tbuckley/cabot-search huggingface dataset:
Intratumor Heterogeneity Affects Gene Expression Profile Test Prognostic Risk Stratification in Early Breast Cancer
Authors: Rekha Gyanchandani, Yan Lin, Hui-Min Lin, Kristine Cooper, Daniel P. Normolle, Adam Brufsky, Michael Fastuca, Whitney Crosson, Steffi Oesterreich, Nancy E. Davidson, Rohit Bhargava, David J. Dabbs, Adrian V. Lee
Journal: Clinical Cancer Research (2016)

Abstract Purpose: To examine the effect of intratumor heterogeneity (ITH) on detection of genes within gene expression panels (GEPs) and the subsequent ability to predict prognostic risk. Experimental Design: Multiplexed barcoded RNA analysis was used to measure the expression of 141 genes from five GEPs (Oncotype Dx, MammaPrint, PAM50, EndoPredict, and Breast Cancer Index) in breast cancer tissue sections and tumor-rich cores from 71 estrogen receptor (ER)-positive node-negative tumors, on which clinical Oncotype Dx testing was previously performed. If the tumor had foci of high Ki67 (n = 26), low/negative progesterone receptor (PR; n = 13), or both (n = 5), additional cores were obtained. In total, 181 samples were processed. Oncotype Dx recurrence scores were calculated from NanoString nCounter gene expression data. Results: Hierarchical clustering using all GEP genes showed that majority (61 of 71) of tumor samples clustered by patient, indicating greater interpatient heterogeneity (IPH) than ITH. We found a strikingly high correlation between Oncotype Dx recurrence scores obtained from whole sections versus tumor-rich cores (r = 0.94). However, high Ki67 and low PR cores had slightly higher but not statistically significant recurrence scores. For 18 of 71 (25%) patients, scores were divergent between sections and cores and crossed the boundaries for low, intermediate, and high risk. Conclusions: Our study indicates that in patients with highly heterogeneous tumors, GEP recurrence scores from a single core could under- or overestimate prognostic risk. Hence, it may be a useful strategy to assess multiple samples (both representative and atypical cores) to fully account for the ITH-driven variation in risk prediction. Clin Cancer Res; 22(21); 5362–9. ©2016 AACR.
Abstract B18: A simple method to prepare oligonucleotide-conjugated antibodies for multiplex protein detection
Authors: Haibiao Gong, Ilona Holcomb, Aik Ooi, Xiaohui Wang, Daniel Majonis, Marc Unger, Ramesh Ramakrishnan
Journal: Cancer Research (2016)

Abstract With rapid advances in nucleic acid detection technologies, genomics studies are being conducted in highly multiplexed formats. However, multiplex analysis is still a daunting task in the proteomics field; it would be of great interest to use genomics tools for protein detection. One way to accomplish this is to use oligonucleotide-conjugated antibodies to bind to specific protein targets, and to monitor conjugated-oligonucleotide levels rather than to measure protein levels directly. In this report we describe a simple method for preparing oligonucleotide-conjugated antibodies and discuss this method’s application in oligo extension reaction (OER) for multiplex protein detection. Conjugation is based on strain-promoted alkyne-azide cycloaddition (the Cu-free click reaction), in which the antibody is activated with a dibenzocyclooctyne (DBCO) moiety and linked covalently with an azide-modified oligonucleotide. The reaction condition and purification process were optimized to achieve maximum yield and best performance in the functional test. The OER assay employs a pair of antibody binders (two antibodies, each conjugated with its own oligonucleotide) developed for each protein target. The two oligonucleotides contain a six-base complementary region at their 3′ prime ends to allow annealing and extension by DNA synthesis enzymes to form a DNA template. The template is then detected by qPCR on the Biomark HD system. Distinct oligonucleotide sequences are assigned to different antibody binders to enable multiplex protein detection. When tested using recombinant proteins, some antibody binders, such as those specific to CSTB, MET, EpCAM and CASP3, had an estimated limit of detection (LOD) of about 0.06 pg/mL and a dynamic range of ≥5 logs. These antibody binders were used in multiplex protein detection in single cells using the C1™ system. The results in individual cells showed the expression of similar protein levels for CSTB and CASP3, but highly varied protein levels for EpCAM, CCNB1 and MUC1. This simple method for the preparation of oligonucleotide-conjugated antibodies is essential for the development of affordable multiplex protein assays, which has the potential to accelerate proteomics research. Citation Format: Haibiao Gong, Ilona Holcomb, Aik Ooi, Xiaohui Wang, Daniel Majonis, Marc Unger, Ramesh Ramakrishnan. A simple method to prepare oligonucleotide-conjugated antibodies for multiplex protein detection. [abstract]. In: Proceedings of the Fourth AACR International Conference on Frontiers in Basic Cancer Research; 2015 Oct 23-26; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2016;76(3 Suppl):Abstract nr B18.
Acute Varicocele Revealing Renal Cancer
Authors: Yassine El Abiad, Abdelmounaim Qarro
Journal: New England Journal of Medicine (2016)

