptake in the tumor in the left thyroid bed on Tc-99m MIBI neck SPECT, there was also uptake in both salivary glands and the right lobe of the thyroid gland. Thus, uptake in the right lobe of the thyroid gland and the salivary glands might not be differentiated from tumor invasion or metastasis from medullary cell carcinoma. Compared with MIBI SPECT, Tl-201 chloride/Tc-99m pertechnetate subtraction SPECT shows more apparent delineation of tumor uptake and may be a preferable technique.
Tc-99m Sestamibi Esophageal Activity During Myocardial Imaging
Authors: ELAZAR A. BIENENSTOCK, CHRIS RUSH
Journal: Clinical Nuclear Medicine (1998)

A 75-year-old woman with atypical chest pain was referred for a two-day protocol stress/rest dipyridamole Tc-99m sestamibi myocardial perfusion study. Myocardial perfusion was normal, but, unexpectedly, extensive linear activity in a distribution corresponding to the esophagus was detected on both studies. A diagnosis of noncardiac chest pain due to duodenogastro-esophageal bile reflux was made in view of normal myocardial perfusion and the recurrent copious esophageal activity on the two separate examination days. This case stresses the importance of actively searching for ancillary findings when performing functional nuclear medicine imaging.
Reply to Matsushita et al.
Authors: F. Tekin, O. Ozutemiz, G. Ersoz, O. Tekesin
Journal: Endoscopy (2009)

We thank Drs. Matsushita et al. for their letter and interest in our article [1]. Duodenal duplication cyst (DDC) is a benign congenital anomaly acquired during embryonic development of the digestive system [2]. Surgical resection is the standard therapy [3] [4]; however, the difficulty of the operative procedure owing to the close proximity of the major papilla has resulted in an interest in endoscopic therapies. Using the endoscopic needle-knife and sphincterotome to open the cyst into the duodenum [5] and endoscopic partial resection of the cyst [6] [7] are the favored endoscopic methods.
Whole-exome sequencing to identify genetic risk variants underlying inhibitor development in severe hemophilia A patients
Authors: Marcin M. Gorski, Kevin Blighe, Luca A. Lotta, Emanuela Pappalardo, Isabella Garagiola, Ilaria Mancini, Maria Elisa Mancuso, Maria Rosaria Fasulo, Elena Santagostino, Flora Peyvandi
Journal: Blood (2016)
PTH-012 Response To Peri-ampullary Botox Injection And Subsequent Long Term Response To Endoscopic Sphincterotomy In Type 2/3 Sphincter Of Oddi Dysfunction
Authors: K Wheeler, CA Salmon, AS Austin
Journal: Gut (2014)

<h3>Introduction</h3> Pain relief following the peri-ampullary injection of Botulinum toxin A may offer a safe alternative to biliary manometry that accurately identifies patients with Type 2/3 Sphincter of Oddi Dysfunction (SOD) who will benefit from endoscopic sphincterotomy. <h3>Methods</h3> From 2007 to 2012, patients with probable biliary or pancreatic type 2 or 3 Sphincter of Oddi Dysfunction based on Rome III revised Milwaukee criteria underwent injection of 100 units Botox divided into four quadrants close to the major papilla. Response was characterised as complete (CR), partial (at least 50% improvement) (PR) or no response (NR) using a 10-point Likert Scale. Patients that showed either CR or PR were offered an endoscopic sphincterotomy when symptoms returned or worsened. <h3>Results</h3> 91patients with median age 39 (22–64), 92.3% female were studied. 93% patients with suspected Type 2 biliary SOD (n = 15) had prior cholecystectomy: 73% had a response to Botox (5CR, 6PR). 7 underwent ES for recurrent symptoms, 2CR and 5PR (100% responders). The time from Botox to ES ranged from 12 to 42 weeks (median 20 weeks). Of the 7 who underwent ES 4 of the responders had no further intervention, 3 underwent extension of their ES for recurrent symptoms within 5 to 8 months. Of 3 NR to Botox who underwent ES only 1 responded. Of the NR none had any further intervention. 84% patients with suspected Type 3 biliary SOD (n = 64) had prior cholecystectomy: 53% had a response to Botox (17CR, 23PR). 26 underwent ES for recurrent symptoms, 8CR and 15PR (88% responders). Of 13 Botox NR who underwent ES, only 3 responded (23%). The time range from Botox to ES ranged from 6 to 58 weeks (median of 17.5 weeks). Of the 26 who underwent ES and were CR or PR 18 had no further intervention and 8 had extended ES for recurrent symptoms within 2 to 30 months. Of the 3 responders to ES but not Botox 2 had further ES 1 with CR and 1 NR. 83% patients with suspected Type 3 pancreatic SOD (n = 6) had prior cholecystectomy: 83% had a response to Botox (4CR, 1PR). 2 underwent ES within 12 to 19 weeks post Botox, and both responded with one having extension of ES for recurrent symptoms with a PR. <h3>Conclusion</h3> Botox injection identifies patients likely to respond to ES avoiding the risks of manometry. Manometry may be helpful in a proportion of Botox non-responder in whom SOD is still suspected. <h3>Disclosure of Interest</h3> None Declared.
Abstract 3129: Regulation of expression and role of the pigment epithelium derived factor in Ras-mediated pancreatic oncogenesis
Authors: Joanna Maya, Tyler Robin, Susan Crawford, Paul M. Campbell, Channing J. Der, Paul Grippo, Gretchen A. Repasky
Journal: Cancer Research (2010)

