tbuckley/cabot-search huggingface dataset:
Abstract LB-195: Immune responses against cancer stem cell-specific tumor antigens and tumor microenvironment
Authors: Toshihiko Torigoe, Yoshihiko Hirohashi, Reina Morita, Satoshi Nishizawa, Kazuyo Yasuda, Akari Takahashi, Yasuaki Tamura, Noriyuki Sato
Journal: Cancer Research (2012)

Abstract Cancer stem cell (CSC) is a small population of cancer cells with stem cell-like phenotype and highly tumorigenic capacity. It is known that they are resistant to conventional chemotherapy and radiotherapy, therefore being responsible for cancer recurrence and metastasis. However, it has been unclear if immune responses against CSCs can overcome the therapeutic resistance of CSCs. In this paper, I would like to present unique immunopathological properties of CSCs, including (1) anti-stress genes expressed preferentially in CSCs, (2) immune responses against CSC-specific tumor antigens and (3) tumor microenvironment modulated by CSCs. We could isolate CSCs from a variety of solid cancer cell lines such as breast, lung, colon, kidney, ovarium and endometrium cancer lines by using Hoechst33342 staining assay and ALDH1 activity assay. Comparative gene expression analysis using DNA microarray revealed a number of stress responsive genes that are preferentially expressed in CSCs such as genes encoding heat shock proteins (HSPs), stress-activated protein kinases, ABC transporters, oxidoreductases, and detoxification enzymes. Interestingly, some of them are expressed exclusively in testis among normal adult tissues. DNAJB8 was one of the CSC-preferential HSPs. RNAi-mediated knockdown of DNAJB8 could reduce the tumor forming capacity of CSCs, while its overexpression enhanced the tumorigenic capacity. Our findings account for the molecular basis of stress-resistant property of CSCs and highlight a novel strategy and molecular targets for CSC-specific cancer therapy. We next examined if immune responses against CSCs could be induced by immunization with CSC-specific gene products such as SOX2, DNAJB8 and OR7C1. CSC-specific cytotoxic T-cell clones were established from peripheral blood lymphocytes of cancer patients and we confirmed that CSCs were susceptible to T-cell-mediated cytotoxicity in vitro. Our data indicated that CSC antigens might serve as potent tumor vaccines for CSC-targeted immunotherapy. However, some CSCs had the property of immunoescape through modulation of tumor microenvironment. CSCs could recruit stromal cells that produced immunosuppressive cytokines. The role of stromal cells that interact with CSCs would be discussed. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-195. doi:1538-7445.AM2012-LB-195
¿ES NECESARIO SUSPENDER EL TRATAMIENTO ANTIAGREGANTE ANTES DE REALIZAR UNA PUNCION GUIADA POR ECOENDOSCOPIA (USE-PAAF)?
Authors: E Vázquez-Sequeiros, F González Panizo, J Ramón Foruny, V Defarges, C González García, J Ángel González Martín, D Juzgado, D Boixeda de Miquel
Journal: Endoscopy (2012)

