tbuckley/cabot-search huggingface dataset:
Low Risk of Herpes Simplex Virus Infections in Neonates Exposed to the Virus at the Time of Vaginal Delivery to Mothers with Recurrent Genital Herpes Simplex Virus Infections
Authors: Charles G. Prober, Wayne M. Sollender, Linda Lew Yasukawa, Deborah S. Au, Anne S. Yeager, Ann M. Arvin
Journal: New England Journal of Medicine (1987)

We studied the risk of herpes simplex virus (HSV) infections in neonates exposed to HSV at the time of vaginal delivery to mothers with a history of recurrent genital HSV infections. None of 34 infants exposed to HSV type 2 acquired an HSV infection. On the basis of this sample, the 95 percent confidence limit for the theoretical maximum infection rate is 8 percent. Cord blood or blood obtained during the first two weeks of life was available from 33 of the 34 exposed, uninfected neonates. All 33 of the samples possessed demonstrable neutralizing antibody to HSV type 2, and 79 percent had titers above 1:20. These results were compared with those in a previously studied group of neonates with HSV infections; the latter infants were significantly less likely at the onset of symptoms to have demonstrable neutralizing antibody to HSV type 2 (P = 0.000148) or to have titers above 1:20 (P<0.00001). We conclude that given the low attack rate, empirical antiviral therapy is not warranted in all infants of mothers with recurrent genital HSV infection who are exposed to the virus in the birth canal. Our findings suggest that the presence and titer of neutralizing antibody to HSV contribute to the low attack rate. (N Engl J Med 1987; 316: 240–4.)
Abstract A63: Inhibition of ROCK signaling prevents breast cancer metastasis to human bone
Authors: Sijin Liu, Robert H. Goldstein, Ellen M. Scepansky, Michael Rosenblatt
Journal: Cancer Research (2009)

Abstract ROCK signaling plays a fundamental role in regulating cell morphology, adhesion and motility. Aberrant expression of ROCK is related to tumor metastases and correlates with poor clinical outcome. However, the molecular mechanisms responsible for ROCK-mediated effects and the potential utility of ROCK inhibition as a therapeutic target have not been fully investigated. Here, we show that ROCK expression is increased in metastatic human breast cancer (BrCa) cell lines and clinical mammary tumors compared to non-metastatic cell lines and tumors. Inhibition of ROCK activity, either by a specific ROCK inhibitor (Y27632) or ROCK-targeted siRNAs, reduces BrCa cell migration and proliferation in vitro. We evaluated the effect of ROCK inhibition on metastasis to bone in vivo using a novel “human BrCa metastasis to human bone” mouse model. Metastases to human bone cores (hBCs) were inhibited in Y27632-treated mice (5 out of 14, 36%) compared to control mice (8 out of 12, 67%), based on luminescent imaging. The overall frequency of metastasis to mouse skeleton in Y27632-treated mice was reduced by 36% compared to controls. Moreover, the mass of metastatic tumors in the mouse skeleton was diminished by 77% (P&amp;lt;0.05) in Y27632-treated mice. ROCK1 siRNAs also decrease the frequency of BrCa metastasis to hBCs and mouse skeleton, but to a lesser extent than Y27632. We demonstrate that ROCK's effects on tumor cell invasion/motility and growth may derive from regulating the actin-myosin cytoskeleton, modulating the c-Myc pathway by increasing the stabilization of c-Myc protein via phosphorylation, and targeting c-miRNAs. Coupled to increased c-Myc, expression of the c-Myc-regulated miR-17-92 cluster is shown here to be elevated in metastatic BrCa cells compared to non-metastatic cells, and diminished upon Y27632 treatment. Furthermore, blockade of miR-17 is shown to decrease BrCa cell invasion/migration in vitro and metastasis in vivo. Collectively, these findings suggest that augmented ROCK signaling contributes to BrCa metastasis in at least 3 ways, by 1) regulating the actin cytoskeleton and actin-myosin-dependent contractility; 2) targeting mRNAs controlled by the transcription factor c-Myc to potentiate cell growth and viability; and 3) modulating the expression of certain miRNAs, such as the c-Myc-regulated oncogenic miR-17-92 cluster. Inhibition of ROCK-mediated signaling appears to be a promising and potentially specific approach to suppress the occurrence of bone metastases in BrCa. Citation Information: Cancer Res 2009;69(23 Suppl):A63.
PREDICTORS AND RATES OF MORTALITY IN IMPLANTABLE CARDIOVERTER DEFIBRILLATOR RECIPIENTS IN THE CENTRAL MIDWEST
Authors: Indrajit Choudhuri, Randy S. Turkel, Maharaj Singh, Robyn L. Shearer, Abdur R. Ahmad, Bilal Omery, Arshad Jahangir, M. Eyman Mortada, Jasbir Sra
Journal: Journal of the American College of Cardiology (2016)
ME-13 * LOSS OF SOCS3 IN MYELOID CELLS DELAYS TUMOR GROWTH AND PROLONGS SURVIVAL IN A SYNGENEIC MODEL OF GLIOBLASTOMA
Authors: B. C. McFarland, M. P. Marks, A. L. Rowse, M. Gerigk, P. M. Walker, H. Qin, E. N. Benveniste
Journal: Neuro-Oncology (2014)

