tbuckley/cabot-search huggingface dataset:
GON4L Drives Cancer Growth through a YY1–Androgen Receptor–CD24 Axis
Authors: Neeraj Agarwal, Garrett M. Dancik, Andrew Goodspeed, James C. Costello, Charles Owens, Jason E. Duex, Dan Theodorescu
Journal: Cancer Research (2016)

In principle, the inhibition of candidate gain-of-function genes defined through genomic analyses of large patient cohorts offers an attractive therapeutic strategy. In this study, we focused on changes in expression of CD24, a well-validated clinical biomarker of poor prognosis and a driver of tumor growth and metastasis, as a benchmark to assess functional relevance. Through this approach, we identified GON4L as a regulator of CD24 from screening a pooled shRNA library of 176 candidate gain-of-function genes. GON4L depletion reduced CD24 expression in human bladder cancer cells and blocked cell proliferation in vitro and tumor xenograft growth in vivo Mechanistically, GON4L interacted with transcription factor YY1, promoting its association with the androgen receptor to drive CD24 expression and cell growth. In clinical bladder cancer specimens, expression of GON4L, YY1, and CD24 was elevated compared with normal bladder urothelium. This pathway is biologically relevant in other cancer types as well, where CD24 and the androgen receptor are clinically prognostic, given that silencing of GON4L and YY1 suppressed CD24 expression and growth of human lung, prostate, and breast cancer cells. Overall, our results define GON4L as a novel driver of cancer growth, offering new biomarker and therapeutic opportunities. Cancer Res; 76(17); 5175-85. ©2016 AACR.
Multiple myeloma: 2016 update on diagnosis, risk‐stratification, and management
Authors: S. Vincent Rajkumar
Journal: American Journal of Hematology (2016)

Multiple myeloma accounts for approximately 10% of hematologic malignancies.The diagnosis requires ≥10% clonal bone marrow plasma cells or a biopsy proven plasmacytoma plus evidence of one or more multiple myeloma defining events (MDE): CRAB (hyper c alcemia, r enal failure, a nemia, or lytic b one lesions) features felt related to the plasma cell disorder, bone marrow clonal plasmacytosis ≥60%, serum involved/uninvolved free light chain (FLC) ratio ≥100 (provided involved FLC is ≥100 mg/L), or &gt;1 focal lesion on magnetic resonance imaging. Patients with del(17p), t(14;16), and t(14;20) have high‐risk multiple myeloma. Patients with t(4;14) translocation and gain(1q) have intermediate‐risk. All others are considered standard‐risk. Initial treatment consists of bortezomib, lenalidomide, dexamethasone (VRD). In high‐risk patients, carfilzomib, lenalidomide, dexamethasone (KRD) is an alternative to VRD. In eligible patients, initial therapy is given for approximately 3–4 months followed by autologous stem cell transplantation (ASCT). Standard risk patients can opt for delayed ASCT at first relapse. Patients not candidates for transplant are treated with Rd until progression, or alternatively, a triplet regimen such as VRD for approximately 12–18 months. After ASCT, lenalidomide maintenance is considered for standard risk patients especially in those who are not in very good partial response or better, while maintenance with a bortezomib‐based regimen is needed for patients with intermediate or high‐risk disease. Patients with indolent relapse can be treated with 2‐drug or 3‐drug combinations. Patients with more aggressive relapse require a triplet regimen or a combination of multiple active agents. Am. J. Hematol. 91:720–734, 2016. © 2016 Wiley Periodicals, Inc.
Isolation and Characterization of 2′-Amino-Modified RNA Aptamers for Human TNF<i>α</i>
Authors: Xinrui Yan, Xuwen Gao, Zhiqing Zhang
Journal: Genomics Proteomics & Bioinformatics (2004)

Abstract Human tumor necrosis factor α (hTNFα), a pleiotropic cytokine with activities ranging from host defense mechanisms in infection and injury to severe toxicity in septic shock or other related diseases, is a promising target for drug screening. Using the SELEX (systematic evolution of ligands by exponential enrichment) process, we isolated oligonucleotide ligands (aptamers) with high affinities for hTNFα. Aptamers were selected from a starting pool of 40 randomized sequences composed of about 1015 RNA molecules. Representative aptamers were truncated to the minimal length with high affinity for hTNFα and were further modified by replacement of 2′-OH with 2′-F and 2′-NH2 at all ribopurine positions. These modified RNA aptamers were resistant to nuclease. The specificity of these aptamers for hTNFα was confirmed, and their activity to inhibit the cytotoxicity of hTNFα on mouse L929 cells was determined. Results demonstrated that four 2′-NH2-modified aptamers bound to hTNFα with high affinity and blocked the binding of hTNFα to its receptor, thus protecting the L929 cells from the cytotoxicity of hTNFα. Oligonucleotide aptamers described here are potential therapeutics and diagnostics for hTNFα-related diseases.
Use of laboratory tests to monitor heavy drinking by alcoholic men discharged from a treatment program
Authors: M Irwin, S Baird, T L Smith, M Schuckit
Journal: American Journal of Psychiatry (1988)

