tbuckley/cabot-search huggingface dataset:
Abstract B23: Role of noncoding RNAs in regulating human papilloma virus-16 (HPV-16) induced oncogenesis in head and neck squamous cell carcinoma (HNSCC)
Authors: Malay Kumar Sannigrahi, Varinder Singh, Rajni Sharma, Naresh K. Panda, Madhu Khullar
Journal: Cancer Research (2016)

Abstract Background: HPV is an emerging risk factor for HNSCC, however, molecular mechanisms in HPV mediated HNSCC remains poorly delineated. Recent studies suggest that non-coding RNAs may play an important role in the aetiology of HNSCC. In the present study, we examined microRNAs involved in HPV-16 induced HNSCC. Material and Method: Tissue samples from HNSCC patients (n=300) were screened for HPV-16 using PCR based approach with consensus PCR primers (MY09/MY11, Gp5+/Gp6+), HPV16-specific PCR, HPV-16 E7 mRNA, immunohistochemistry (p16, p53 and pRB) and viral-load determination. In-silico approach was used to identify host miRNAs with HPV-16 mRNAs as putative target. Differential expression of identified miRNAs was determined by qRT-PCR in HPV-16 positive (UPCI:SCC090, CaSki, SiHa), HPV negative (UPCI:SCC116, HaCat) and transfected with HPV 16 full genome plasmid cell lines, and, HPV 16-positive/HPV-negative tissue samples. Putative targets of identified miRNAs were identified by bioinformatic approach and their mRNA levels were determined by qRT-PCR in HPV positive and negative cell lines, and tissue samples. Over-expression and inhibition studies with miRNA mimic and inhibitor were done to identify affected viral and host oncogenic pathways. Results: Total 32 HNSCC patients were found to be HPV-16 positive. We identified 10 miRNAs with HPV-16 as putative target. Among them hsa-miR-139-3p showed significant down-regulation in HPV-16 positive samples and cell lines compared to HPV negative controls. Using bioinformatics tools, hsa-miR-139-3p was found to target viral HPV-16 E1 and host HOXB6 gene. Transfection with hsa-miR-139-3p mimic resulted in significant down-regulation of HPV 16 early mRNA as well as its targeted genes in luciferase-3'UTR assay. Moreover, mimic transfected HPV-positive cell lines showed dysregulated MEK-ERK signaling pathway. Conclusion: Our results suggest hsa-miR-139-3p may be involved in patho-physiology of HPV-16 positive HNSCC as it deregulates expression of HPV oncogenic proteins and cell proliferation by targeting MEK-ERK signaling pathway. Citation Format: Malay Kumar Sannigrahi, Varinder Singh, Rajni Sharma, Naresh K. Panda, Madhu Khullar. Role of noncoding RNAs in regulating human papilloma virus-16 (HPV-16) induced oncogenesis in head and neck squamous cell carcinoma (HNSCC). [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 B23.
Alternative to the hospital: a controlled study
Authors: L I Stein, M A Test, A J Marx
Journal: American Journal of Psychiatry (1975)

The authors describe the evaluation of a treatment model that makes use of the community to help mentally ill patients acquire necessary coping skills. This approach is based on the assumption that deficiency in coping skills and aggressive dependency are primarily responsible for high readmission rates to mental hospitals and that coping skills and autonomy are best learned in the community, where the patient will be needing and using them. The treatment model is evaluated by comparing it with progressive in-hospital treatment and follow-up care. The results suggest that the model described can successfully treat patients with a high level of symptomatology in the community rather than in the mental hospital.
MFG-E8 Drives Melanoma Growth by Stimulating Mesenchymal Stromal Cell–Induced Angiogenesis and M2 Polarization of Tumor-Associated Macrophages
Authors: Kazuya Yamada, Akihiko Uchiyama, Akihito Uehara, Buddhini Perera, Sachiko Ogino, Yoko Yokoyama, Yuko Takeuchi, Mark C. Udey, Osamu Ishikawa, Sei-ichiro Motegi
Journal: Cancer Research (2016)