Glioblastoma (GBM), a particularly devastating type of brain tumor, remains a challenging and difficult disease to treat. Despite aggressive therapies, patients diagnosed with GBM have a median survival of 12-16 months. On a cellular level, GBM tumors are extremely heterogeneous, consisting of resident tumor cells, tumor initiating cells, infiltrating immune cells, endothelial cells, and other tumor associated stromal cells, which makes developing targeted therapies a challenge. In GBM, microglia (MG) and macrophages (MP) are the largest population of tumor-infiltrating cells. GBM tumor cells recruit MG/MP via the secretion of chemo-attractants; however, upon arrival at the tumor, the MG/MP adopt an anti-inflammatory phenotype, and in turn accidentally aide in tumor promotion through the secretion of various cytokines. We have previously determined that macrophages with deletion of Suppressor of Cytokine Signaling 3 (SOCS3), the negative regulator of Signal Transducer and Activator of Transcription 3 (STAT3), have an enhanced M1 (pro-inflammatory) response. Herein, we sought to determine the role of SOCS3 in MG/MP functionality in GBM. In this report, we utilized a conditional model in which SOCS3 deletion is restricted to the myeloid cell population. We found that deletion of SOCS3 in the myeloid cell population delays intracranial tumor growth and increases survival of mice bearing orthotopic glioma tumors. Intracranial tumors from mice with SOCS3 deficient myeloid cells have an increase in the number of infiltrating immune cells, including monocytes, neutrophils and macrophages. Lastly, SOCS3 deficient bone marrow derived macrophages display enhanced and prolonged expression of pro-inflammatory M1 cytokines (TNF-α, IL-6) when exposed to tumor cell conditioned medium in vitro. Therefore, loss of SOCS3 in MG/MP in the tumor promotes an inflammatory, immune response early and thus delays tumor growth. These preliminary findings highlight an important role of the STAT3/SOCS3 signaling axis in MG/MP in GBM tumors.
Case 29-2005
Authors: Richard P. Polisson, Jonathan T. Crocker, Peter R. Mueller, Nancy Lee Harris, Lyn M. Duncan
Journal: New England Journal of Medicine (2005)

A 68-year-old man noted a rash followed by periorbital swelling and muscular weakness. Several months before his hospital admission, he had had involuntary weight loss, and his physician had noted anemia. The results of an evaluation for gastrointestinal cancer were negative. Abdominal computed tomography disclosed a mass involving the spleen and retroperitoneum. A diagnostic procedure was performed.
Recurrent Severe Infections Caused by a Novel Leukocyte Adhesion Deficiency
Authors: Amos Etzioni, Moshe Frydman, Shimon Pollack, Israeli Avidor, M. Laurie Phillips, James C. Paulson, Ruth Gershoni-Baruch
Journal: New England Journal of Medicine (1992)

THE recruitment of neutrophils to sites of inflammation is initiated by the local production of bacteria-derived attractants, inflammatory cytokines, and other host-derived factors. These factors i...
Abstract 5361: Progesterone alters cell survival and cell death pathways in estrogen-induced mammary carcinogenesis
Authors: Arunkumar Arumugam, Rajkumar Lakshmanaswamy
Journal: Cancer Research (2010)

