tbuckley/cabot-search huggingface dataset:
Abstract 5326: MicroRNA profiles discriminate among colon cancer metastasis.
Authors: Mario Acunzo, Jerry G. Nuovo, Nicola Zanesi, Giampiero Di Leva, Flavia Pichiorri, Stefano Volinia, Cecilia Fernandez, Stefan Costinenan, Arianna Bottoni, Aaron Burch, Hansjuerg Alder, Laura Conti, Anna Antenucci, Immacolata A. Rosito, Antonio Ciardi, Chang G. Liu, Alessandra Drusco, Carlo M. Croce
Journal: Cancer Research (2013)

Abstract MicroRNAs are being exploited for diagnosis, prognosis and monitoring of cancer and other diseases. Their small non immunogenic size, high tissue specificity, and critical role in oncogenesis provide new biomarkers for diagnosing and classifying cancer as well as predicting patients’ outcomes. MicroRNAs signatures have been identified for many human tumors, including colorectal cancer. This tumor affects about one million individuals in developed countries, and about half of them die for recurrences. In most cases, metastatic disease is difficult to predict and to prevent with adequate therapies. The identification of microRNAs signatures for metastatic disease, could aid to define the risk and localization of recurrences in patients with unknown micrometastasis. In this study, tissues of three different groups of colorectal cancer (CRC) patients were analyzed: microarray and cards analysis were performed on 66 patients with or without lymph nodes and/or liver recurrences; a second group of 16 metastatic patients were selected for RT-PCR; finally, in situ hybridization was carried out on tissue cores arrays belonging to a different set of patients with and without positive lymph nodes and/or liver metastasis. MicroRNA-31, 21, 93, and 103 up-regulation together with miR-566 down-regulation defined the CRC metastatic signature. Moreover, in situ hybridization data defined metastatic localization: miR-200c up-regulation together with miR-566 down-regulation characterized lynphonodal invasion, while liver recurrences were defined by miR-31, 93 and 103 over-expression. Citation Format: Mario Acunzo, Jerry G. Nuovo, Nicola Zanesi, Giampiero Di Leva, Flavia Pichiorri, Stefano Volinia, Cecilia Fernandez, Stefan Costinenan, Arianna Bottoni, Aaron Burch, Hansjuerg Alder, Laura Conti, Anna Antenucci, Immacolata A. Rosito, Antonio Ciardi, Chang G. Liu, Alessandra Drusco, Carlo M. Croce. MicroRNA profiles discriminate among colon cancer metastasis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5326. doi:10.1158/1538-7445.AM2013-5326
CHOLESTERYL ESTER TRANSFER PROTEIN LEVELS AND CALCIUM SCORE AS RISK PREDICTORS OF CARDIOVASCULAR OUTCOMES
Authors: George Marzouka, Abdulla Damluji, Alexis Rodriguez, Lynda Otalvaro Orozco, Raul Mitrani, Carlos Alfonso, Mauricio Cohen, Mauro Moscucci, Robert Hendel
Journal: Journal of the American College of Cardiology (2014)
Five to Eight-Year Follow-up of Patients Undergoing Porcine Heart-Valve Replacement
Authors: Lawrence H. Cohn, Gilbert H. Mudge, Frederick Pratter, John J. Collins
Journal: New England Journal of Medicine (1981)