Secretion of the powerful angiogenic factor MFG-E8 by pericytes can bypass the therapeutic effects of anti-VEGF therapy, but the mechanisms by which MFG-E8 acts are not fully understood. In this study, we investigated how this factor acts to promote the growth of melanomas that express it. We found that mouse bone marrow-derived mesenchymal stromal cells (MSC) expressed a substantial amount of MFG-E8. To assess its expression from this cell type, we implanted melanoma cells and MSC derived from wild type (WT) or MFG-E8 deficient [knockout (KO)] into mice and monitored tumor growth. Tumor growth and M2 macrophages were each attenuated in subjects coimplanted with KO-MSC compared with WT-MSC. In both xenograft tumors and clinical specimens of melanoma, we found that MFG-E8 expression was heightened near blood vessels where MSC could be found. Through in vitro assays, we confirmed that WT-MSC-conditioned medium was more potent at inducing M2 macrophage polarization, compared with KO-MSC-conditioned medium. VEGF and ET-1 expression in KO-MSC was significantly lower than in WT-MSC, correlating in vivo with reduced tumor growth and numbers of pericytes and M2 macrophages within tumors. Overall, our results suggested that MFG-E8 acts at two levels, by increasing VEGF and ET-1 expression in MSC and by enhancing M2 polarization of macrophages, to increase tumor angiogenesis. Cancer Res; 76(14); 4283-92. ©2016 AACR.
Painful Cutaneous Nodule of the Jawline
Authors: Elaine Kunzler, Joshua Weaver, Christina Cernik
Journal: JAMA Dermatology (2016)

A woman in her 30s presented with a 3-year history of painful nodules on her lower extremities, neck, and jawline; her medical history included seasonal allergies, and she did not take any prescription medications. What is your diagnosis?
Abstract IA20: Moving CAR T cell therapy forward: CARs and armored CARs
Authors: Renier J. Brentjens
Journal: Clinical Cancer Research (2016)

Abstract T cells may be genetically modified to express chimeric antigen receptors (CAR) targeted to antigens expressed by tumor cells. We have developed this technology in the laboratory and translated this adoptive T cell approach in the clinic. Treatment of patients with CD19 targeted CAR T cells has resulted remarkable remission rates in relapsed B cell acute lymphoblastic leukemia (B-ALL). Specifically, based on currently updated clinical outcomes, we have achieved &amp;gt;85% CR rates in adult patients with relapsed B-ALL treated with CD19 targeted CAR T cells which far exceed historical expectations. Further, by deep sequencing analysis, most treated patients were MRD- after CAR T cell therapy. Significantly, remissions were observed in both patients with overt morphological residual disease at the time of therapy as well as in patients with only residual MRD+ disease. Clinical trials form other centers which confirm the presented clinical trial outcomes from our center will be reviewed. While overall generally well tolerated, we found that patients treated with CAR T cells in the setting of overt disease experienced a cytokine release syndrome (CRS) with associated fevers, hypotension, and mental status changes including overt seizures. In contrast, far more modest responses were seen in patients with relapsed chronic lymphocytic leukemia (CLL). The discordant clinical outcomes between B-ALL and CLL patients treated with CD19 targeted CAR T cells remains a subject of conjecture although the tumor microenvironment is a strong focus of further investigation. To this end, we will present novel data on a next generation of CAR T cells, termed “armored CARs” further genetically designed to overcome an immune suppressive tumor microenvironment through further genetic modification of CAR T cells. Promising preclinical studies utilizing these “armored CAR” T cell approaches and their role in future clinical trials will be discussed. Citation Format: Renier J. Brentjens. Moving CAR T cell therapy forward: CARs and armored CARs. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Integrating Clinical Genomics and Cancer Therapy; Jun 13-16, 2015; Salt Lake City, UT. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(1_Suppl):Abstract nr IA20.
Lyme disease: a neuropsychiatric illness
Authors: B A Fallon, J A Nields
Journal: American Journal of Psychiatry (1994)

