tbuckley/cabot-search huggingface dataset:
Abstract 4518: Prevalence of high-grade prostatic adenocarcinoma in a black African population
Authors: Emeka F. Nnakenyi, Ifeyinwa D. Nnakenyi, Okechukwu C. Okafor, Fred O. Ugwumba
Journal: Cancer Research (2018)

Abstract INTRODUCTION: Prostate cancer is the second most common type of cancer in men worldwide. Despite this, screening is currently disputed because studies in the western world have shown that more men die with the disease than from it. Black men have been documented to have a greater prevalence of prostate cancer which runs an aggressive course. Therefore, we aimed to determine the prevalence of high grade prostatic adenocarcinoma among Nigerian men. METHOD: This was a retrospective study of Nigerian men attending the urology clinic at University of Nigeria Teaching Hospital, Enugu, south-east Nigeria. Data on prostate histology were retrieved from the histopathology laboratory records for the last 5 years as thus: age, prostate diagnosis, gleason score. Histologic slides from core-needle biopsies had been reviewed by two Pathologists independently. If adenocarcinoma was diagnosed, Gleason system was used to grade the tumors, and a consensus was reached by both Pathologists. The data were analyzed with SPSS statistical software. RESULTS: Three hundred and forty-five (345) requests for histology on prostate biopsies were received, of which 118 (34.2%) were diagnosed with prostatic adenocarcinoma (PCa) at a mean age(sd) of 69(8.4) years. Minimum and maximum gleason scoring observed were 4 and 10. Gleason systemNo. of prostatic adenocarcinoma (%)Gleason score 2 – 6 (well differentiated PCa with excellent prognosis)22 (18.6%)Gleason score 7 (3+4 moderately differentiated PCa)19 (16.1%)Gleason score 7 (4+3 moderate to poorly differentiated PCa)11 (9.4%)Gleason score 8-10 (poorly differentiated with aggressive biologies)66 (55.9%) CONCLUSION: A high prevalence of high grade PCa was observed in this study, which are less likely to be cured. Therefore, early detection is crucial to prevent mortality. This may justify the need for prostate cancer screening in our African environment. Citation Format: Emeka F. Nnakenyi, Ifeyinwa D. Nnakenyi, Okechukwu C. Okafor, Fred O. Ugwumba. Prevalence of high-grade prostatic adenocarcinoma in a black African population [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4518.
Abstract 499: MicroRNA-411 downregulation promotes tumorigenesis and inhibits chemotherapy sensitivity by upregulating MLLT11 expression in human bladder cancer
Authors: Honglei Jin, Haishan Huang, Chuanshu Huang, Xiaohui Hua, Junlan Zhu
Journal: Cancer Research (2018)

Abstract Although several previous studies have reported the implication of various microRNAs (miRNAs) in regulation of human bladder cancer (BC) development, alterations and function of many miRNAs in BC carcinogenesis and anti-cancer therapy are not explored yet at present. Here, we screened 1900 known miRNAs and first discovered that miR-411 was one of major miRNAs that was downregulated in a n-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN)-induced BC mouse model. This miR-411 downregulation was also observed in human BC tissues and cell lines. The results from evaluating the relationship between miR-411 and patient survival in BC using the TCGA database also indicated that miR-411 was positively correlated with survival (&amp;gt;3 years). Our studies also showed that miR-411 inhibited tumorigenesis and increased chemotherapy sensitivity in human BC. Mechanistic studies revealed that overexpression of miR-411 repressed expression of ALL1-fused gene from the chromosome 1q (MLLT11) by binding to the 3′-untranslated region of MLLT11 mRNA, induced p21 expression, and caused cell cycle arrest at the G2/M phase, in turn inhibiting BC tumorigenic growth. Ectopic expression of miR-411 also increased the sensitivity of BC cells to the chemotherapeutic agents, whereas MLLT11 restoration in miR-411-overexpressing cells increased resistance to the chemotherapeutic agents. Citation Format: Honglei Jin, Haishan Huang, Chuanshu Huang, Xiaohui Hua, Junlan Zhu. MicroRNA-411 downregulation promotes tumorigenesis and inhibits chemotherapy sensitivity by upregulating MLLT11 expression in human bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 499.
Abstract 17040: Portico Stent Durability Driven from Anatomical Assessments of TAVR Patients
Authors: SaravanaKumar, GauravSatam, KristopherVietmeier
Journal: Circulation (2014)