Abstract Breast cancer is one of the most frequent and common malignancy in women. The incidence of breast cancer is high in postmenopausal women and majority of these cancers are estrogen receptor positive. Epidemiological data suggests that estrogen plus progesterone hormone replacement therapy increases the risk of breast cancer in postmenopausal women. Further, estrogen alone therapy did not increase the risk instead decreased the risk of breast cancer in postmenopausal women. Till date the role of progesterone in breast cancer is not well understood. Our earlier studies using ACI rats have clearly demonstrated the significant role progesterone plays in the estrogen-induced mammary carcinogenesis. We now, aim to investigate the mechanisms by which progesterone promotes estrogen-induced mammary carcinogenesis in ACI rats. We chose to use the ACI rats as it is a good model to study hormone-induced mammary carcinogenesis. In brief, seven weeks old female ACI rats were divided into the following groups: 1) untreated control, 2) rats treated with 30 mg estradiol, 3) rats treated with 30 mg progesterone, 4) rats treated with 30 mg estradiol plus 30 mg of mifepristone (a progesterone inhibitor). All hormone treatments were given for 30 days by subcutaneous implants of silastic capsules. At the end of the treatment, mammary glands were excised and used for molecular analysis. Cell survival, cell death pathways, and hormone receptor status were analyzed using different molecular techniques. Expression patterns of mRNA and proteins involved in major cell survival and apoptotic pathways were significantly altered in response to progesterone inhibition. Our data demonstrates that progesterone plays a prominent role in regulating key regulatory pathways in estrogen-induced mammary carcinogenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5361.
OC-058 Bile Acid Malabsorption: “The Unusual Suspect”. A very Frequent Cause for Diarrhoea after Treatment for many different Cancer Types
Authors: F Phillips, A Muls, J Andreyev
Journal: Gut (2013)

<h3>Introduction</h3> Approximately 16,000 patients per year are left with a chronic change in bowel function and gastrointestinal symptoms following treatment for cancer. This can have a significant impact upon quality of life and even compromise on-going cancer therapy. Previous small studies focusing mainly on patients with gynaecological cancers suggest that bile acid malabsorption (BAM) may be an important cause of radiotherapy-induced diarrhoea. This retrospective study aims to elucidate the prevalence of BAM in patients referred to a specialist gastroenterology clinic which treats patients with consequences of cancer treatments. <h3>Methods</h3> Patients referred to our clinic are managed using a peer reviewed algorithm. If they report diarrhoea, defined as Bristol Stool Chart type 6–7, a routine referral for a SeHCAT (75-selenium homocholic acid taurine) scan is made to exclude BAM. BAM is diagnosed when the SeHCAT 7 day retention is &lt; 15% and is graded mild (10–15%), moderate (5–10%) and severe (&lt; 5%). <h3>Results</h3> Between 2009–2012, 262 patients were referred for a SeHCAT scan. 139 (53.1%) were male (median age 66, range 32–89) and 123 (46.9%) female (median age 61, range 20–86). 79 (37%) patients had been treated for gynaecological, 94 (44%) for urological, 41 (19%) for anorectal and 30 (11%) for upper gastrointestinal tract cancers. A further 18 (7%) were treated for other cancer types (breast, lung and haematological). BAM was diagnosed in 24 patients (25%) treated for urological cancers, with 17% (n = 4) having severe BAM. 46 patients (58%) treated for gynaecological cancers had BAM, severe in 57% (n = 26). BAM was diagnosed in 22 patients (54%) treated for anorectal cancers, with 55% having severe BAM (n = 12). In 15 patients (50%) treated for upper GI cancers, the majority (73%) had severe BAM (n = 11). For patients with other cancer types, BAM was diagnosed in 8 patients (44%) with severe BAM in 2 of these (25%). <h3>Conclusion</h3> The frequency of severe bile acid malabsorption and its impact on quality of life is poorly appreciated amongst those who treat cancer. BAM is a common problem in patients treated for a wide variety of cancers with a number of different treatment modalities. Given the effectiveness of dietary fat manipulation combined with a new generation of bile acid sequestrants, SeHCAT scanning should be a first line in investigating patients with diarrhoea after cancer therapies. <h3>Disclosure of Interest</h3> None Declared
OC-069 Mesalazine For Treatment Of Diarrhoea-predominant Irritable Bowel Syndrome (ibs-d): A Multi-centre, Parallel Group, Randomised Placebo Controlled Trial: Abstract OC-069 Table 1
Authors: C Lam, W Tan, M Leighton, J Williams, A Agrawal, S Sen, S Foley, M Rutter, A Ramadas, P Whorwell, A Montgomery, R Spiller
Journal: Gut (2014)