Lyme disease is a multisystemic illness that can affect the central nervous system (CNS), causing neurologic and psychiatric symptoms. The goal of this article is to familiarize psychiatrists with this spirochetal illness.Relevant books, articles, and abstracts from academic conferences were perused, and additional articles were located through computerized searches and reference sections from published articles.Up to 40% of patients with Lyme disease develop neurologic involvement of either the peripheral or central nervous system. Dissemination to the CNS can occur within the first few weeks after skin infection. Like syphilis, Lyme disease may have a latency period of months to years before symptoms of late infection emerge. Early signs include meningitis, encephalitis, cranial neuritis, and radiculoneuropathies. Later, encephalomyelitis and encephalopathy may occur. A broad range of psychiatric reactions have been associated with Lyme disease including paranoia, dementia, schizophrenia, bipolar disorder, panic attacks, major depression, anorexia nervosa, and obsessive-compulsive disorder. Depressive states among patients with late Lyme disease are fairly common, ranging across studies from 26% to 66%. The microbiology of Borrelia burgdorferi sheds light on why Lyme disease can be relapsing and remitting and why it can be refractory to normal immune surveillance and standard antibiotic regimens.Psychiatrists who work in endemic areas need to include Lyme disease in the differential diagnosis of any atypical psychiatric disorder. Further research is needed to identify better laboratory tests and to determine the appropriate manner (intravenous or oral) and length (weeks or months) of treatment among patients with neuropsychiatric involvement.
Book: Dicing with Death: Chance, Risk and Health
Authors: Deborah Ashby
Journal: BMJ (2004)

Are there any BMJ readers who have not encountered statistics and statisticians at some point in their career? Most medical students, and many other health professionals, have learnt some statistics as undergraduates, and maybe more as part of their postgraduate training. If you have obtained a grant or published a paper, the chances are that some statistician will have acted as statistical consultant or referee, if not as collaborator and coauthor. If you prescribe drugs, you are relying on the many statisticians employed within the pharmaceutical industry, and those involved in the regulation of drugs. Have you ever wondered why statistics and statisticians are now such an integral part of medicine? What do statisticians do, when they are not performing emergency χ2 tests and last minute power calculations, transforming messy data into elegant analyses, or training the next generation of doctors? In fact, why did they get into that line of work in the first place? How did statistics ever develop as a subject, and when did people start using it to address health and medical problems?​problems?




Figure 1



Stephen Senn Cambridge University Press, £14.99, pp 264 ISBN 0 521 54023 2

Rating: ★★★★




If you need to calculate a confidence interval, interpret a logistic regression, or defend your choice of a fixed or random effects meta-analysis to a referee, this is not the book for you. There are many excellent textbooks about medical statistics on the market; my personal favourite is Altman's Practical Statistics for Medical Research (Chapman & Hall, 1991). But Dicing with Death is not just another statistics textbook. This is a book that explores the history and the intellectual challenge of the subject, the personalities who shaped it, and the fundamental questions with which they grappled. In this volume you will meet familiar statistical names such as Fisher, Pearson, Poisson, and Student, and others you may not so readily associate with statistics, such as Edmund Halley. You will grapple with Simpson's paradox, the Bayesian-frequentist debate, baptism data from the 17th century, and the earliest randomised trials. Moving to current developments, you will see meta-analysis and the MMR (measles, mumps and rubella) debate in their statistical-historical context. The remarkable achievement is that all of this, and much more, are in a slim paperback that is best read cover to cover.

Inevitably, given the scope of the book, there is some unevenness. I wanted more on Florence Nightingale, whose brief mention underplayed her contributions to statistics. A few sections are harder going than others, although asterisks are used to indicate these. And some of the jokes are truly dreadful, although most are apposite.

Stephen Senn has attempted to do for medical statistics what Stephen Hawking did for physics in A Brief History of Time (Bantam Press, 1988) and Simon Singh did for pure mathematics in Fermat's Last Theorem (Fourth Estate, 1997). I think he has succeeded.
Abstract B32: Inhibiting DNA methylation causes an interferon response in cancer via dsRNA including endogenous retroviruses
Authors: Katherine B. Chiappinelli, Pamela L. Strissel, Alexis Desrichard, Huili Li, Christine Henke, Benjamin Akman, Alexander Hein, Neal S. Rote, Leslie M. Cope, Alexandra Snyder, Vladimir Makarov, Sadna Budhu, Jedd Wolchok, Cynthia A. Zahnow, Taha Mergoub, Timothy A. Chan, Reiner Strick, Stephen B. Baylin
Journal: Cancer Research (2016)