To evaluate the clinical course after porcine heart-valve replacement, we followed 128 patients for five to eight years after surgery. Aortic-valve replacement was performed in 47 patients, mitral-valve replacement in 62, and combined aortic-valve and mitral-valve replacement in 19. Four patients died within 30 days of surgery (operative mortality, 3 per cent), and 20 died later (16 per cent); the actuarial probability of survival at eight years for all patients was 80 +/- 4 per cent (mean +/- S.E.M.). Thromboemboli were found in two of 43 patients after aortic-valve replacement, in nine of 62 after mitral-valve replacement, and in four of 18 after combined aortic-valve and mitral-valve replacement. Valve dysfunction resulted from bacterial endocarditis in five patients (4 per cent) and from primary valve dysfunction in another five.
Updated results of BICC-C study comparing first-line irinotecan/fluoropymidine combinations with or without celecoxib in mCRC: Updated efficacy data
Authors: C. Fuchs, J. Marshall, E. Mitchell, R. Wierzbicki, V. Ganju, M. Jeffery, J. Schultz, D. A. Richards, R. Soufi-Mahjoubi, J. Barrueco
Journal: Journal of Clinical Oncology (2007)

4027 Background: This multicenter, randomized study assessed efficacy &amp; safety for irinotecan/fluoropyrimidines combinations in previously untreated mCRC. Methods: Pts were randomized to: infusional FOLFIRI, modified bolus IFL (mIFL), or CapeIri; and concurrent celecoxib or placebo in a double-blind fashion. The protocol was amended in April 2004: bevacizumab (bev) was added to the FOLFIRI and mIFL arms, whereas CapeIri was discontinued. Period 1 (P1) and Period 2 (P2) designate subjects enrolled before or after the amendment. Initial efficacy &amp; safety analyses were reported at ASCO ’06. We now report follow-up of 46 months for P1 and 31 months for P2. Results: 430 pts were treated in P1 and 117 pts in P2. Baseline characteristics and post-study treatment were balanced. P1 results: Median progression free survival (PFS) was 7.6 mos for FOLFIRI; 5.9 mos for mIFL (p=0.004); and 5.8 mos for CapeIri (p=0.015). Median overall survival (OS) was 23.1 mos for FOLFIRI; 17.6 mos for mIFL (p=0.087); and 18.9 mos for CapeIri (p=0.27). One-year survival rate favored FOLFIRI (75%) compared to either mIFL (65%) or CapeIri (66%). Overall Response Rate (ORR) was 47% in FOLFIRI, 43% in mIFL, 39% in CapeIri (not significantly different). P2 results: Median PFS was 11.2 mos for FOLFIRI+bev and 8.3 mos for mIFL+bev (p=0.28). Median OS was not reached for FOLFIRI+bev but was 19.2 mos for mIFL+bev (p=0.007). One-year survival rate favored FOLFIRI+bev (87%) when compared to mIFL+bev (61%). ORR was 58% for FOLFIRI+bev and 54% for mIFL+bev (p=0.73). Common grade = 3 AEs are listed below. Celecoxib did not impact safety or efficacy. Conclusions: First line FOLFIRI or FOLFIRI+bev were superior to their comparators and show favorable results in survival and tolerability in untreated mCRC. Median survival for FOLFIRI+bev has not been reached. [Table: see text] No significant financial relationships to disclose.
Abstract 3676: A selective small molecule inhibitor of c-Jun N-terminal kinase 1
Authors: Ke Yao, Yong-Yeon Cho, Ann M. Bode, Anuradha Vammenthala, Jewn Giew Park, Kangdong Liu
Journal: Cancer Research (2010)