Changes in blood test values from the time of discharge from an alcohol treatment program to 3-month follow-up were studied in two consecutive series of alcoholic men. The parallel combination of a percent increase in gamma-glutamyltransferase (GGT) of greater than or equal to 20%, in aspartate aminotransferase (SGOT) of greater than or equal to 40%, and in alanine aminotransferase (SGPT) of greater than or equal to 20% over discharge values was developed as a rule and then cross-validated to identify those alcoholic men who had resumed drinking at follow-up. Serial determination of these three test values in combination can be used to distinguish recovering alcoholics who remain abstinent from those who resume drinking.
Association and activation of Btk and Tec tyrosine kinases by gp130, a signal transducer of the interleukin-6 family of cytokines
Authors: T Matsuda, M Takahashi-Tezuka, T Fukada, Y Okuyama, Y Fujitani, S Tsukada, H Mano, H Hirai, ON Witte, T Hirano
Journal: Blood (1995)
Infectious ulcerative colitis resulting in incomplete Reiter’s syndrome
Authors: Jay Toshniwal, Romesh Chawlani, Mukesh Bang, Sachin Kale
Journal: Endoscopy (2015)

A 20-year-old man presented with a 3-week history of lower abdominal pain. He had self-limiting diarrhea for 3 days prior to this episode of pain. Findings from physical examination and laboratory tests were unremarkable. On ultrasound examination, an edematous sigmoid colon was noted. Colonoscopy revealed multiple large ulcers in the rectum and sigmoid colon ([Fig. 1]). On histopathological examination, these lesions were confirmed as infective colonic ulcers ([Fig. 2]). The patient was treated with oral antibiotics and became asymptomatic.
Assessing Evidence for Physician Orders for Life-Sustaining Treatment Programs
Authors: Susan W. Tolle, Alvin H. Moss, Susan E. Hickman
Journal: JAMA (2016)

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Breast feeding premature babies improves their heart function as adults, study shows
Authors: Jacqui Wise
Journal: BMJ (2016)

Breast feeding premature babies improves the structure and function of their heart in adult life, a study published in Pediatrics has found.1

Previous research has shown that, in adult life, the hearts of people who were born prematurely have smaller chambers, thicker walls, and reduced function.

Researchers at the University of Oxford, UK, followed up 102 people from an original cohort of 926 preterm born infants who had taken part in a randomised controlled trial of different postnatal milk feeding regimens from 1982 to 1985. In the initial …
Longitudinal follow-up of Zika virus RNA in semen of a traveller returning from Barbados to the Netherlands with Zika virus disease, March 2016
Authors: Chantal Reusken, Suzan Pas, Corine GeurtsvanKessel, Ramona Mögling, Jeroen van Kampen, Thomas Langerak, Marion Koopmans, Annemiek van der Eijk, Eric van Gorp
Journal: Eurosurveillance (2016)

We report the longitudinal follow-up of Zika virus (ZIKV) RNA in semen of a traveller who developed ZIKV disease after return to the Netherlands from Barbados, March 2016. Persistence of ZIKV RNA in blood, urine, saliva and semen was followed until the loads reached undetectable levels. RNA levels were higher in semen than in other sample types and declined to undetectable level at day 62 post onset of symptoms.
Phase Ib trial of AVL-292, a covalent inhibitor of Bruton's tyrosine kinase (Btk), in chronic lymphocytic leukemia (CLL) and B-non-Hodgkin lymphoma (B-NHL).
Authors: Jennifer R. Brown, Jeff Porter Sharman, Wael A. Harb, Kevin R. Kelly, Marshall T. Schreeder, John W. Sweetenham, Paul M. Barr, James M. Foran, Janice Lynn Gabrilove, Thomas J. Kipps, Shuo Ma, Susan Mary O'Brien, Erica Evans, Heather Lounsbury, Bruce A. Silver, Juswinder Singh, Kathryn Stiede, William Westlin, Steven Witowski, Daruka Mahadevan
Journal: Journal of Clinical Oncology (2012)