Abstract DNA methyltransferase inhibitors (DNMTis) upregulate immune attraction, including the interferon response, in solid tumors. We now define viral defense signaling as one mechanism for this. In epithelial ovarian cancer cells DNMTis upregulate viral defense by cytosolic sensing of double-stranded RNA (dsRNA), triggering a Type I Interferon response, upregulation of downstream interferon response genes, and increased apoptosis. Knockdown of the dsRNA sensors TLR3 and MAVS and inhibition of the interferon alpha/beta receptor blunt the DNMTi induced dsRNA response. DNMTis cause apoptosis of cancer cells, which is partially rescued by inhibiting the interferon alpha/beta receptor. We observe upregulation and demethylation of hypermethylated endogenous retroviruses (ERVs) and overexpression of individual ERVs whose sense and anti-sense transcripts may be key candidates for triggering the above signaling. Overexpression of ERVs alone is sufficient to trigger an interferon response in the absence of DNMTis. Basal levels of ERV and viral defense gene expression significantly correlate in primary OC and basal expression of the viral defense signature separates primary TCGA samples for multiple tumor types into low versus high expression groups. In melanoma patients treated with an immune checkpoint therapy, high viral defense signature expression in tumors significantly associates with durable clinical response and DNMTi treatment sensitizes to anti-CTLA4 therapy in a pre-clinical melanoma model. We thus define a major mechanism for how DNMTis may induce cancer cells to increase immune attraction and possibly sensitize patients to immunotherapy. Experiments determining which Aza-upregulated molecules on tumor cells are necessary for attraction and activation of host immune cells are ongoing. Citation Format: Katherine B. Chiappinelli, Pamela L. Strissel, Alexis Desrichard, Huili Li, Christine Henke, Benjamin Akman, Alexander Hein, Neal S. Rote, Leslie M. Cope, Alexandra Snyder, Vladimir Makarov, Sadna Budhu, Jedd Wolchok, Cynthia A. Zahnow, Taha Mergoub, Timothy A. Chan, Reiner Strick, Stephen B. Baylin. Inhibiting DNA methylation causes an interferon response in cancer via dsRNA including endogenous retroviruses. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Sep 24-27, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2016;76(2 Suppl):Abstract nr B32.
The DNA Content of Tumor Cells. I. Polyps and Adenocarcinomas of the Large Intestine of Man
Authors: Stich, H. F., Florian, S. F., Emson, H. E.
Journal: JNCI Journal of the National Cancer Institute (1960)

Journal Article The DNA Content of Tumor Cells. I. Polyps and Adenocarcinomas of the Large Intestine of Man Get access H. F. Stich, H. F. Stich Saskatchewan Research Unit, National Cancer Institute of Canada, and Department of Pathology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar S. F. Florian, S. F. Florian Saskatchewan Research Unit, National Cancer Institute of Canada, and Department of Pathology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar H. E. Emson H. E. Emson Saskatchewan Research Unit, National Cancer Institute of Canada, and Department of Pathology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 24, Issue 2, February 1960, Pages 471–482, https://doi.org/10.1093/jnci/24.2.471 Published: 01 February 1960 Article history Received: 08 July 1959 Published: 01 February 1960
Abstract P5-08-47: Clinical outcome of pathological T1N0 breast cancer according to the hormone receptor and HER2 status and adjuvant therapy
Authors: E Tokunaga, S Akiyoshi, C Koga, Y Nakamura, K Taguchi, M Ishida, S Ohno
Journal: Cancer Research (2016)