Abstract The c-Jun N-terminal kinases (JNKs) are members of the mitogen-activated protein (MAP) kinase family. The jnk1 and jnk2 genes are expressed ubiquitously, whereas jnk3 has a limited pattern of expression and is largely restricted to brain, heart, and testis. The JNKs signal transduction pathway was shown to play an important role in coordinating various cellular responses including apoptosis, proliferation, and neoplastic transformation. Indiscriminately suppressing the activity of all three c-Jun N-terminal kinase isoforms, JNK1, JNK2, and JNK3, is probably not an appropriate strategy because each JNK appears to have a distinct function in cancer, asthma, diabetes, and Parkinson's disease. However, until now, isoform selective inhibitors for JNK1 over JNK2 or JNK3 activities have not been developed. Therefore, using structure-based design, we developed (in-house) a selective isoform inhibitor that showed a selective inhibitory effect against JNK1, but not JNK2 or JNK3. We found that 7-(6-N-Phenylaminohexyl)amino-2H-anthra[1,9-cd]pyrazol-6-one (AV-7) suppressed JNK1 activity, with no effect on either JNK2 or JNK3, in vitro. In cell culture systems, we also found that AV-7 inhibited JNK1 activity dose-dependently. In contrast to SP600125, a non-selective JNKs inhibitor, that binds to the ATP active site, AV-7 was designed to target the protein-protein interaction between JNK1 and its binding partner(s) rather than the ATP binding site. At 10 μM, AV-7 specifically inhibited JNK1 by about 50%. The phosphorylation of c-Jun by JNKs induces c-Jun transactivation and transcriptional activity through the formation of a protein complex with c-Fos or ATF1 (i.e., AP-1 complex). c-Jun/AP-1 enhances transcription by binding to the promoter region of many genes. We found that AV-7 inhibits UVB-induced c-Jun phosphorylation and sub-G1 accumulation in JNK2−/− MEFs, which express only JNK1, but had no effect on c-Jun in JNK1−/− MEFs, which only express JNK2. These results demonstrate that AV-7 is an isoform selective JNK1 inhibitor. In humans, JNKs play a key role in obesity-induced type 2 diabetes mellitus and the absence of JNK1 results in decreased adiposity, significantly improved insulin sensitivity and an enhanced insulin receptor signaling capacity in mouse obesity models. Therefore, we suggest that because of JNK1's critical role in diabetes, AV-7 might have therapeutic potential against this devastating disease. 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 3676.
Abstract 2902: Phosphorylation of 12 lipoxygenase at Tyrosines 19 and 614 regulates its activity during beta4 integrin signaling
Authors: Ashok Kumar Dilly, Keqin Tang Tang, Yande Guo Guo, Sangeeta Joshi, Prasanna Ekambaram, Krishna Rao Maddipati, Yinlong Cai, Stephanie Tucker, Kenneth Honn
Journal: Cancer Research (2011)

Abstract 12-Lipoxygenase (12-LOX) converts arachidonic acid to 12(S)-hydroxyeicosatetraenoic acid 12(S)-HETE, an eicosanoid implicated in tumor angiogenesis, growth, and metastasis. We have demonstrated previously that 12-LOX interacts with integrin beta4 cytoplasmic domain by using yeast two hybrid system. Integrins are involved in metastasis by mediating attachment and migration of cells, as well as through transducing signals. Increased expression of 12-LOX and beta4 integrin have been documented in a number of carcinomas. The purpose of this study is to find out the mechanisms underlying the signaling pathways in 12-LOX mediated cancer progression. The phosphorylation of beta4 integrin, Src, and 12-LOX were analyzed using specific antibodies against phospho-tyrosine, phospho-beta4 integrin, Phospho-Src (pSrc). c-Src activity and association was determined in beta4 integrin immunoprecipitate. The HEK293 cells transiently transfected with wild type or dominant negative (DN) Src were used as in vitro models to study the regulation of 12-LOX activity. The 12-LOX product 12(S)-HETE was analyzed by using an analytical liquid chromatography-tandem mass spectrometry.12-LOX tyrosine phosphorylation sites mutants viz., 19, 295, and 614 were used to study the effect on its activity upon beta4 ligation. We show here that the cytoplasmic domain of beta4 integrin, can interact specifically with pSrc after beta4 integrin ligation in A431 cells. Herein we report that beta4 integrin ligation resulted in significant increase in 12(S)-HETE level in A431 cells, compared to that of unligated beta4 integrin. An increase in Src kinase activity was found in beta4 integrin ligation of A431 cells and inhibition of Src kinase by PP2 or DN Src significantly reduced 12(S)-HETE production. The ligation of beta4 integrin induces src activation, which resulted in tyrosine phosphorylation of 12-LOX. The residues that are important for 12-LOX activity and tyrosine phosphorylation were mapped to Y19 and Y614. We examined that 12-LOX mutants (Y19F and Y614F), showed 70% less enzymatic activity, compared to wild type 12-LOX. Furthermore, we showed that the 12-LOX activity modulated by these residues impacts migration in HUVEC cells. To our knowledge, this is the first report to show that Src kinase activity is required for beta4 integrin mediated regulation of 12-LOX, which may in turn regulate metastatic potential of cancer cells. 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 2902. doi:10.1158/1538-7445.AM2011-2902
SP0097 How can i Still be Me?
Authors: S. Collins
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> The onset of chronic illness is a threat, not only to one’s body but also to emotional wellbeing. I will explain how various stages of adaptation over 33 years of living with rheumatoid arthritis have been facilitated and impeded by internal and external influences. Adaptation has involved facing fear, anger and loss. It has also meant the renegotiation of relationships, both intimate and professional but above all, with myself. I will suggest that positive adaptation requires: a reconstruction of one’s internal world and the reclaiming of personal power; that the ability to adapt and self- manage is not a permanent state - it can be affected by disease activity and one’s environment; and I suggest that a challenge for health professionals will be to motivate patients without insinuating that the absence of an innate ability to adapt is a ‘failing’. <h3>Disclosure of Interest</h3> None Declared
Increased Clotting Factors in Pregnancy
Authors: Liberto Pechet, Benjamin Alexander
Journal: New England Journal of Medicine (1961)