A 65-year-old man presented to the urology clinic with swelling in the area of the left testicle that had started 4 weeks earlier. Examination of the scrotum revealed an enlarged varicose vein along the left spermatic cord, and abdominal palpation revealed a mass in the right flank.
Abstract IA08: Functional long noncoding RNAs in lung cancer
Authors: Sven Diederichs
Journal: Cancer Research (2016)

Abstract The majority of the human genome is transcribed into non-protein-coding RNA. Hence, RNA is also the primary product of the cancer genome. We have defined the ncRNA expression landscape of lung, breast and liver cancer providing a comprehensive expression map of over 17000 long ncRNAs and discovering new lncRNAs associated with cancer whose molecular and cellular functions we are currently elucidating exploiting our custom siRNA library targeting 638 tumor-associated lncRNAs. The nuclear lncRNA MALAT1 was one of the first lncRNAs associated with cancer: it is associated with metastasis development in lung cancer. However, its high abundance and nuclear localization have hampered its functional analysis. To uncover its functional importance, we developed a MALAT1 knockout model in human lung tumor cells by genomically integrating RNA destabilizing elements site-specifically into the MALAT1 locus. This approach yielded a 1000-fold silencing of MALAT1 providing a unique loss-of-function model. Proposed mechanisms of MALAT1 action include regulation of splicing or gene expression. In lung cancer, MALAT1 does not alter alternative splicing but regulates gene expression inducing a signature of metastasis-associated genes. Consequently, MALAT1-deficient cells are impaired in migration and form fewer tumor nodules in a mouse xenograft model. Encouraged by this discovery of the essential function of MALAT1 in lung cancer metastasis, we analyzed whether MALAT1 could serve as therapeutic target for an Antisense oligonucleotide (ASO). Notably, MALAT1-ASO treatment prevented metastasis formation after tumor implantation. Thus, targeting MALAT1 with ASOs provided a therapeutic approach to prevent lung cancer metastasis with MALAT1 serving as both, predictive marker and therapeutic target. In summary, ten years after the discovery of the lncRNA MALAT1 as a biomarker for lung cancer metastasis, our loss-of-function model unraveled the active function of MALAT1 as a regulator of gene expression governing hallmarks of lung cancer metastasis. Citation Format: Sven Diederichs. Functional long noncoding RNAs in lung cancer. [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer: Mechanisms to Medicines ; 2015 Dec 4-7; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2016;76(6 Suppl):Abstract nr IA08.
Immunologic Recovery Following Consolidation with 90Yttrium Ibritumomab Tiuxetan (Zevalin®)-BEAM and Autologous Stem Cell Transplantation for Transformed B Cell Non-Hodkgin’s Lymphoma
Authors: Marielle J Wondergem, Theresia M Westers, Otto Visser, Josee M Zijlstra, Sonja Zweegman, Martine ED Chamuleau
Journal: Blood (2014)
Treatment of polycythaemia vera.
Authors: L SZUR, A W GOOLDEN
Journal: BMJ (1966)