Background: Transcatheter aortic valve replacement (TAVR) procedures are increasingly used to treat elderly patients with aortic stenosis. To ensure clinical safety, valve and stent frame durability is critical. Current FDA guidance requires stent frames to be durable to a minimum of 15 year equivalent life for safety. Hence, an understanding of the anatomy and its impact on stent frame durability is necessary. In this study, the steps taken to understand, quantify and test the Portico valve (St Jude Medical, St Paul, MN) stent frame is discussed. Methods: CT scans from representative TAVR patients (N = 52) were used to quantify deformation modes in the aortic anatomy. These scans were segmented and analyzed using 3Mensio Medical Imaging (3Mensio, Netherlands) and Solidworks (Dassault Systems, MA). The deformation modes were then translated to strain levels using finite element analysis (ABAQUS, Dassault Systems) to obtain test parameters for bench testing. Thirty samples were tested to these minimum stra...
Sequestration of T cells in bone marrow in the setting of glioblastoma and other intracranial tumors
Authors: Pakawat Chongsathidkiet, Christina Jackson, Shohei Koyama, Franziska Loebel, Xiuyu Cui, S. Harrison Farber, Karolina Woroniecka, Aladine A. Elsamadicy, Cosette A. Dechant, Hanna R. Kemeny, Luis Sanchez-Perez, Tooba A. Cheema, Nicholas C. Souders, James E. Herndon, Jean-Valery Coumans, Jeffrey I. Everitt, Brian V. Nahed, John H. Sampson, Michael D. Gunn, Robert L. Martuza, Glenn Dranoff, William T. Curry, Peter E. Fecci
Journal: Nature Medicine (2018)
Abstract 4148: Role of the photoreceptor gene, CRX (cone-rod homeobox) in pathogenesis of non-WNT, non-SHH medulloblastoma
Authors: Shalaka Masurkar, Aliasagar Moiyadi, Epari Sridhar, Rakesh Jalali, Neelam Shirsat
Journal: Cancer Research (2018)

Abstract Central nervous system (CNS) tumours are the second most common cancers diagnosed in children after leukemia and continue to be the leading cause of cancer-related mortality in children. Medulloblastoma (MB) is a highly malignant primary brain tumour that occurs in posterior fossa region of the brain. The current standard treatment regimen includes surgical resection, craniospinal irradiation and adjuvant chemotherapy. Although this has resulted in significant increase in survival, approximately one-third of medulloblastoma patients still die because of the disease. Genome-wide gene expression profiling studies have identified four molecularly distinct subgroups of medulloblastoma namely WNT, SHH, Group 3, and Group 4. Among the four subgroups, Group 3 patients exhibit highest incidence of metastasis and worst overall survival rates. Molecular mechanism underlying the pathogenesis of Group 3 medulloblastomas is not understood. Group 3 tumors often express retina photoreceptor-specific genes like CRX (Cone Rod Homeobox) which is a homeodomain transcription factor and it is essential for the normal development and maintenance of cones and rods cells of the retina. We have noted that this expression is also retained by the medulloblastoma cell lines like D425, D283 and D341 which have characteristics of Group 3 tumours. Downregulation of CRX in these cell lines brought about inhibition of cell proliferation and anchorage-independent growth as studied by soft agar colony formation assay. CRX gene, therefore, seems to act as an oncogene similar to OTX2, another homeobox gene overexpressed in medulloblastomas. Transcriptome profiling and CHIP-seq analysis is being carried out to identify genes regulated by CRX transcription factor to delineate the molecular mechanism underlying the oncogenic role of CRX in medulloblastoma pathogenesis. Citation Format: Shalaka Masurkar, Aliasagar Moiyadi, Epari Sridhar, Rakesh Jalali, Neelam Shirsat. Role of the photoreceptor gene, CRX (cone-rod homeobox) in pathogenesis of non-WNT, non-SHH medulloblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4148.
Abstract LB-388: New clinical diagnostic approach for miRNA quantification using the <i>Chlorella</i> virus DNA ligase
Authors: Iveta Hynstova, Tereza Mrackova, Michaela Adamcova, Barbora Dvorakova, Zlata Stastna, Ondrej Slaby, Milan Bartos, Viktor Ruzicka
Journal: Cancer Research (2018)