8032 Background: Btk supports activation, survival, and proliferation of malignant B cells in CLL and B-NHL. AVL-292 is an oral, potent (IC 50 &lt; 0.5nM), selective small molecule covalent inhibitor of Btk. Methods: Patients (pts) with previously treated CLL or B-NHL were administered AVL-292 in escalating cohorts of 125, 250, or 400 mg po QD using a 3+3 design in continuous 28 day cycles until progressive disease (PD) or toxicity. Key objectives were safety, DLT, MTD, PK, and Btk occupancy. Plasma AVL-292 levels were assessed by LC-MS-MS. Btk occupancy by AVL-292 was assessed by covalent probe assay in peripheral blood mononuclear cells. Results: 12 pts have enrolled (3 each at 125 and 250 mg and 6 at 400 mg: 5M/7F; median age 68 years, range 45-79; median 2.5 prior therapies, range 1-10) including 8 CLL (2 with 17p-, 2 with 11q22-, 2 with both 17p-/11q22-; 2 mutated IGHV, 5 unmutated IGHV, 1 missing) and 4 B-NHL (1 diffuse large B cell lymphoma (DLBCL); 1 follicular (FL); 2 marginal zone (MZL)). Median time on treatment is 65 days, range 28-158. Ten of 12 pts continue on treatment: 1 pt (DLBCL) discontinued for PD after 1 cycle and 1 pt (FL) for DLT (Gr 4 plts; 400 mg QD). No other DLTs or grade 4 adverse events (AEs) have occurred and MTD has not been reached. Most frequent AEs reported include transient diarrhea, rash/skin infection, URI, nausea, and fatigue. Gr 3 AEs include 1 atrial fibrillation (not drug related) and 1 ANC low (probably drug related). To date, 8 of 8 CLL patients have stable disease (SD) with median 28% decrease from baseline lymph node measurement (range 3-40% decrease). Six of 8 pts with CLL experienced increased ALC in cycle 1: median increase 89.5% (range 50-212%). Two of 4 NHL pts have SD (both MZL), 1 PD (DLBCL), and 1 not evaluable due to DLT (FL). Full Btk occupancy was achieved with dose levels ≥ 250 mg. Multiple dose PK exposure (AUC last ) was linear with no accumulation from Day 1 to 15. Conclusions: AVL-292 was well tolerated from 125-400 mg po QD and early efficacy analysis in CLL and B-NHL shows 10/11 efficacy evaluable pts with SD. Full Btk occupancy was achieved with ≥ 250 mg QD and PK was predictable with no accumulation. Dose escalation is ongoing and MTD cohort expansion is planned.
Multimedia: Brave New NHS?
Authors: J A Raeburn
Journal: BMJ (1999)

Jo Lenaghan


Institute for Public Policy Research, £7.50, pp 135 




ISBN 1 86030 065 0

———————

Rating: ★★★

None of us, least of all geneticists, should be denied the bitter sweet sapience prayed for by Robert Burns, “tae see ourselves as ithers see us.” The Institute for Public Policy Research report A Brave New NHS? anticipates the impact of genetics in the millennium and doesn’t pull its punches: “The NHS is sleep-walking into the future.” My specialty was under examination; I felt threatened and was ready for fight or flight.

Jo Lenaghan assembled this report by contacts with geneticists, a family doctor, the Genetic Interest Group, and a public health professor. The subject is topical, and this book fills a gap among the many recently published review papers and books.

Where are we in 1999? A national network of accredited genetic centres provides the opportunity to link genetic information to the advantage of the wider family (while preserving confidentiality). The centres are constrained by limited NHS funds and are unable to contribute sufficiently to the educational exercises needed to inform non-genetic colleagues such as family doctors. In addition to maintaining established services, geneticists grapple with new work such as the genetic element of the multidisciplinary provision for cancer genetic services.

Policy planners who wish to develop the genetic paradigm within the NHS have advantages over those abroad because of our primary care system, the regionally located genetic centres, developing interest in public health genetics, and several relevant advisory bodies (both national ones such as the Human Genetics Advisory Commission and independent bodies such as the Nuffield Council for Bioethics and the Genetic Interest Group).