Introducción: Las guías de práctica clínica existentes en la actualidad aconsejan, siempre que sea posible, suspender los fármacos antiagregantes plaquetarios antes de realizar maniobras terapéuticas. La información existente sobre este tema para la USE-PAAF es reducida. Objetivo: Analizar de forma prospectiva la tasa de complicaciones y el perfil de seguridad de la USE-PAAF en pacientes (Pac.) que reciben tratamiento con fármacos antiagregantes. Método: Periodo inclusión: 01/10–04/12. Criterios inclusión: 1.) Pac. que reciben tratamiento antiagregante (aas/clopidogrel) y que por su elevado riesgo trombótico/isquémico se desaconseja suspenderlo para USE-PAAF. 2.) USE-PAAF es necesaria para diagnosticar/tratar al Pac. Criterios de exclusión: 1.) Pac. con coagulopatía. 2.) Pac. rechaza USE-PAAF. Se evaluaron dos cohortes de Pac.: 1.) COHORTE 1: Pac. antigregados que no suspendieron el tratamiento antiagregante pre-PAAF; 2.) COHORTE 2 (Grupo control): Pac. antiagregados que suspendieron el tratamiento antiagregante pre-PAAF en el mismo periodo de tiempo. Todos los Pac. incluidos presentaban lesiones peri-intestinales sólidas (adenopatía/tumor páncreas) suspectibles de USE-PAAF, siendo biopsiados con ecoendoscopio lineal y aguja de punción de 22 G y citopatólogo en la sala. Se evaluaron las posibles complicaciones (hemorrágicas o no) durante la USE-PAAF y a los 7días (contacto telefónico) Resultados: En el periodo de tiempo descrito se han incluido 25 Pac. antiagregados (AAS: 4/25=16%; clopidogrel: 21/25=84%) (COHORTE 1) y 50 controles (pacientes no antiagregados: COHORTE 2). Pac. de COHORTE 1 Eran mayores (79 a vs. 64a; p 0.05). La precisión global alcanzada por USE-PAAF en la COHORTE 1 y 2 era del 92% (23/25) y 90% (45/50), respectivamente (p>0.05). No se registraron complicaciones de tipo hemorrágico clínicamente significativas en ninguna de las lesiones biopsiadas en ambas cohortes (0% vs. 0%; p>0.05). La tasa de complicaciones de la COHORTE 1 (4%) y 2 (2%) no diferían significativamente (p>0.05). En la COHORTE 1 un Pac. (en tratamiento con AAS) presentó datos ecoendoscópicos compatibles con sangrado interno en la adenopatía (engrosamiento hipoecogénico post-PAAF) sin repercusión clínica En la COHORTE 2: un Pac. presentó pancreatitis leve, sin descenso del Hcto. Conclusiones: 1.) Los resultados de este estudio sugieren que puede realizarse USE-PAAF con seguridad en aquellos pacientes con lesiones sólidas a los que no se les puede suspender la medicación antiagregante (AAS o clopidogrel).
Reactivation of Genital Herpes Simplex Virus Type 2 Infection in Asymptomatic Seropositive Persons
Authors: Anna Wald, Judith Zeh, Stacy Selke, Terri Warren, Alexander J. Ryncarz, Rhoda Ashley, John N. Krieger, Lawrence Corey
Journal: New England Journal of Medicine (2000)

Most persons who have serologic evidence of infection with herpes simplex virus (HSV) type 2 (HSV-2) are asymptomatic. Historically, it has been assumed that these persons have less frequent viral reactivation than those with symptomatic infection.
Improving periodontal outcomes: merging clinical and behavioral science
Authors: Rebecca S. Wilder, Kimberly S. Bray
Journal: Periodontology 2000 (2016)

Abstract New data indicate that periodontal diseases are much more prevalent than previously thought, which means that there are large numbers of patients who will need to be diagnosed and treated for periodontal disease in a general dental practice. Oral hygiene procedures performed by patients between office visits are important for gingival health. No particular type of toothbrush has consistently been shown to have superior plaque‐removal ability over another. Although studies on powered brushes have shown evidence for efficacy of biofilm removal and increased patient compliance, they are of short duration, making evaluation of long‐term effects difficult to achieve. Interdental cleaning with dental floss can be effective but it is technique‐sensitive. Interdental brushes have been shown to be superior to floss in plaque index scores, but not in gingival inflammation reduction. A systematic review of oral irrigation reported a beneficial adjunctive effect on bleeding and gingival indices and pocket depth. Antimicrobials in mouthrinses and toothpastes have shown significant reductions in plaque and gingivitis when used correctly. Even though it is considered essential for patients to utilize biofilm‐removal techniques on a frequent basis, studies on adherence show that approximately 30–60% of health information is forgotten within 1 h, and 50% of health recommendations are not followed. Incorporating psychosocial aspects of behavioral change, including well‐established counseling strategies, such as motivational interviewing, may elicit improved patient outcomes.
COMPARISON OF THE EFFECTIVENESS OF DIFFERENT STRATEGIES FOR EMPLOYING NONINVASIVE STRESS TO ASSESS CARDIAC PROGNOSIS.
Authors: Alan Rozanski, Howard Staniloff, Jamshid Maddahi, John Friedman, Nicholina Said, Alan Waxman, Daniel Berman
Journal: Clinical Nuclear Medicine (1986)

Rozanski, Alan; Staniloff, Howard; Maddahi, Jamshid; Friedman, John; Said, Nicholina; Waxman, Alan; Berman, Daniel Author Information
Abstract 1599: Expression of therapeutics targets in osteosarcoma : Effects of chemotherapy and evolution of disease
Authors: Yvonne M.H. Versleijen-Jonkers, Addy C.M. van de Luijtgaarden, Manon A. Leus, Melissa H.S. Roeffen, Uta E. Flucke, Ingrid C.M. van der Geest, Winette T.A. van der Graaf
Journal: Cancer Research (2010)