<h3>Introduction</h3> “Immune activation” has been described in the mucosa of IBS-D patients which Mesalazine (M) could suppress. Our main aim was to compare the effect of M versus placebo (P) on stool frequency. Secondary endpoints were abdominal pain, stool consistency and satisfactory relief of IBS symptoms. <h3>Methods</h3> All patients were required to have daily stool frequency of ≥3/day for more than 2 days/week for 2 weeks and stool consistency of ≥25% type 5–7 and ≤25% type 1–2 according to the Bristol Stool Form Scale. Subjects were randomised to either 2g M/ P for a week, to increase to 2 g twice/day for remaining 11 weeks if tolerated. All participants completed a 12-week stool diary. Since we expected M would require &gt;2 months exert its effect, all primary and secondary outcomes were based on the stool diary completed during week 11–12. Satisfactory relief of IBS symptoms was defined as answering ‘yes’ to weeks 11 and 12 of the stool diary <h3>Results</h3> 136 subjects with IBS-D, meeting the Rome III criteria, were randomised to the 2 groups. Mean (SD) age was 47.1 (13.5) years in P and 42.6 (15.2). Treatment compliance for P and M were similar, 59% and 58% respectively. Analysis by intention to treat showed M did not improve bowel frequency, abdominal pain and stool consistency compared to P during week 11–12. Treatment did not affect satisfactory relief of IBS symptoms, HAD, PHQ15 and EQ-5D VAS scores compared to P. See table below for results. <h3>Conclusion</h3> This study did not show any clinically meaningful benefit or harm of M compared to P in this group of IBS-D patients. We need better phenotyping/ biomarkers for IBS patients to allow targeting of effective treatments. <h3>Disclosure of Interest</h3> C. Lam: None Declared, W. Tan: None Declared, M. Leighton: None Declared, J. Williams: None Declared, A. Agrawal: None Declared, S. Sen: None Declared, S. Foley: None Declared, M. Rutter: None Declared, A. Ramadas: None Declared, P. Whorwell Grant/research support from: Danone, Almirall, Shire, Boehringer Ingelheim UK, Sucampo, Saliz, Chr-Hansen and Norgine, Consultant for: Danone, Almirall, Shire, Boehringer Ingelheim UK, Sucampo, Saliz, Chr-Hansen and Norgine, A. Montgomery: None Declared, R. Spiller Grant/research support from: Lessaffre, Ironwood, Consultant for: Almirall, Astellas, Danone and Sanofi, Conflict with: free drug for clinical trial from Norgine.
Changing Staphylococci and Staphylococcal Infections
Authors: Ove Jessen, Kirsten Rosendal, Per Bülow, Viggo Faber, Knud Riewerts Eriksen
Journal: New England Journal of Medicine (1969)

Abstract Clinical and bacteriologic findings in about 2000 cases of bacteremia illustrate the changes within the staphylococcal flora in Danish hospitals during the years 1957–66. The phage type complex 52, 52A, 80, 81, usually resistant to penicillin and streptomycin only, regressed with the increasing use of newer antibiotics. It was succeeded by a series of mutually related types of phage Group III, in which resistance to several antibiotics was acquired concomitantly with a stepwise blocking of susceptibility to phage, probably owing to epidemic phage activity. The latest members of the series were often methicillin resistant. The combined effects of lysogenization, transduction and selection affect not only phage type and antibiotic resistance but also properties more directly connected with pathogenicity, such as lipase production, which facilitates the development of boils, and enhances mortality in cases of bacteremia. Development of new staphylococcal types is accelerated in hospitals by abunda...
ABERRANT SPLICING OF A BRAIN-ENRICHED ALTERNATIVE EXON ELIMINATES TUMOR SUPPRESSOR FUNCTION AND PROMOTES ONCOGENE FUNCTION DURING BRAIN TUMORIGENESIS
Authors: M. Bredel, R. Ferrarese, G. R. Harsh, A. K. Yadav, E. Bug, D. Maticzka, W. Reichardt, A. P. Masilamani, F. Dai, H. Kim, M. Hadler, D. M. Scholtens, I. L. Y. Yu, J. Beck, V. Srinivasasainagendra, F. Costa, N. Baxan, D. Pfeifer, D. v. Elverfeldt, R. Backofen, A. Weyerbrock, C. W. Duarte, X. He, M. Prinz, J. P. Chandler, H. Vogel, A. Chakravarti, J. N. Rich, M. S. Carro
Journal: Neuro-Oncology (2014)