This report is gloomy about the range of bodies but excited at the opportunities if activities are coordinated. By being independent and fairly neutral in handling the many genetic controversies and by reaching understandable and achievable conclusions, the Institute for Public Policy Research provides a sound and useful summary of the current state of genetics for non-experts. One conclusion of the report is that there must be more genetic work in primary care, backed up by genetic centres and particularly by genetic nurse specialists.

Four years ago, the distinguished editor of a high impact medical journal declined my invitation for him to speak at a meeting entitled “Genetics is the Core of Medicine.” He gave three reasons: he hated speaking, he knew nothing about the topic, and he didn’t agree with the proposition. After reading A Brave New NHS? he might wish to reconsider his decision.
Psychopathology and psychiatric diagnoses of World War II Pacific theater prisoner of war survivors and combat veterans
Authors: P B Sutker, A N Allain, D K Winstead
Journal: American Journal of Psychiatry (1993)

This study assessed current and long-term psychological and psychiatric sequelae of war trauma in World War II Pacific theater combat veterans, some of whom had been Japanese prisoners of war (POWs).A group of 36 POW survivors and a group of 29 combat veterans, all of whom had seen fierce fighting and heavy unit casualties, were compared approximately 40 years later on psychological instruments assessing psychopathology constructs, negative mood states, and symptoms of posttraumatic stress disorder (PTSD) and on the computer-administered National Institute of Mental Health Diagnostic Interview Schedule.Although similar in personal backgrounds and in having suffered catastrophic war trauma, the two groups differed in the severity and type of psychiatric symptoms and in the occurrence of psychiatric disorders. Anxiety and depressive disorders were common in both groups, but there were differences in the frequency of PTSD diagnoses. Among the POW survivors, 70% fulfilled the criteria for a current diagnosis and 78% for a lifetime diagnosis of PTSD, compared to 18% and 29%, respectively, of the combat veterans.The findings point to the persistent nature of symptoms thought to be residuals of extraordinary stress and the relation between severity of psychiatric sequelae and characteristics of the stressors.
The Use of Secox (Sorafenib, Oxaliplatin, Capcitabine) as the Treatment of Advanced Hepatocellular Carcinoma (HCC): A Single-Center Analysis
Authors: T. Yau, J. Chiu, Y.F. Tang, P. Chan, R. Leung, H. Wong, S.-T. Fan, R. Poon
Journal: Annals of Oncology (2012)
Prevention of Hepatitis B Virus Transmission by the Gastrointestinal Fibrescope
Authors: U. Seefeld, G. Bansky, M. Jaeger, M. Schmid
Journal: Endoscopy (1981)

In a prospective study we examined the efficacy of a standardized disinfection method in preventing the transmission of hepatitis B virus by the gastrointestinal fibrescope. Four HBsAg- and Dane particle-positive patients who had been endoscoped served as possible sources of hepatitis B virus infection. We cleaned the instrument with a 10 % aldehyde liquid and used it immediately thereafter in 10 HBsAg-negative patients. Eight of them were followed-up for 7 months after the endoscopic procedure. None of them showed serological evidence of an endoscopically transmitted hepatitis B virus infection. It is concluded that disinfection with an aldehyde liquid is effective in preventing the transmission of hepatitis B virus by the fibrescope.
Case 3-1966
Authors: Edwin P. Maynard, Wallace A. Jones
Journal: New England Journal of Medicine (1966)

Presentation of CaseA seventy-six-year-old woman was admitted to the hospital because of bleeding per rectum.She had been well until four years previously, when she entered another hospital because of pneumonia. At the time of discharge her family was informed that she had heart disease, with congestive failure, mild diabetes, diverticulosis and a "tumor of the bowel with spread to the liver." Subsequently, she remained bedridden at home, with the complaints of anorexia, fatigue and heat intolerance. Four months before admission black stools were passed, and she complained of nausea. Trimethobenzamide hydrochloride (Tigan), oxethazine (Oxaine) and kaolin and pectin . . .
The Molecular Basis of Genetic Diversity among Cytoplasms of Triticum and Aegilops. VIII. Mitochondrial RFLP Analyses Using Cloned Genes as Probes
Authors: Tom Terachi, Koichiro Tsunewaki', Koichiro Tsunewaki
Journal: Molecular Biology and Evolution (1992)

