tbuckley/cabot-search huggingface dataset:
Enhanced anti-tumor effects of the PD-1/PD-L1 blockade by combining a highly absorptive form of NF-kB/STAT3 inhibitor curcumin
Authors: Taeko Hayakawa, Juri Sugiyama, Tomonori Yaguchi, Atsushi Imaizumi, Yutaka Kawakami
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts The PD-1/PD-L1 blockade is now recognized as one of the basic immune interventions for development of combination cancer immunotherapy. We have been screening chemical libraries to obtain compounds which have an activity to augment anti-tumor activity of the PD-1/PD-L1 blockade.
<i>RUNX3</i> Methylation Reveals that Bladder Tumors Are Older in Patients with a History of Smoking
Authors: Erika M. Wolff, Gangning Liang, Connie C. Cortez, Yvonne C. Tsai, J. Esteban Castelao, Victoria K. Cortessis, Denice D. Tsao-Wei, Susan Groshen, Peter A. Jones
Journal: Cancer Research (2008)

Abstract Exposure to tobacco smoke is associated with increased DNA methylation at certain genes in both lung and bladder tumors. We sought to identify interactions in bladder cancer between DNA methylation and a history of smoking, along with any possible effect of aging. We measured DNA methylation in 342 transitional cell carcinoma tumors at BCL2, PTGS2 (COX2), DAPK, CDH1 (ECAD), EDNRB, RASSF1A, RUNX3, TERT, and TIMP3. The prevalence of methylation at RUNX3, a polycomb target gene, increased as a function of age at diagnosis (P = 0.031) and a history of smoking (P = 0.015). RUNX3 methylation also preceded methylation at the other eight genes (P &amp;lt; 0.001). It has been proposed that DNA methylation patterns constitute a “molecular clock” and can be used to determine the “age” of normal tissues (i.e., the number of times the cells have divided). Because RUNX3 methylation increases with age, is not present in normal urothelium, and occurs early in tumorigenesis, it can be used for the first time as a molecular clock to determine the age of a bladder tumor. Doing so reveals that tumors from smokers are “older” than tumors from nonsmokers (P = 0.009) due to tumors in smokers either initiating earlier or undergoing more rapid cell divisions. Because RUNX3 methylation is acquired early on in tumorigenesis, then its detection in biopsy or urine specimens could provide a marker to screen cigarette smokers long before any symptoms of bladder cancer are present. [Cancer Res 2008;68(15):6208–14]
Exenatide-Associated Ischemic Renal Failure
Authors: Wolfgang J. Weise, Mala S. Sivanandy, Clay A. Block, Richard J. Comi
Journal: Diabetes Care (2009)

Exenatide is a synthetic peptide that belongs to a new class of antidiabetes agents known as incretin mimetics. Like the endogenous incretin hormone glucagon-like peptide 1 (GLP-1), exenatide effectively lowers blood glucose levels by stimulating insulin release, inhibiting glucagon secretion, and delaying gastric emptying. Nausea and vomiting are the most common adverse reactions, which lead to discontinuation in as many as 14% of patients in one study (1).

We report on four patients (three male and one female; age 52–73 years) with exenatide-associated renal failure who presented with nausea, vomiting, or decreased fluid intake. All patients had type 2 diabetes with or without mild microalbuminuria and hypertension. They were taking …
Integrated molecular pathology accurately determines the malignant potential of pancreatic cysts
Authors: Mohammad Al-Haddad, Thomas Kowalski, Ali Siddiqui, Howard Mertz, Damien Mallat, Nadim Haddad, Nidhi Malhotra, Brett Sadowski, Mark Lybik, Sandeep Patel, Emuejevoke Okoh, Laura Rosenkranz, Michael Karasik, Michael Golioto, Jeffrey Linder, Marc Catalano
Journal: Endoscopy (2014)