Abstract Mutated and constitutively activated Ras oncoproteins are found in ∼33% of all human cancers. In particular, Ras mutations are found in a majority of pancreatic cancers (90%), and aberrant Ras activation has been shown to be critical for promoting pancreatic adenocarcinomas. Ras-mediated transformation is associated with downregulation of Pigment Epithelium Derived Factor (PEDF), an anti-angiogenic and lipid regulatory factor shown to suppress oncogenic K-Ras-induced invasive disease in vivo. PEDF has also been shown to have anti-tumorigenic activity on tumor cells themselves. Specifically, mice with chronically active mutant KRAS(12D) background form precancerous lesions with high frequency, and knockout of PEDF expression specifically in pancreatic tissue resulted in a significant aggravation of the precancerous phenotype. The mechanism(s) of this biological phenotype is unclear and the specific role of PEDF as a potential tumor suppressor gene in Ras-mediated oncogenesis remains unresolved. Western analyses were used in this study to investigate the expression of PEDF in K-Ras-transformed and nontransformed human pancreatic duct-derived cells (HPNE) and their surrounding cell culture growth media. We observe that PEDF is upregulated both intracellularly under growth and serum-starved conditions and extracellularly under serum-starved conditions in K-Ras-transformed human pancreatic cells. We are also investigating the role of exogenous PEDF in cell proliferation induced by oncogenic variants of K-Ras. While no significant difference was observed in cell proliferation between the PEDF-treated and nontreated cells (whether they be K-Ras-transformed and nontransformed cells) in growth conditions, a decrease in cell proliferation was observed in the PEDF-treated K-Ras-transformed cells under serum-starved conditions. By better understanding the link between Ras and PEDF we will be able to assess the contribution and therapeutic potential of PEDF to formation and progression of pancreatic cancer while investigating novel targets for therapeutic intervention. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3129.
THE CLINICAL IMPACT OF TRANSRADIAL PERCUTANEOUS CORONARY INTERVENTION ON ACCESS SITE BLEEDING IN STEMI PATIENTS REQUIRING INTRA-AORTIC BALLOON PUMPING SUPPORT
Authors: Kazunori Horie, Yusuke Toki, Takashi Matsumoto, Norio Tada, Taku Honda, Kaname Takizawa, Tatsushi Otomo, Naoto Inoue
Journal: Journal of the American College of Cardiology (2016)
Case 27-2007
Authors: Ronald S. Gibbs, Drucilla J. Roberts
Journal: New England Journal of Medicine (2007)

A primigravida delivered a stillborn infant at 39.7 weeks' gestation. Testing was positive for group B streptococcus; she was immune to rubella, and the blood type was B Rh-positive. The pregnancy had been uneventful except for costochondritis 14 weeks before delivery and an oval-shaped red rash with central clearing on the thigh 6 weeks before delivery. On the day of admission, fetal movements ceased and contractions began. An external fetal monitor and ultrasonographic examination confirmed intrauterine fetal death.