MORE than seventy years ago Virchow1 postulated three etiologic factors in thrombotic disease: blood hypercoagulability, blood stasis and vascular injury. There is now no question that the last two of the triad are extremely important, but there is still considerable controversy regarding increased blood clottability as a significant pathogenetic factor. A positive answer would raise hope for a specific test for diagnosis and management of the thrombotic state. Recent notable advances in the knowledge of coagulation prompted us to re-examine this question.The pregnant state was selected as the initial area of study because it constitutes a common, temporary, reversible . . .
CLINICAL OUTCOMES OF A SECOND-GENERATION, SELF-EXPANDING TAVR SYSTEM: A SINGLE-CENTER EXPERIENCE
Authors: Dimytri A. Siqueira, Alexandre Abizaid, Auristela Ramos, Andréia Jeronimo, David Le Bihan, Rodrigo B. Barreto, Antonio Kambara, Magaly Santos, Ibraim Pinto, Laura Brenton, Helge Moellmann, Amanda Sousa, J. Eduardo Sousa
Journal: Journal of the American College of Cardiology (2016)
ET-32 * HYPOXIA REDUCTION IN INTRACRANIAL GLIOBLASTOMA MODELS BY OMX-4.80P, A PEGylated ENGINEERED H-NOX OXYGEN CARRIER THAT IS LONG-LASTING IN CIRCULATION AND SAFE
Authors: N. Le Moan, J. Getz, S. Ng, T. Davis, C. Bedard, A. Davis, P. Leung, L. Serwer, K. Tanaka, T. Keating, F. Yan, J. Winger, S. Cary, A. Krtolica
Journal: Neuro-Oncology (2014)