<b>Background and study aims:</b> Current diagnostic testing is inadequate to determine the malignant potential of pancreatic cysts, resulting in overcautious patient management. Integrated molecular pathology (IMP) testing combines molecular analysis with first-line test results (cytology, imaging, and fluid chemistry) to assess the malignant potential of pancreatic cysts. This multicenter study aimed to determine the diagnostic accuracy of IMP for pancreatic adenocarcinoma, and the utility of IMP testing under current guideline recommendations for managing pancreatic cysts. <b>Patients and methods:</b> Patients who had undergone previous IMP testing as prescribed by their physician and for whom clinical outcomes were available from retrospective record review were included (n = 492). Performance was determined by correlation between clinical outcome and previous IMP diagnosis ("benign"/"statistically indolent" vs. "statistically higher risk [SHR]"/ "aggressive") or an International Consensus Guideline (Sendai 2012) criteria model for "surveillance" vs. "surgery." The Cox proportional hazards model determined hazard ratios for malignancy. <b>Results:</b> Benign and statistically indolent IMP diagnoses had a 97 % probability of benign follow-up for up to 7 years and 8 months from initial IMP testing. SHR and aggressive diagnoses had relative hazard ratios for malignancy of 30.8 and 76.3, respectively (both <i>P</i> < 0.0001). Sendai surveillance criteria had a 97 % probability of benign follow-up for up to 7 years and 8 months, but for surgical criteria the hazard ratio was only 9.0 (<i>P</i> < 0.0001). In patients who met Sendai surgical criteria, benign and statistically indolent IMP diagnoses had a > 93 % probability of benign follow-up, with relative hazard ratios for SHR and aggressive IMP diagnoses of 16.1 and 50.2, respectively (both <i>P</i> < 0.0001). <b>Conclusion:</b> IMP more accurately determined the malignant potential of pancreatic cysts than a Sendai 2012 guideline management criteria model. IMP may improve patient management by justifying more relaxed observation in patients meeting Sendai surveillance criteria. IMP can more accurately differentiate between the need for surveillance or surgery in patients meeting Sendai surgical criteria.
Positive Selection in the Carbohydrate Recognition Domains of Sea Urchin Sperm Receptor for Egg Jelly (suREJ) Proteins
Authors: Silvia A. Mah, Willie J. Swanson, Victor D. Vacquier
Journal: Molecular Biology and Evolution (2004)

A wealth of evidence shows that protein-carbohydrate recognition mediates the steps of gamete interaction during fertilization. Carbohydrate-recognition domains (CRDs) comprise a large family of ancient protein modules of approximately 120 amino acids, having the same protein fold, that bind terminal sugar residues on glycoproteins and polysaccharides. Sea urchin sperm express three suREJ (sea urchin receptor for egg jelly) proteins on their plasma membranes. suREJ1 has two CRDs, whereas suREJ2 and suREJ3 both have one CRD. suREJ1 binds the fucose sulfate polymer (FSP) of egg jelly to induce the sperm acrosome reaction. The structure of FSP is species specific. Therefore, the suREJ1 CRDs could encode molecular recognition between sperm and egg underlying the species-specific induction of the acrosome reaction. The functions of suREJ2 and suREJ3 have not been explored, but suREJ3 is exclusively localized on the plasma membrane over the sperm acrosomal vesicle and is physically associated with sea urchin polycystin-2, a known cation channel. An evolutionary analysis of these four CRDs was performed for six sea urchin species. Phylogenetic analysis shows that these CRDs were already differentiated in the common ancestor of these six sea urchins. The CRD phylogeny agrees with previous work on these species based on one nuclear gene and several mitochondrial genes. Maximum likelihood shows that positive selection acts on these four CRDs. Threading the suREJ CRDs onto the prototypic CRD crystal structure shows that many of the sites under positive selection are on extended loops, which are involved in saccharide binding. This is the first demonstration of positive selection in CRDs and is another example of positive selection acting on the evolution of gamete-recognition proteins.
VLA-4 integrin can mediate CD11/CD18-independent transendothelial migration of human monocytes.
Authors: H E Chuluyan, A C Issekutz
Journal: Journal of Clinical Investigation (1993)

The migration of human monocytes across unactivated and activated human umbilical vein endothelium (HUVE) in response to chemotactic factors was studied, and the adhesion molecules involved were characterized. Migration of blood monocytes or U937 cell line-derived monocytes across unactivated HUVE induced by C5a, was partially inhibited (by 75%) by mAbs (R15.7 or 60.3) to CD18 of the CD11/CD18 complex on the monocyte. However, when the HUVE was pretreated for 5 h with IL-1 alpha (0.1 ng/ml), TNF-alpha (100 U/ml), or LPS (1 ng/ml), migration induced by C5a was no longer inhibited; i.e., migration became CD18 independent. The monocyte CD18-independent migration was completely blocked by mAbs against alpha 4 or beta 1 integrin chains of VLA-4. This migration was also partially inhibited by mAbs against vascular cell adhesion molecule-1 (VCAM-1), a major counter-receptor on HUVE for VLA-4, but not by mAbs to E-selectin or intercellular adhesion molecule-1. The significant CD18-independent migration across "unactivated" HUVE was also inhibited by mAbs against alpha 4 or beta 1 chains of VLA-4, although mAbs against VCAM-1 did not inhibit under these conditions. Finally, considerable VLA-4-dependent transendothelial migration to C5a was also observed with monocytes from a patient with CD18 deficiency (leukocyte adhesion deficiency). These results suggest that (a) there is a major CD18-independent component in monocyte chemotactic factor-dependent migration across activated and unactivated endothelium; (b) that VLA-4 integrin on the monocyte has a major role in this migration; and (c) that VCAM-1 on activated endothelium functions as a counter-receptor in this process, but other ligands for VLA-4, especially on unactivated endothelium, may also be involved.
Abstract 584: Vitamin D suppresses pro-inflammatory cytokines and microRNAs in 3D prostatic co-cultures
Authors: Angeline Antonio Giangreco, Larisa Nonn
Journal: Cancer Research (2012)