Abstract Introduction The receptor activator of nuclear factor kb/-ligand/osteoprotegerin (RANK/RANKL/OPG) triad and insulin-like growth factor 1 receptor (IGF1R) system are potential therapeutic targets in osteosarcoma. We studied the consistency of expression of specific targets over time and across lesions within subjects. This aids to select biomarkers for future therapies and to determine an optimal sequence of targeted and cytotoxic therapy. Materials and methods Immunohistochemical staining was performed on paraffin-embedded therapy-naïve biopsies, post-neoadjuvant chemotherapy resection specimens, and metastatic lesions for RANK, OPG, IGF1R, IGF1, phosphorylated protein kinase B (pAKT), mammalian target of rapamycin (pMTOR) and extracellular-regulated kinase (pERK). Staining intensity was scored as absent (0), weak (1) or strong (2). Change of expression between lesions within subjects was interrogated by Wilcoxon signed rank tests. Results 49 tumor samples of 28 patients were available (staining results presented in table 1). No change in RANK or OPG expression was observed. After chemotherapy pERK (p=0.008) and pMTOR expression (p=0.015) decreased; pERK and IGF1R expression (both p=0.046) were lower in metastases than in primary tumors. Expression of IGF1 and pAKT remained unchanged. Discussion The choice for a therapeutic regimen is increasingly guided by presence of specific molecular alterations in tumor tissue. Variation of target expression over time and across lesions within subjects is a known phenomenon in common cancers. In osteosarcomas, we found a rather consistent expression signature with the exception of pERK, pMTOR and IGF1R, which were downregulated after exposure to chemotherapy or in metastatic lesions. Conclusion Screening for biomarkers for specific targeted drugs in osteosarcoma should not be limited to a single tumor sample. It is likely from our data that an optimal sequence of targeted therapies and cytotoxic drugs exists.Table 1:Staining results (%) Biopsy (n=28)Resection (n=13)Metastasis (n=8)Intensity012012012RANK014860158513088OPG4544383954255025IGF140960217900100IGF1R778681577145729pmTOR252946691515431443pAKT11503931393129710pERK001005404650050 Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 1599.
Pregnancy, Parturition, and Prostaglandins: Defining Uterine Leiomyomas
Authors: Kimberley Cesen-Cummings, John A Copland, J. Carl Barrett, Cheryl L Walker, Barbara J Davis
Journal: Environmental Health Perspectives (2000)

Leiomyomas, benign smooth muscle tumors of the uterus, are the most common gynecologic neoplasm in women. Studies with surgically resected human tissues and primary cultures have revealed that several genes are differentially expressed in leiomyomas compared to matched normal myometrium. An estrogen-driven pattern of gene expression in leiomyomas, similar to that seen in normal myometrium during pregnancy and parturition, is associated with a persistent inappropriate response of neoplastic myometrial smooth muscle cells to ovarian hormones. This is possibly due to aberrant expression levels or signaling via estrogen and progesterone receptors. We propose the hypothesis that uterine leiomyomas mimic a differentiated myometrial cell at pregnancy and exhibit a hypersensitivity to sex steroid hormones that prevents the cells from responding to normal apoptotic or dedifferentiation signals and from returning to a nongravid phenotype. Support of this hypothesis is derived from experimental studies in female Eker rats that develop uterine leiomyomas with many similarities to the human disease. Our hypothesis accounts for the benign nature of these tumors and their high incidence in women during the reproductive years. By identifying the factors that participate in parturition and involution of the pregnant myometrium, we may better define uterine leiomyomas and thus identify novel targets for therapeutic strategies to treat these tumors.
Abstract 3451: Cell proliferation and apoptosis during chloroform-induced hepatocarcinogenesis in male F-344/N rats
Authors: Julia H. Carter, Harry W. Carter, Raymond E. Richmond, James A. Deddens, Nancy Chiu, Anthony B. DeAngelo
Journal: Cancer Research (2010)