Immune sera produced in horses or other animals are also limited in use, for as well as bearing a risk of enhancing the tumour they may damage normal organs such as the kidneys.'6Nevertheless, such methods have been widely used and encouraging results in terms of remissions have been reported.I7 18More recently so-called adoptive immunity with sensi- tized cells of human or animal origin has been advocated.The patient is given a lethal dose of radiation, and then the destroyed, immunological apparatus is re-established by the injection of new cells, which may be sensitized against the tumour's antigens.'It may be possible to overcome the reaction of the grafted cells against the host (secondary disease) either with drugs' or by the prior establishment in adult human donors of immunological tolerance to the recipient.It is generally agreed that it is not possible to make even newborn animals tolerant to all the transplanta- tion antigens of so different a species as man.'2E. J. Delorme and P. Alexander" have used sensitized sheep lymph-node cells to depress the growth rate of primary sarcomas induced by a carcinogen in the rat.They encountered anaphylaxis in some of the animals after three or four injections of sheep cells.It seems likely that antibodies will be produced to such cells and that their destruction will put an end to the treatment.Although the evidence for specific antigens against spontan- eous cancers in animals is unsatisfactory, some tumours in man might yet be found suitable for immunotherapy.More attention should be paid to one tumour-chorionepitheliomafor it should be susceptible to immune destruction.It is on the one hand fortunate that this tumour responds so well to chemotherapy and on the other hand unfortunate that no animal analogue of chorionepithelioma appears to exist.If immunotherapy is ineffectual against chorionepithelioma, then the case for using it against other cancers in man is weak.
TRANSIENT NEW-ONSET ATRIAL FIBRILLATION IS ASSOCIATED WITH POOR CLINICAL OUTCOMES IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION
Authors: Jin Wi, Dong-Ho Shin, Jung-Sun Kim, Byeong-Keuk Kim, Young-Guk Ko, Donghoon Choi, Myeong-Ki Hng, Yangsoo Jang
Journal: Journal of the American College of Cardiology (2015)
Early Neoplasias of the Gallbladder and Bile Duct: An “Unstable” Biliary Epithelium?
Authors: J.  Goh, B.  Kelleher, E.  Clarke, J.  C.  O’Keane, P.  MacMathuna
Journal: Endoscopy (2003)

Benign tumours of the biliary tree are rare. In particular, only anecdotal cases of intraductal villous adenomas have been reported. The polyp-cancer sequence has not been observed in the biliary epithelium, in contrast to the paradigm of colorectal carcinogenesis. This report presents the case of a 64-year-old woman with a past history of cholelithiasis who had two early neoplasias involving the biliary epithelium: an adenocarcinoma in situ of the gallbladder and a common bile duct (CBD) villous adenoma with high-grade dysplasia. The tumours presented 4 years apart. The clinical features and combined radiological, cytological, and surgical modalities leading to the diagnosis of intraductal villous adenoma are presented. The endoscopic ultrasound (EUS) characteristics of villous adenoma of the CBD are described.While the prognosis on both occasions appears excellent following curative resections of both tumours detected at an early stage, it is possible that further neoplasia involving the biliary tree may recur. There are currently no data on optimal surveillance modalities. It may be hypothesized that the gallbladder and biliary epithelium share a similar mechanism for carcinogenesis to that observed in the colonic adenomacarcinoma sequence.
PD-1 Signaling Has a Critical Role in Maintaining Regulatory T Cell Homeostasis; Implication for Treg Depletion Therapy By PD-1 Blockade
Authors: Takeru Asano, Yuriko Kishi, Yusuke Meguri, Takanori Yoshioka, Miki Iwamoto, Yoshinobu Maeda, Hideo Yagita, Mitsune Tanimoto, John Koreth, Jerome Ritz, Ken-Ichi Matsuoka
Journal: Blood (2015)
Reply
Authors: Natasha T. Snider, Bishr M. Omary
Journal: Hepatology (2013)