Abstract MiRNAs are involved in the progression and regulation of inflammation and the immune response in cancer. Understanding the interplay between miRNAs and inflammation in the prostate may be beneficial for the treatment or prevention of prostate cancer (PCa) with anti-inflammatory agents such as vitamin D. We previously found that vitamin D effectively blocked inflammatory cytokine signaling and secretion in primary cultures of normal prostatic epithelial cells. Because inflammatory signaling relies on the crosstalk between epithelial, stromal, and immune cells, our new studies use a human prostate 3-dimensional co-culture model of primary human prostatic epithelial (PrE) cells and stromal (PrS) cells. Single PrE cells seeded in matrigel were grown into spheroid structures termed prostaspheres (PS). Simulating an inflammatory trigger from immune cells with TNF-α and IL-1α (T+I), we found a prolonged inflammatory response in our co-cultures that persisted beyond 24 hours as compared to the transient response in monolayer cultures. IL-6 expression increased and persisted beyond 24 hours after T+I exposure in both the PrS and PS-PrE cells. However, only in the PS-PrE cells did vitamin D blocked IL-6 expression. Cytokine array profiling revealed that vitamin D decreased expression of many T+I-induced cytokine genes, including TNF, IL-1A, IL-8, CCL7. CCL5, and CXCL10. MicroRNAs are also mediators of inflammation. A miRNA microarray demonstrated that miR-146a, -155, and -223, and other miRNAs were altered by cytokine stimulation in co-culture. MiR-146a is a known mediator of inflammation and vitamin D significantly reduced T+I-stimulated miR-146a expression in both PS-PrE and PrS cells. These data demonstrate that vitamin D is involved in the regulation of inflammation at both the mRNA and the miRNA level in a novel 3D prostasphere co-culture model. As miR-146a is found to be down-regulated in PCa, further studies will determine the role of T+I and/or vitamin D in co-cultures of PS-PrE (normal) and PS-PrECa (Cancer) on miR-146a to further understand vitamin D's inflammatory role in cancer. Our model provides a more in vivo-like method to study inflammation in PCa. We will fully validate these in vitro results in laser-capture-microdissected patient tissue from a vitamin D clinical trial, in which patients were supplemented with 400-40,000 IU/day of vitamin D3 prior to radical prostatectomy. Our results should shed light on the complex inflammatory signaling pathways in the prostate and provide further evidence for anti-inflammatory benefits of vitamin D supplementation. 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 584. doi:1538-7445.AM2012-584
TREATMENT OF UTERINE DISPLACEMENTS.
Authors: AUGUSTUS P. CLARKE
Journal: JAMA (1884)

Read before the Gynæcological Society of Boston, Nov. 13, 1884. Perhaps in no other department of gynæcological practice has a subject been more thoroughly considered than that of the treatment of uterine dispiacements, and although much has been achieved in this direction by the study, still there remains much diversity of opinion in regard to the propriety and method of such treatment. From the earliest times physicians have recognized the discomforts of uterine displacements, and have sought in some manner to rectify them, and for such relief a great variety of devices have been used. The ancients made use of medicated pessaries, which they distinguished into astringent, opiate, aperient, emollient, etc. The solid pessaries are composed of cork, ivory, wood, gum elastic, sponge, caoutchouc, silver, lead, zinc, copper, glass and other peculiar substances, and often coated or concealed by soft rubber or other protective, as the peculiar symptoms, or as
Computational Identification of a p38SAPK-Regulated Transcription Factor Network Required for Tumor Cell Quiescence
Authors: Alejandro P. Adam, Ajish George, Denis Schewe, Paloma Bragado, Bibiana V. Iglesias, Aparna C. Ranganathan, Antonis Kourtidis, Douglas S. Conklin, Julio A. Aguirre-Ghiso
Journal: Cancer Research (2009)