BACKGROUND: Hypoxic cells in solid tumors are resistant to radiotherapy. Omniox has developed a novel class of oxygen carrier proteins termed H-NOX, engineered to deliver oxygen selectively into hypoxic tissues. Previous studies have shown that one of our H-NOX candidates, OMX-4.80, penetrates intracranial glioblastoma (GB) tumors in mice, and in a dose dependent manner decreases tumor hypoxia and extends survival when combined with radiotherapy. However, we discovered that the circulation half-life of OMX-4.80 is ∼1h in dogs, which may limit clinical utility. To improve the circulation half-life, we developed a PEGylated version of OMX-4.80 (OMX-4.80P). The aim of this study was to characterize the pharmacokinetic and safety profile of OMX-4.80P and examine its effect on tumor hypoxia. METHODS: After intravenous administration of OMX-4.80P to mice and rats bearing GB tumors, we collected tumors, blood and plasma, and analyzed OMX-4.80P pharmacokinetics, immunogenicity and its effects on blood cell counts and chemistries. We evaluated OMX-4.80P bio-distribution by immunohistochemistry and its effect on tumor hypoxia by ELISA of endogenous (HIF-1a) and exogenous (pimonidazole) hypoxia markers. RESULTS: Compared to OMX-4.80, OMX-4.80P has an increased stability and circulation half-life (30h vs. 1h), significantly longer tumor accumulation (48h vs. 4h), and is not immunogenic. Furthermore, OMX-4.80P crosses the blood tumor barrier in several different intracranial rodent GB models and reduces HIF-1a and pimonidazole accumulation by ∼50%. Pharmacokinetic and toxicology studies in rodents and dogs showed that OMX-4.80P is well tolerated, and has a circulation half-life of ∼52h in dogs. The resulting exposure is expected to be sufficient for OMX-4.80P to accumulate in human GB tumors and reduce hypoxia. CONCLUSIONS: In summary, the increased retention of OMX-4.80P in circulation, the longer exposure achieved in solid tumors and efficiency in delivering oxygen into hypoxic tissues suggest OMX-4.80P is a promising IND candidate for radiation therapy enhancement in GB.
“Feeding the Baby”-Serum and Other Supplements to Chemically Defined Medium1
Authors: William G. Taylor
Journal: JNCI Journal of the National Cancer Institute (1974)

Journal Article “Feeding the Baby”-Serum and Other Supplements to Chemically Defined Medium Get access William G. Taylor William G. Taylor 2Tissue Culture Section, Laboratory of Biology, National Cancer Institute, National Institutes of Health, Public Health Service, U.S. Department of Health, Education, and Welfare, Bethesda, Md. 20014. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 53, Issue 5, November 1974, Pages 1449–1457, https://doi.org/10.1093/jnci/53.5.1449 Published: 01 November 1974
Metastatic Prostate Cancer With Restored Hormone-Response After Radioligand Therapy With 177Lu-PSMA-617
Authors: Carl Diedrich Schlenkhoff, Eberhard Knüpfer, Markus Essler, Hojjat Ahmadzadehfar
Journal: Clinical Nuclear Medicine (2016)