BACKGROUND: Tissue-specific alternative splicing is known to be critical to emergence of tissue identity during development, yet its role in malignant transformation is undefined. Tissue-specific splicing involves evolutionary-conserved, alternative exons, which represent only a minority of total alternative exons. Many, however, have functional features that influence activity in signaling pathways to profound biological effect. Given that tissue-specific splicing has a determinative role in brain development and the enrichment of genes containing tissue-specific exons for proteins with roles in signaling and development, it is thus plausible that changes in such exons could rewire normal neurogenesis towards malignant transformation. METHODS: We used integrated molecular genetic and cell biology analyses, computational biology, animal modeling, and clinical patient profiles to characterize the effect of aberrant splicing of a brain-enriched alternative exon in the membrane-binding tumor suppressor Annexin A7 (ANXA7) on oncogene regulation and brain tumorigenesis. RESULTS: We show that aberrant splicing of a tissue-specific cassette exon in ANXA7 diminishes endosomal targeting and consequent termination of the signal of the EGFR oncoprotein during brain tumorigenesis. Splicing of this exon is mediated by the ribonucleoprotein Polypyrimidine Tract-Binding Protein 1 (PTBP1), which is normally repressed during brain development but, we find, is excessively expressed in glioblastomas through either gene amplification or loss of a neuron-specific microRNA, miR-124. Silencing of PTBP1 attenuates both malignancy and angiogenesis in a stem cell-derived glioblastoma animal model characterized by a high native propensity to generate tumor endothelium or vascular pericytes to support tumor growth. We show that EGFR amplification and PTBP1 overexpression portend a similarly poor clinical outcome, further highlighting the importance of PTBP1-mediated activation of EGFR. CONCLUSIONS: Our data illustrate how anomalous splicing of a tissue-regulated exon in a constituent of an oncogenic signaling pathway eliminates its tumor suppressor function and promotes tumorigenesis. This paradigm of malignant glial transformation as a consequence of tissue-specific alternative exon splicing in a tumor suppressor, may have widespread applicability in explaining how changes in critical tissue-specific regulatory mechanisms reprogram normal development to oncogenesis. SECONDARY CATEGORY: n/a.
Abstract 999: Epidermal growth factor protects squamous cell carcinoma against cisplatin-induced cytotoxicity through increased interleukin-1β expression.
Authors: Chi-Ruei Huang, Jhen-Hong Yang, Wen-Chang Chang, Ben-Kuen Chen
Journal: Cancer Research (2013)

Abstract The expression of cytokines, such as IL-1β, and the activation of the epidermal growth factor receptor (EGFR) are crucial regulators in the process of carcinogenesis. The correlation between growth factor and activated cytokine signals in the control of tumor development is a critical issue to be clarified. In our study, we found that the IL-1β gene and protein expression were induced by EGF in squamous cell carcinoma. To clarify the mechanism involved in EGF-regulated IL-1β expression, we examined the transcriptional activity and mRNA stability of IL-1β in EGF-treated cells. We found that EGF induced the expression of IL-1β, and was mediated through transcriptional activation, but not through mRNA stability. The involvement of Akt and NF-κB signaling pathways in the EGF-induced IL-1β gene expression and promoter activity was confirmed by treating cells with Akt and NF-κB inhibitors, LY294002 and parthenolide, respectively. Using immunofluorescence staining assay, the EGF-stimulated nuclear translocation of NF-κB (p65) was inhibited by pre-treating cells with LY294002 and parthenolide. Furthermore, EGF increased the binding of NF-κB to the NF-κB binding site of the IL-1β promoter through the activation of the Akt/NF-κB pathway, which resulted in activating IL-1β promoter activity. The expression and secretion of IL-1β induced by EGF considerably reduced chemotherapeutic drug cisplatin-induced cell death. These results showed that EGF enhanced the expression of IL-1β, which was mediated by the Akt/NF-κB pathway. The activation of EGF signaling and increase of IL-1β contributed to chemotherapeutic resistance of cancer cells, suggesting that the expression of IL-1β may be used as a biomarker to evaluate successful cancer treatment. Citation Format: Chi-Ruei Huang, Jhen-Hong Yang, Wen-Chang Chang, Ben-Kuen Chen. Epidermal growth factor protects squamous cell carcinoma against cisplatin-induced cytotoxicity through increased interleukin-1β expression. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 999. doi:10.1158/1538-7445.AM2013-999