Abstract The carcinogenic potential of chlorinated organics is of direct importance in human risk assessment. Most drinking water chlorinated organics are disinfection by products (DBPs) of water chlorination and many test positive in rodent bioassays. Trihalomethanes (THMs) are the most prevalent DBPs generated in chlorinated drinking water and chloroform (TCM) is the THM in highest concentration in finished drinking water. Human exposure to TCM occurs through ingestion of drinking water, inhalation and dermal exposure. TCM is carcinogenic to the liver and kidney of rodents including male and female B6C3F1 mice and male F-344/N and Osborne-Mendel rats. The carcinogenic mechanism of TCM in the rodent is not completely understood. Four mechanisms have been proposed: 1) mutagenicity; 2) reparative hyperplasia; 3) altered gene expression; and 4) secondary genotoxicity. Here, histopathology, immunohistochemistry, and quantitative image analysis were used to examine reparative cell proliferation and altered gene expression as potential mechanisms of TCM-induced hepatocellular carcinogenesis in male F-344/N rats. Animals were exposed to concentrations of 803 + 5 or 1592 + 21 mg/L in the drinking water for 78 or 100 weeks. Distilled water was the vehicle control. The high TCM dose increased the prevalence (% of animals with a lesion) of hepatocellular neoplasia (carcinoma and adenoma) 17.5% vs. 5.1% (p&amp;lt;0.05) and marginally enhanced the prevalence of combined preneoplastic and neoplastic tumors (20.5% vs 7.7%; 0.05&amp;lt;p&amp;lt;0.1). Cell proliferation (proliferating cell nuclear antigen), apoptosis (terminal transferase assay) and expression of tumor associated markers, transforming growth factor alpha (TGF-α) and the p21 Ras oncogene were evaluated in normal liver, altered foci (AF), large foci of cellular alteration (LFCA) and adenomas (AD). PCNA, TGF-α, and p21 Ras increased significantly during TCM-induced neoplastic progression (p = 0.0021, 0.0105, and 0.0167, respectively). A significant change in apoptosis was not found during neoplastic progression, however, a progressive imbalance between cell proliferation and death occurred (p = 0.0022). The phenotype of hepatocellular lesions in rats receiving TCM in their drinking water differed from that of the “spontaneous” lesions arising in rats given distilled water, suggesting a different mechanistic origin. Taken together the data are consistent with a carcinogenic mechanism for TCM that includes adaptation to a hepatotoxic chemical and selection of resistant cells. (This abstract does not reflect the views of the EPA). 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 3451.
Abstract 1222: Down-regulation of MEIS2 leads to apoptosis in human colorectal cancer cells
Authors: Chang Soo Hong, Xue-Feng Zhao, Sung Min Moon, Hye Won Lee, Snag Rok Lee, Yong Kyu Park
Journal: Cancer Research (2010)

Abstract Three amino-acid loop extension (TALE) homeobox proteins MEIS2 is a transcriptional factor that regulates the expression of large sets of downstream target genes by direct binding to their promoter DNA. MEIS2 controls cell growth and differentiation during embryogenesis and carcinogenesis and is overexpressed in ovarian and pancreas cancer. However, the underlying cellular mechanisms remain largely unsolved. In this study, we report that MEIS2 is aberrantly expressed in colorectal adenocarcinoma cells and is profound proliferative and anti-apoptotic effects against colon cancer cells. In immunohistochemical staining, MEIS2 is positively stained in colorectal adenocarcinoma cells and has strong intensity in its nucleus, compared to normal colonic crypt cells. We found that down-regulation of MEIS2 by specific shRNA inhibited the cell growth (50% decrease as compared with control cultures, P&amp;lt;0.001) of HCT-116 colon cancer cell, due to an increase apoptosis (from 3% in control cultures to 65% after 72 hour from transient transfection of MEIS2 shRNA, P&amp;lt;0.001) as determined by MTT and FACScan apoptosis assay. Knockdown of MEIS2 by specific shRNA transfection reduced the expression of Akt, and decreased the phosphorylation of its downstream target proteins such as forkhead transcription factors (FoxO) and p27, and increased the nuclear localization of nonphosphorylated FoxO and p27, which result in activation of apoptosis. In summary, our data indicate that MEIS2 promotes cell growth and plays critical role as novel anti-apoptotic factor through regulation of Akt expression within Akt/PKB signaling pathway in colorectal cancer. 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 1222.
Abstract LB-25: Global phosphoproteomics reveals crosstalk between Bcr-Abl and negative feedback mechanisms controlling Src signaling
Authors: Liudmilla Rubbi, Björn Titz, Lauren Brown, Erica Glavan, Evangelia Komisopoulou, Sharon S. Chen, Tracey Low, Martik Tahmasian, Brian Skaggs, Markus Müschen, Matteo Pellegrini, Thomas G. Graeber
Journal: Cancer Research (2011)