Abstract The stress-activated kinase p38 plays key roles in tumor suppression and induction of tumor cell dormancy. However, the mechanisms behind these functions remain poorly understood. Using computational tools, we identified a transcription factor (TF) network regulated by p38α/β and required for human squamous carcinoma cell quiescence in vivo. We found that p38 transcriptionally regulates a core network of 46 genes that includes 16 TFs. Activation of p38 induced the expression of the TFs p53 and BHLHB3, while inhibiting c-Jun and FoxM1 expression. Furthermore, induction of p53 by p38 was dependent on c-Jun down-regulation. Accordingly, RNAi down-regulation of BHLHB3 or p53 interrupted tumor cell quiescence, while down-regulation of c-Jun or FoxM1 or overexpression of BHLHB3 in malignant cells mimicked the onset of quiescence. Our results identify components of the regulatory mechanisms driving p38-induced cancer cell quiescence. These may regulate dormancy of residual disease that usually precedes the onset of metastasis in many cancers. [Cancer Res 2009;69(14):5664–72]
Effects of a short-term fast on albumin synthesis studied in vivo, in the perfused liver, and on amino acid incorporation by hepatic microsomes
Authors: Marcus A. Rothschild, Murray Oratz, Joseph Mongelli, Sidney S. Schreiber
Journal: Journal of Clinical Investigation (1968)

Carbonate-(14)C was used to label the hepatic intracellular arginine pool and direct measurement of albumin synthesis was made in six rabbits before and after an 18-36 hr fast. 18 perfusion studies were performed with livers derived from fed and fasted rabbits (18-24 hr). Microsomal amino acid-incorporating ability with leucine-(3)H and phenylalanine-(14)C was compared in 17 studies, using microsomes isolated from livers taken from fed and fasted rabbits and from isolated perfused livers whose donors were fed and fasted. Albumin synthesis is rapidly inhibited by fasting. Albumin synthesis decreased 33% in vivo and 53% in the perfused liver. The microsomes from perfused livers taken from fed animals did not demonstrate a significantly reduced capacity to incorporate leucine-(3)H or phenylalanine-(14)C into protein. Microsomes derived from perfused and nonperfused livers whose donors were fasted incorporated 32-54% less tracer than microsomes obtained from fed donor rabbits. Microsomes separated from perfused livers removed from fed and fasted rabbits responded to polyuridylic acid stimulation and phenylalanine-(14)C incorporation rose from 58 to 171%. An 18-36 hr fast inhibits albumin production in vivo and in the perfused liver. The microsomal system is less active in the fasted state and perfusion per se does not inhibit the microsomal response.
Nails: Therapy, Diagnosis, Surgery
Authors: William P. Coleman
Journal: JAMA (1990)

"What! Another book on nails?" So begins the preface to<i>Nails: Therapy, Diagnosis, Surgery</i>. Drs Scher and Daniel are well aware that many other textbooks and articles have been written in recent years on diseases and surgery of the nail. They have obviously evaluated the competition and attempted to outdo them all. They have succeeded masterfully. Advances in the biology of the nail have opened the doors for treating many conditions considered hopeless only a generation ago. As Scher and Daniel point out, people are concerned about their nails. "In 1988, $1.5 billion was spent on nail cosmetics in the United States alone." In an age of cosmetic improvement, we cannot overlook nails as an area of great concern to many individuals; thus, the importance of this fine textbook. The shorter of the book's two sections, on the normal nail, is a comprehensive review of its biology. Sections on structure
Role of Ga-67 Citrate Imaging in Extrapulmonary Pneumocystis in HIV Positive Patients
Authors: VANI VIJAYAKUMAR, CARLOS BEKERMAN, MICHAEL J. BLEND, STEVEN PINSKY
Journal: Clinical Nuclear Medicine (1993)

Gallium-67 citrate imaging is a highly sensitive examination for early detection of Pneumocystis carinil pneumonia in HIV infected patients. However, its role in the detection of extrapulmonary Pneumocystis remains to be defined. Common extrapulmonary localizations of Pneumocystis carinii in AIDS patients include lymph nodes, bone marrow, liver, and spleen. Thyroid, choroid, skin, ear, and Gl tract are less frequently involved. Extrapulmonary Pneumocystis carinii involvement of the thyroid causing hypothyroidism recently has been reported. Presented is an AIDS patient with a recent thyromegaly and laboratory diagnosis of hypothyroidism whose gallium scan demonstrates diffuse increased gallium uptake by the thyroid gland, which was proven to be secondary to Pneumocystis carinii.
Abstract LB-333: A case-parent-triad approach in assessing risk of osteosarcoma associated with genetic variation in insulin-like growth factor 1/growth hormone axis genes: a Children's Oncology Group (COG) study
Authors: Jessica Musselman, Tracy Bergemann, Mark Krailo, David Malkin, Julie Ross, Sharon Savage, Rajaram Nagarajan, Charles Sklar, Logan Spector
Journal: Cancer Research (2012)