Abstract Background: The outcome of T1N0 breast cancer is relatively good, however, a subpopulation of this stage has a high population of relapse. It is important to clarify the factors associated with the outcome in order to determine the adequate adjuvant systemic therapy for T1N0 breast cancer. Aims: To investigate the prognosis of pathological T1N0 (pT1N0) breast cancer by receptor (estrogen receptor; ER, progesterone receptor; PgR, human epidermal growth factor receptor 2; HER2) status and adjuvant systemic therapy, and thus to identify the factors associated with the outcome. Methods: Among 2164 women who underwent surgery for primary breast cancer in our department, 925 had pathological T1N0 tumors (130 T1a, 234 T1b and 561 T1c). The associations between clinicopathological characteristics, adjuvant therapy and relapse-free survival (RFS) were examined Results: Of 908 patients with known hormone receptor (HR; ER and PgR) and HER2 status, 675, 79, 64 and 90 had HR+/HER2-, HR+/HER2+, HR-/HER2+ and HR-/HER2- (triple negative; TN) tumors, respectively. The prognosis of patients with T1c tumors was significantly poorer than that of the patients with T1a and T1b tumors (5-year DFS of T1a, T1b and T1c: 97.5%, 97.9%, 94.5%, p=0.0201). HR+/HER2- subtype was significantly associated with better prognosis than other subtypes (5-year DFS: 96.9% vs. 93.6%, p=0.0194). Patients younger than 40 year old or older than 74 years old had significantly shorter PFS (p=0.0039). Lymphovessel invasion (ly), high histological grade (HG2, 3) were associated with poor outcome in all cohort (p=0.0026, p=0.0356). In HR-positive tumors, ly, high HG and omission of the adjuvant endocrine therapy were associated with shorter RFS (p=0.0009, p=0.0306 and p=0.0016, respectively). Adjuvant chemotherapy was not associated with RFS regardless of HR and HER2 status. However, in T1c with nuclear grade (NG) 3 tumors, use of the adjuvant chemotherapy was associated better prognosis. The prognosis of patients with HER2+ tumors was not significantly different among patients with or without trastuzumab in this cohort. Conclusion: In spite of the excellent prognosis of pT1N0 breast cancer, adjuvant endocrine therapy is important for patients with HR+ tumors. However, the use of adjuvant chemotherapy or trastuzumab did not significantly improve the prognosis. Thus, the indication of chemotherapy or anti-HER2 therapy should be determined in consideration of the several prognostic factors for pT1N0 breast cancer. Citation Format: Tokunaga E, Akiyoshi S, Koga C, Nakamura Y, Taguchi K, Ishida M, Ohno S. Clinical outcome of pathological T1N0 breast cancer according to the hormone receptor and HER2 status and adjuvant therapy. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-08-47.
Reply
Authors: Jing H. Ngu, Richard B. Gearry, Catherine A. M. Stedman
Journal: Hepatology (2012)

We thank Dr. Shariff and colleagues for their interest in our study1 and for their helpful comments. We are more than happy to provide further detailed information on our cohorts and results in relation to the risk of hepatocellular carcinoma (HCC) development in patients with autoimmune liver diseases (AiLD) as requested. As described in our previous epidemiological study,2 36% of our autoimmune hepatitis (AIH) cohort had histological evidence of cirrhosis at diagnosis, a rate comparable to most other population-based epidemiological studies. In addition, 20% of the AIH cohort had Metavir stage 3 fibrosis, and 44% had stage 2 or lower degree of fibrosis at diagnosis. As reported in our current study, 3 out of 130 AIH patients developed HCC during total follow-up of 1,156 years. This is equivalent to a crude annual incidence of 259 per 100,000 years or 0.3% per year. Mean duration to a diagnosis of HCC from AIH diagnosis was 25 years, and 2 out of 3 of them were cirrhotic from diagnosis. Interestingly, our HCC annual incidence is much lower than that reported by Yeoman and colleagues3 (annual incidence of 1.1%). The discrepancy is likely due to the difference in the group of cohorts that were studied, as their cohort may have been affected by the referral pattern to tertiary specialist centers with a higher proportion of their cohort (56%) having cirrhosis. In our primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) cohorts, 12% and 9%, respectively, had cirrhosis at diagnosis. The prevalence of PBC in Canterbury is low compared to AIH and PSC, and that reported from Europe or North America.4 Our small PBC cohort is certainly a potential explanation for not detecting any HCC during the study period as acknowledged and discussed in our article. The aim of our study was to examine the survival and risk of malignancy in unselected population-based cohorts compared to that of the general population. Our results demonstrated increased mortality in patients with AiLD and increased risk of malignancy in AIH and PSC patients. Future studies should investigate for factors that could predict cirrhosis, malignancy, poor response to treatment, and death so that tailored management strategies and surveillance plans can be devised. Jing H. Ngu M.B.C.H.B., F.R.A.C.P.* , Richard B. Gearry M.B.C.H.B., F.R.A.C.P., Ph.D.* , Catherine A. M. Stedman M.B.C.H.B., F.R.A.C.P., Ph.D* , * Department of Gastroenterology, Christchurch Hospital, New Zealand, University of Otago, Christchurch, New Zealand.