Abstract miRNAs have an immense potential to serve as diagnostic, prognostic and prediction biomarkers in the whole field of oncology. Their utilization in liquid biopsy as a non-invasive diagnostic tool is very promising as well. However, to our knowledge, no miRNA-based diagnostics is currently used in clinical laboratories. We believe the reason is simple - the lack of easy, fast, sensitive and reproducible measurement technology, which would have passed the strict clinical validation criteria. On this count we have optimized a very promising miRNA detection technique, utilizing the enzyme Chlorella virus DNA ligase (SplintR® ligase, New England Biolabs), for clinical use. This two-step method involves ligation of two adjacent DNA oligonucleotides hybridized to a miRNA target, followed by TaqMan probe real-time quantitative PCR (qPCR). We managed to reduce the total procedure time from previous 5 hours to 2 hours and 15 minutes maintaining the high sensitivity (1 amol/µl in original clinical sample) and large dynamic range (7 logs). Moreover, we enabled the use of two PCR detection chemistries - more cost-effective SYBR green or more specific TaqMan probe. Based on this optimized method we developed an assay for detection of miR-142-5p, potential marker of colorectal cancer. We measured miR-142-5p profiles in the real samples of whole blood, plasma and serum of healthy donors. The results showed an excellent correlation with the TaqMan qPCR assay and miREIA® immuno-based technology for absolute quantification of miRNA. We conclude, that using SplintR® ligase for miRNA detection is potentially useful for clinical diagnostics. This work was funded by the Ministry of Industry and Trade of Czech Republic, project No. CZ.01.1.02/0.0/0.0/16_084/0008832. Citation Format: Iveta Hynstova, Tereza Mrackova, Michaela Adamcova, Barbora Dvorakova, Zlata Stastna, Ondrej Slaby, Milan Bartos, Viktor Ruzicka. New clinical diagnostic approach for miRNA quantification using the Chlorella virus DNA ligase [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-388.
Stretch-Dependent Modulation of Contractility and Growth in Smooth Muscle of Rat Portal Vein
Authors: As’adZeidan, InaNordström, KarlDreja, UlfMalmqvist, PerHellstrand
Journal: Circulation Research (2000)

Abstract—Increased intraluminal pressure of the rat portal vein in vivo causes hypertrophy and altered contractility in 1 to 7 days. We have used organ cultures to investigate mechanisms involved in this adaptation to mechanical load. Strips of rat portal vein were cultured for 3 days, either undistended or loaded by a weight. Length-force relations were shifted toward longer length in stretched cultured veins compared with freshly dissected veins, whereas the length-force relations of unstretched cultured veins were shifted in the opposite direction. This occurred after culture either with or without 10% FCS to promote growth. The wet weight of loaded veins increased by 56% in the presence of FCS, whereas that of undistended control veins increased by 24%. No weight increase was seen in serum-free culture. The dry/wet weight ratio decreased during culture with FCS but was not affected by stretch. Electron microscopy revealed increased cell cross-sectional area in stretched relative to unstretched veins, ...
Abstract 13108: Socioeconomic Barriers to the Diagnosis of Peripheral Arterial Disease
Authors: Peter Chang, Kevin T Nead, Rahul Thakker, John P Cooke, Jeffrey W Olin, Nicholas J Leeper
Journal: Circulation (2013)

Objectives: To identify risk factors and barriers associated with the underdiagnosis of peripheral arterial disease (PAD). Background: PAD is a highly prevalent condition that is recognized as a co...
Abstract 250: Multiple lines of evidence make <i>ZDHHC3</i> a possible marker for breast cancer in African American women
Authors: Nicholas A. Kinney, Robin T. Varghese, Ramu Anandakrishnan, Harold R. Garner
Journal: Cancer Research (2018)