Abstract Osteosarcoma (OS) is a rare malignant bone tumor with an overall incidence rate of 4.6 cases per million children aged 0-19 years in the United States. OS incidence peaks sharply in adolescence coinciding with the pubertal growth spurt. While the etiology of OS is largely unknown, its distinctive age-incidence pattern suggests that growth and development is crucial in the genesis of OS. Prior studies have suggested that variants in genes in the insulin-like growth factor 1 (IGF1)/growth hormone (GH) axis pathway are associated with OS. We assessed this hypothesis by examining 307 single nucleotide polymorphisms (SNPs) in 12 genes from this pathway (GHRH, GH1, GHR, GHRHR, IGF1, IGF1R, IGF2, IGF2R, IGFBP1, IGFBP3, IGFBP6, AND IGFALS) in a case-parent-triad study of cases and their biological parents. The sample included 229 complete triads and 56 dyads diagnosed during 2008-2011 at Children's Oncology Group institutions. Buccal cell samples were collected via the Oragene kit (DNA Genotek, Ottawa, Ontario) and returned by mail; genotyping was conducted by Sequenom iPLEX Gold method. We used log-linear models to estimate relative risks (RR) and 95% confidence intervals (CI) associated with transmitting one or two copies of the variant compared to no copies. After Bonferroni correction, 2 SNPs in IGFBP1 (rs10231774: RR = 1.44 and 0.07 for 1 and 2 vs. 0 copies, respectively; p &amp;lt; 0.001) and IGFALS (rs2575352: RR = 2.82 and 0.22 for 1 and 2 vs. 0 copies, respectively; p &amp;lt; 0.001), both in the upstream coding regions of IGF pathway genes, were significantly associated with OS incidence. These results confirm previous findings that variation in the IGF1/GH axis influence OS risk and further support the axis’ biologically and epidemiologically plausible role in OS development. 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-333. doi:1538-7445.AM2012-LB-333
Studies of Blood Enzymes In Mongolism
Authors: Beale H. Ong
Journal: JAMA (1966)

<h3>To the Editor:—</h3> In previous communications (<i>Lancet</i><b>1</b>:1191,1965;<i>New Eng J Med</i><b>273</b>:1356, 1965) we reported diminished levels of whole blood serotonin and significantly increased levels of leukocyte, erythrocyte, and whole blood galactose<sup>1</sup>-phosphate-uridylyltransferase, leukocyte acid and alkaline phosphatases, erythrocyte glucose-6-phosphate dehydrogenase and leukocyte-5-nucleotidase in patients with trisomic mongolism. Normal values were found in the translocation type of mongolism (Down's syndrome). Further studies of the same group of 12 trisomic and 12 translocation mongols matched by age and sex with 12 healthy controls are the subject of the present report. The selection of patients, materials, and chemical methods used have been previously described. Plasma hydroxyproline was measured by the method of LeRoy et al<sup>1</sup>and the following five plasma enzymes were assayed according to Sigma<sup>2</sup>: leucine aminopeptidase, fructose aldolase, isocitric dehydrogenase, glutamic pyruvic transaminase, and creatine phosphokinase. <h3>Results:—</h3> The results are summarized in the Table. Plasma leucine
Hemodynamic Findings Following Replacement of the Mitral Valve with the University of Cape Town Prosthesis
Authors: W. BECK, D. J. G. FERGUSSON, C. N. BARNARD, V. SCHRIRE
Journal: Circulation (1965)

Postoperative hemodynamic studies have been performed on 11 subjects following replacement of the mitral valve. In eight cases a comparison was made with the preoperative findings. The great improvement in the functional capacity of most patients is reflected in the findings of this study, which indicate a small gradient at rest across the prosthesis and no mitral incompetence. The residual gradient was thought to be due mainly to inadequate orificial size, although delay in reaching the fully open position may also play a part. In two subjects a severely elevated pulmonary vascular resistance fell markedly following the relief of left atrial hypertension. Two patients failed to show sustained clinical and hemodynamic improvement. In one, mild aortic valve disease was present and severe systemic hypertension developed, resulting in death. The influence of these factors is discussed. In the other, the cause for the continuing heart failure with poor left ventricular contractility was undetermined.