Restriction fragment length polymorphisms (RFLPs) among mtDNA digests of Triticum and Aegifops species have been analyzed by Southern blot hybridization with four cloned mitochondrial genes as probes.Three Triticum and 14 ( 16 sources, in total) Aegilops species have been studied.These represent the three wheat groups Einkorn, Dinkel, and Timopheevi and all six Aegilops sections (Polyeides, Cylindropyrum, Vertebra@ Sitopsis, Amblyopyrum, and Comopyrum) .Hybridization patterns of eight restriction-enzyme /probe combinations (BumHI-or HindIIIdigested mtDNAs probed with four mtDNA clones, each containing one of the four genes atpA, coxll, rrn18&5, or rrn26) were examined.With all of the probes used, mtDNA from one source of Ae. speltoides showed hybridization profiles identical to those of T. timopheevi, and mtDNA from Ae. searsii gave profiles identical to those of Ae. kotschyi.Otherwise, different hybridization profiles were found among all mtDNAs, giving 19 mtDNA samples classifiable into 17 different types.Based on the percentages of common fragments among all pairs of mtDNAs, a phylogenetic tree of mitochondrial genomes was generated by the UPGMA method.The resultant tree showed that the mitochondrial genomes of Triticum and Aegilops have differentiated into three major groups: ( 1) T. monococcum, (2) Ae.speltoides and polyploid wheats, and (3) all other species.The hybridization patterns also revealed differences in copy numbers of all mitochondrial genes, although the extent of polymorphisms differed with the different probes.Stoichiometric fragments of one accession often corresponded to substoichiometric fragments of other accessions, suggesting quantitative, rather than qualitative, differentiation of mitochondrial genomes among accessions.
Case 45-1986
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely, John R. Benfield, Eugene J. Mark
Journal: New England Journal of Medicine (1986)

Presentation of CaseA 64-year-old man was admitted to the hospital because of an infiltrate in the upper lobe of the right lung.There was a long history of wheezing, for which he took no medications, and of repeated respiratory tract infections. An abnormality in the right lung dated back at least 10 years, when an x-ray film of the chest showed patchy opacities and possible bronchiectasis in the posterior segment of the right upper lobe. Three years later another x-ray film of the chest (Fig. 1) again revealed disease in the posterior segment of the right upper lobe; consolidation . . .
SIRT1‐mediated transcriptional regulation of SOX2 is important for self‐renewal of liver cancer stem cells
Authors: Limei Liu, Chungang Liu, Qianzhen Zhang, Junjie Shen, Heng Zhang, Juanjuan Shan, Guangjie Duan, Deyu Guo, Xuejiao Chen, Jiamin Cheng, Yanmin Xu, Zhi Yang, Chao Yao, Maode Lai, Cheng Qian
Journal: Hepatology (2016)

Hepatocellular carcinoma (HCC) is a highly aggressive liver tumor containing cancer stem cells (CSCs), which participate in tumor invasion, therapeutic resistance, and tumor relapse leading to poor outcome and limited therapeutic options. Histone deacetylatase sirtuin 1 (SIRT1) has been shown to be up-regulated in human cancers; however, its role in liver CSCs is unknown. In this study, we explored the biological functions of SIRT1 in liver CSCs. Our data show that SIRT1 is highly expressed in liver CSCs and decreases during differentiation. In addition, high levels of SIRT1 predict a decreased probability of survival in patients with HCC. SIRT1 is responsible for the maintenance of self-renewal and tumorigenicity of liver CSCs, and overexpression of exogenous SIRT1 can restore self-renewal of non-CSCs. We demonstrated that SOX2 is a main downstream regulator of SIRT1-mediated self-renewal and tumorigenicity potential of liver CSCs. Mechanistically, SIRT1 regulates transcription of the SOX2 gene by way of chromatin-based epigenetic changes, which are dependent on DNA methylation. This effect is achieved by alternation of histone modification and interaction with DNA methyltransferase 3A, resulting in hypermethylation of SOX2 promoter. Furthermore, we demonstrated that insulin growth factor signaling plays an important role in maintaining SIRT1 expression through increased SIRT1 protein stability.These findings highlight the importance of SIRT1 in the biology of liver CSCs and suggest that SIRT1 may serve as a molecular target for HCC therapy. (Hepatology 2016;64:814-827).
Thermal Effect in Skin Carcinogenesis
Journal: JNCI Journal of the National Cancer Institute (1981)

Journal Article Thermal Effect in Skin Carcinogenesis Get access Victor E. Archer, M.D. Victor E. Archer, M.D. Rocky Mountain Center for Occupational and Environmental Health The University of UtahSalt Lake City, Utah 84112 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 67, Issue 5, November 1981, Page 994, https://doi.org/10.1093/jnci/67.5.994 Published: 01 November 1981