Abstract In subtypes and late stages of leukemias driven by the tyrosine kinase fusion protein Bcr-Abl, signaling by the Src family kinases (SFKs) critically contributes to the leukemic phenotype. We performed global tyrosine phosphoprofiling using quantitative mass spectrometry of Bcr-Abl transformed cells in which the activities of the Src family kinases were perturbed to build a detailed context-dependent network of cancer signaling. Perturbation of the SFKs Lyn and Hck with genetics or inhibitors revealed Bcr-Abl downstream phosphorylation events either mediated by or independent of SFKs. We identified multiple negative feedback mechanisms within the network of signaling events affected by Bcr-Abl and SFKs, and found that Bcr-Abl attenuated these inhibitory mechanisms. The Csk binding protein Pag1 (also known as Cbp) and the tyrosine phosphatase Ptpn18 both mediated negative feedback to SFKs. We observed Bcr-Abl-mediated phosphorylation of the phosphatase Shp2 (Ptpn11) and this may contribute to the suppression of these negative feedback mechanisms to promote Bcr-Abl-activated SFK signaling. Csk and a kinase-deficient Csk mutant both produced similar globally repressive signaling consequences, suggesting a critical role for the adaptor protein function of Csk in its inhibition of Bcr-Abl and SFK signaling. The identified Bcr-Abl-activated SFK regulatory mechanisms are candidates for dysregulation during leukemia progression and acquisition of SFK-mediated drug resistance. 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-25. doi:10.1158/1538-7445.AM2011-LB-25
Abstract 5455: Antitumor activity of death receptor agonists for prostate cancer therapy
Authors: Sharmila Shankar, Luke Marsh, Chris Jackman, Rakesh K. Srivastava
Journal: Cancer Research (2010)

Abstract Clinical trials on TRAIL and death receptor (TRAIL-R1 and TRAIL-R2) agonist antibodies are being carried out through out the world. Until today, there are no small organic molecules that bind to TRAIL-death receptors, and induce apoptosis mainly in cancer cells. Through molecular and biological approaches, we have identified novel death receptor agonists (small molecular weight organic compounds). Death receptor agonists termed as “DRAs” inhibited cell viability and colony formation, and induced apoptosis in androgen-dependent (LNCaP) and -independent (PC-3) human prostate cancer cell lines, but had no effect on human normal prostate epithelial cells and hepatocytes. The combinations of DRAs with TRAIL had additive effects on apoptosis in prostate cancer cells. Commonly used anticancer drugs further enhanced the apoptosis-inducing potential of DRAs. DRAs recruited FADD and activated caspase-8, and thus formed active TRAIL-DISC (death-inducing signaling complex) similar to that of TRAIL. DRAs inhibited the growth of PC-3 and LNCaP xenografts in nude mice, and prostate cancer growth in TRAMP mice. In vivo, DRAs inhibited tumor cells proliferation (Ki67 staining) and induced caspase-3 activity and apoptosis (TUNEL staining). Pharmacokinetics data demonstrate that DRA is stable, possesses a long terminal half-life, and meats the criteria of clinical trials. Our data suggest, for the first time, that DRAs are specific activators of death receptor pathway of apoptosis, and can be used to treat human prostate cancer. Further studies are underway to assess their clinical significance for the treatment of prostate cancer. (Funding Support: Department of Defense, US Army) 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 5455.
How feasible is sub-specialisation for diagnostic EUS?
Authors: L Doig
Journal: Endoscopy (2006)

Background: Training opportunities to meet the wide demands EUS are few, hindering the expansion of services. Conventional approaches have not resolved this problem. The natural division between diagnostic and therapeutic EUS raises the question of whether sub-specialisation is feasible and whether there might be a role for the non-physician endoscopist (NE).
Abnormalities of B-Cell Activation and Immunoregulation in Patients with the Acquired Immunodeficiency Syndrome
Authors: H. Clifford Lane, Henry Masur, Lynn C. Edgar, Gail Whalen, Alain H. Rook, Anthony S. Fauci
Journal: New England Journal of Medicine (1983)

We studied B-lymphocyte function in 12 homosexual male patients with the acquired immunodeficiency syndrome, 5 healthy homosexual men, and 12 heterosexual controls. In comparison with the heterosexual controls, the patients were found to have elevated numbers of cells spontaneously secreting immunoglobulin, decreased B-cell proliferative responses to T-cell-independent B-cell mitogens, and qualitatively deficient helper T cells. The hyperactive spontaneous B-cell responses as well as the refractoriness to signals for T-cell-independent B-cell activation were highly suggestive of an in vivo polyclonal activation of B cells and may have been responsible for the manifestations of B-cell hyperreactivity, such as hypergammaglobulinemia, seen in these patients. We conclude that the scope of immune dysfunction in the acquired immunodeficiency syndrome involves B cells as well as T cells.