We thank Dr. French for his comments and questions about our study on the role of the ecto-nucleotidase CD73 in mouse liver Mallory-Denk body (MDB) formation.1 CD73 is expressed in multiple tissues, including the lung, heart, brain, kidney, liver, and the immune system.2 Although formation of extracellular adenosine is considered its primary function, CD73 also may act in a number of other ways independent of its enzymatic role.3 As Dr. French pointed out, our findings that CD73−/− mice are resistant to MDB formation is somewhat counterintuitive, given our initial observation that the MDB-susceptible mouse strain (C57BL/6J) is characterized by having lower CD73 mRNA and protein levels under basal conditions compared to the MDB-resistant C3H/He strain. However, we also showed that after 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) treatment there was a near complete loss of cell surface CD73 (AMPase) activity, but only a 60% decrease in overall CD73 activity (measured biochemically after tissue lysis). This observation, together with our findings of DDC-induced loss of plasma membrane CD73 in isolated hepatocytes, illustrates the complex nature of CD73 regulation in this model of liver injury. Therefore, the subcellular distribution (organellar versus plasma membrane) and regulation (such as glycosylation changes and enzymatic activity) of CD73 during hepatocellular injury are likely a more important determinant of hepatocyte injury than the overall CD73 expression levels. Furthermore, the MDB resistance in CD73−/− mice also may be immune-related, given the known major role of CD73 in regulating inflammatory and immune responses.4 For example, in absence of CD73 to catalyze the final and irreversible step in the conversion of extracellular adenosine triphosphate (ATP) to adenosine, the ATP levels in the vicinity of damaged and dying cells may significantly increase. This can accelerate the clearance of damaged cells by promoting phagocytosis by way of a number of mechanisms.5 Altered purinergic signaling on other immune cell types, such as regulatory T cells,6 also may alter the course of liver injury progression in CD73−/− mice. In summary, resistance to MDB formation in CD73−/− mice likely is related to a number of hepatocyte-intrinsic and -extrinsic mechanisms. Generation of mice with targeted deletion of CD73 from specific cell types should help resolve many outstanding questions pertaining to the functions of this enzyme in the liver. Natasha T. Snider, Ph.D. M. Bishr Omary, M.D., Ph.D. Department of Molecular & Integrative Physiology University of Michigan Medical School Ann Arbor, MI
Natural IgG antibodies as therapeutic agents for carcinoma and melanoma
Authors: Stephanie Brandlein, Nicole Schatz, Miriam Eckstein, H. Peter Vollmers
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

2128 

Natural or innate immunity is the first line defence against cancer. Antibodies play a major role in these processes and the majority of these germ-line coded antibodies are pentameric IgMs. Several of these natural antibodies have already been successfully used in clinical trials and for definition of new cancer targets. Natural immunity is also the bridge to immunological memory, resulting in affinity maturated IgG antibodies. We used the human hybridoma technology to screen cancer patients in a huge study on the humoral immune response for tumor-specific IgGs. Interestingly, we were able to isolate not only many cancer specific IgM antibodies, but also several tumor-reacting IgGs. We show in this study that these monomeric immunoglobulins show specific binding to carcinoma and melanoma cells, inhibit proliferation and induce apoptosis, similar to the already characterized natural IgMs. However, when sequenced, all found IgGs are not affinity-maturated. Biochemical studies on the antigens are underway. Natural IgG antibodies have been detected in sera, in quantities less than 1%, but so far, no one has been isolated, established and characterized in detail. This is the first report on natural monoclonal IgG antibodies with anti-cancer activity.
Current and Emerging Clinical Applications of Multispectral Optoacoustic Tomography (MSOT) in Oncology
Authors: Lacey R. McNally, Megan Mezera, Desiree E. Morgan, Peter J. Frederick, Eddy S. Yang, Isam-Eldin Eltoum, William E. Grizzle
Journal: Clinical Cancer Research (2016)

Abstract Accurate detection and characterization of cancers are key for providing timely intervention and effective treatments. Current imaging technologies are particularly limited when it comes to detecting very small tumors in vivo, i.e., very early cancers or metastases, differentiating viable tumor from surrounding dead tumor tissue, and evaluating tumor metabolism within tissue. Optoacoustic imaging offers potential solutions to these imaging problems because of its ability to image optical absorption properties of both intrinsic tissue chromophores and exogenous contrast agents without the involvement of ionizing radiation. Optoacoustic imaging uses pulsed laser to induce localized thermoelastic expansion that generates acoustic waves detectable by an ultrasound transducer. To date, multispectral optoacoustic tomography (MSOT) has primarily been used in preclinical research; however, its use in translational and clinical research is expanding. This review focuses on current and emerging applications of optoacoustic imaging for molecular imaging of cancer using both exogenous and endogenous contrast agents and sheds light on potential future clinical applications. Clin Cancer Res; 22(14); 3432–9. ©2016 AACR.
Abstract P6-07-02: Bisphenol A treatment induces hyperplasia in primary and stem cell-generated mammary glands from pregnant mice
Authors: H Bouamar, F Zhang, X Gu, Q Dong, L Sun
Journal: Cancer Research (2018)