An 80-year-old patient with castrate-resistant prostate cancer presented to our department for PSMA imaging because of a rising prostate-specific antigen (PSA) level. The tumor was diagnosed in 2004. GnRh analog was the only treatment the patient received. Two cycles of 177Lu-PSMA-617 were performed with a 2-month interval in between. Ten months after finishing with 2 cycles of Lu-PSMA therapy, we noticed a continuous falling PSA level and a decreasing tumor spread in the PET/CT imaging just under the hormone therapy.
THU0106 Lysophosphatidic Acid Receptor LPA1 is Essential for Development of Arthritis
Authors: Y. Miyabe, C. Miyabe, Y. Iwai, A. Takayasu, S. Fukuda, W. Yokoyama, J. Nagai, M. Jona, Y. Tokuhara, R. Ohkawa, H. M. Albers, H. Ovaa, J. Aoki, J. Chun, Y. Yatomi, H. Ueda, M. Miyasaka, N. Miyasaka, T. Nanki
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Lysophosphatidic acid (LPA) is a bioactive lipid that binds to a group of cell surface G protein-coupled receptors (LPA<sub>1-6</sub>) and has been implicated as an important mediator of angiogenesis, inflammation and cancer growth [1-3]. <h3>Objectives</h3> To explore the pathogenic roles of LPA<sub>1</sub> on rheumatoid arthritis, we examined the effects of LPA<sub>1</sub> on immune function and development of arthritis. <h3>Methods</h3> Expression of LPA receptors on the synovial tissue was analyzed by immunohistochemistry and quantitative RT-PCR. Effect of abrogation of LPA<sub>1</sub> on collagen-induced arthritis (CIA) was evaluated using LPA<sub>1</sub>-deficient mice or LPA<sub>1</sub> antagonist. Fluorescence labeled-CD11b<sup>+</sup> splenocytes were transferred into CIA mice. Twenty-four hours after the transfer, the numbers of labeled cells in the synovium were counted under fluorescent microscopy. CD4<sup>+</sup> naïve T cells were incubated with T helper (Th)1-, Th2-, or Th17-polarizing conditions and Th differentiation was analyzed. Osteoclast formation from bone marrow cells was examined. <h3>Results</h3> LPA<sub>1</sub> was highly expressed in the synovium of rheumatoid arthritis (RA) compared to osteoarthritis. LPA<sub>1</sub>-deficient mice failed to develop arthritis following collagen type-II (CII) immunization. LPA<sub>1</sub> antagonist ameliorated murine CIA. Abrogation of LPA<sub>1</sub> was associated with reduced cell infiltrates, bone destruction in the joints, and IL-17 production from CII-stimulated splenocytes. Infiltration of transferred LPA<sub>1</sub>-deficient CD11b<sup>+</sup> macrophages into the synovium was suppressed compared with wild-type macrophages. LPA<sub>1</sub> antagonist inhibited the infiltration of wild-type macrophages. Differentiation into Th17, but not Th1 or Th2, and osteoclast formation were also suppressed in LPA<sub>1</sub>-deficienct mice or LPA<sub>1</sub> inhibition <i>in vitro</i>. <h3>Conclusions</h3> LPA-LPA<sub>1</sub> signaling critically contributes to the development of arthritis by cellular infiltration, Th17 differentiation and osteoclastogenesis, suggesting that LPA<sub>1</sub> is a promising target molecule for RA therapy. <h3>References</h3> Schleicher SM, et al. PLoS One. 2011; 6: e22182. Xu X, et al. Cancer. 2010; 116: 1739-1750. Houben AJ, et al. Cancer Metastasis Rev. 2011; 30: 557-565. <h3>Disclosure of Interest</h3> None Declared
Taxol Researchers Continue Forging Ahead
Authors: K. Nagy
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article Taxol Researchers Continue Forging Ahead Get access Kate Nagy Kate Nagy Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 1, 5 January 1994, Pages 8–10, https://doi.org/10.1093/jnci/86.1.8 Published: 05 January 1994
Multiple-Antibiotic-Resistant Pathogenic Bacteria -- A Report on the Rockefeller University Workshop
Authors: Alexander Tomasz
Journal: New England Journal of Medicine (1994)

Last year, a small group of scientists, physicians, and public health experts gathered at Rockefeller University for a one-day workshop to discuss the accelerating spread of bacterial pathogens resistant to antimicrobial agents and whether multiresistant bacteria pose a threat to public health in the United States. This report is based on the conclusions of that workshop. After a half-century of virtually complete control over microbial disease in the developed countries, the 1990s have brought a worldwide resurgence of bacterial and viral diseases1. An important factor in this phenomenon is the acquisition of antibiotic-resistance genes by virtually all major bacterial . . .
Bacterial Pneumonia in Persons Infected with the Human Immunodeficiency Virus
Authors: Robert E. Hirschtick, Jeffrey Glassroth, Matthew C. Jordan, Timothy C. Wilcosky, Jeanne M. Wallace, Paul A. Kvale, Norman Markowitz, Mark J. Rosen, Bonita T. Mangura, Philip C. Hopewell
Journal: New England Journal of Medicine (1995)

Patients with human immunodeficiency virus (HIV) infection are at increased risk for bacterial pneumonia in addition to opportunistic infection. However, the risk factors for bacterial pneumonia and its incidence in this population are not well defined.