Abstract Breast cancer is a commonly diagnosed cancer of pregnancy. However, how endogenous and exogenous endocrine factors may contribute to the development of pregnancy-associated mammary tumorigenesis is not clear. There is growing evidence that mammary stem cells (MaSCs) may initiate neoplastic transformation when dysregulated in mouse models. We investigated the effect of the environmental endocrine disruptor bisphenol A (BPA) on mouse mammary gland morphology, epithelial cell composition, pre-neoplastic lesions, and the regenerative function of MaSCs. Pregnant FVB mice with GFP transgene on Day E8.5 were implanted with osmotic pumps that constantly release BPA at 0, 25 or 250 ng/kg/day for 28 days and the mice were euthanized one month after weaning. In agreement with the literature, we observed an abnormality of the morphology of the mammary gland after BPA treatment characterized by higher duct density and abnormal secondary and tertiary branching. Quantification of percent hyperplastic mammary ducts in H&amp;E-stained tissue slides revealed a significant increase of ducts with hyperplastic lesions after BPA treatment, particularly with the low dose. To investigate the effects of BPA treatment on MaSCs, we used enzyme digestion to isolate the CD24hi/CD49f+ luminal epithelial cells (also termed as colony forming cell or CFC) and the CD24+/CD49fhi basal epithelial cells (also termed as mammary repopulating unit or MRU) from mammary gland tissues by FACS and found no significant difference in percent of luminal or basal cell population after BPA treatment. Because the basal cells are enriched with MaSCs that can form mammospheres in suspension culture and subsequently form solid 3D organoids when cultured in Matrigel, we transplanted the solid 3D organoids into cleared mammary fat pads of syngeneic FVB mice and immune-compromised nude mice to examine how BPA treatment might alter MaSC function. Significantly, similar to the results from the primary mammary glands, the regenerated mammary glands by MaSCs from mice treated with the low dose of BPA showed increased duct density, secondary and tertiary branching, and a significantly greater number of hyperplastic lesions. Taken together, our study demonstrated that BPA exposure at very low dose could induce pre-neoplastic lesions in the mammary gland of pregnant mice, apparently by directly targeting MaSCs and implicates BPA as an exogenous endocrine factor that may promote pregnancy-associated mammary tumorigenesis. Citation Format: Bouamar H, Zhang F, Gu X, Dong Q, Sun L. Bisphenol A treatment induces hyperplasia in primary and stem cell-generated mammary glands from pregnant mice [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-07-02.
Profile of the public health nurse
Authors: V. M. Ohlson
Journal: JAMA (1966)

The role of the nurse continues to be a favored subject for social science research and a topic for debate and conjecture among the health professions. Although differences in role perception exist, a fairly constant public as well as professional image persist with respect to the nurse who works within the hospital, an image which permits her to function, at least in part, in a patient-care-centered capacity. The function of her counterpart in the community, the public health nurse, frequently is not so well known or understood. With the growing complexities of extended health services beyond hospitalization, a clarification of the role of the public health nurse is warranted. The nurse in the community is eager to work with the physician, the hospital nurse, and other related health personnel in coordinated planning for the provision and continuity of patient care. The two requests she makes of the physicians are to
Cardiac Lesions in Experimental Hypertension
Authors: R D MOORE, M D SCHOENBERG, S KOLETSKY
Journal: JAMA (1963)

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The prevention of tardive dyskinesia
Authors: G E Crane
Journal: American Journal of Psychiatry (1977)

The publication of numerous articles on tardive dyskinesia has had little effect on the excessive use of neurolepic drugs in psychiatric populations. If current prescribing patterns are not drastically changed, larger numbers of patients will be afflicted by conspicuous, sometimes disabling neurological side effects. The risk of permanent neurological disorder can be minimized by monitoring side effects and systematically reducing drug doses in hospitals, outpatient centers, and private practice. However, one should not underestimate the difficulty in implementing such a program in facilities that rely heavily on chemotherapy.