Abstract Rates of breast cancer mortality continue to be divided among race and ethnicity without a definitive explanation. Between the years 2005-2009 the racial disparity in breast cancer mortality caused about 9 extra death per 100 breast cancer cases in African American women compared to Caucasian women. In addition, young African Americans tend to have more aggressive forms of breast cancer. The source of this health disparity likely stems from a complex combination of mammography rate and frequency; segregation; socioeconomic status; and genetics. We contribute to what is known about genetics by investigating microsatellites - a type of repetitive DNA - and possible links to the breast cancer mortality gap. Microsatellites are understudied compared to single nucleotide polymorphisms and have the capacity to affect gene expression. We screen 33,854 microsatellites in germline DNA of African American women with and without breast cancer: four are statistically significant. We preform further analysis of genes harboring these microsatellites; the results reveal that ZDHHC3 is particularly interesting. Its location (3p21) is already linked to early invasive breast cancer. Kaplan-Meier analysis shows that ZDHHC3 alterations may be associated with poor breast cancer survival. Data from cBioPortal suggests that ZDHHC3 mRNA expression is lower in African Americans compared to Caucasians. These independent lines of evidence make ZDHHC3 a candidate for further investigation. Citation Format: Nicholas A. Kinney, Robin T. Varghese, Ramu Anandakrishnan, Harold R. Garner. Multiple lines of evidence make ZDHHC3 a possible marker for breast cancer in African American women [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 250.
Diagnostic Use of Serum Deoxyribonuclease I Activity as a Novel Early-Phase Marker in Acute Myocardial Infarction
Authors: YasuyukiKawai, MasahiroYoshida, KenichiroArakawa, TeruhikoKumamoto, NorihiroMorikawa, KatsuhikoMasamura, HiroshiTada, SachikoIto, HiroshiHoshizaki, ShigeruOshima, KoichiTaniguchi, HidekazuTerasawa, IsamuMiyamori, KoichiroKishi, ToshihiroYasuda
Journal: Circulation (2004)

Background— The delayed release of serum cardiac markers such as creatine kinase isoenzyme MB and equivocal early electrocardiographic changes have hampered a diagnosis of acute myocardial infarction (AMI) in the early phase after its onset. Therefore, a reliable serum biochemical marker for the diagnosis of AMI in the very early phase is desirable. Methods and Results— Serum samples were collected from the patients with AMI, unstable angina pectoris, stable angina pectoris, and other diseases. Levels of serum deoxyribonuclease I (DNase I) activity in the patients were determined. An abrupt elevation of serum DNase I activity was observed within approximately 3 hours of the onset of symptoms in patients with AMI, with significantly higher activity levels (21.7±5.10 U/L) in this group compared with the other groups with unstable angina pectoris (10.4±4.41 U/L), angina pectoris (10.8±3.70 U/L), and other diseases (9.22±4.16 U/L). Levels of the DNase I activity in serum then exhibited a marked time-dependent...
Abstract 1461: Targeting mitotic kinases in breast cancers in Latinas
Authors: Yainyrette Rivera-Rivera, Mihaela Marina, Jamie King, Miyoung Lee, Harold I. Saavedra
Journal: Cancer Research (2018)

Abstract African Americans and Latino women (Latinas) in the US have higher risks of developing molecular subtypes of breast cancer that associate with poor-prognosis, including hormone receptor-negative (HR-): triple-negative (ER-PR-Her2-), and Her2-positive breast cancer relative to whites. These women also present with higher-stage breast tumors relative to whites. We specifically study Puerto Rican women, a population in which breast cancers are the primary cause of cancer-related death, and who display a higher frequency of HR- breast tumors than other Latinas. We propose that chromosome instability (CIN) is a principal contributor to poor prognosis of breast cancers in African Americans and Latinas, since HR- breast cancers accumulate the highest CIN of all breast cancer subtypes. CIN in cancers correlates with poor clinical outcomes and centrosome amplification (CA) -defined as the presence of 3 or more centrosomes within a cell-, and defective mitosis are two principal drivers of CIN. Albeit CA correlates with invasion, metastasis, poor clinical outcomes, and HR- subtypes, molecular mechanisms responsible for CA in breast cancers are still unknown. We have identified MPS1 and NEK2 as centrosomes/mitotic kinases that drive CA/CIN in HR- breast cancer cells, and that can potentially be targeted to curb the malignant behavior of the most aggressive breast cancer subtypes affecting ethnic minorities. MPS1 and NEK2 are upregulated in HR- breast tumors and are co-overexpressed in several predictive signatures of poor prognosis subtypes and metastasis. Our preliminary data indicated that these kinases are overexpressed in over 60% breast cancers from Puerto Rican women and that they are exclusively co-upregulated in basal breast cancers. Our preliminary data also showed that these two mitotic kinases can significantly influence epithelial-to-mesenchymal transition (EMT) and invasion -activities never described for mitotic kinases. Also, although inactivating NEK2 suppresses S phase, inhibition of MPS1 reduces survival of breast cancer cells. Because inhibitors are available for MPS1 and NEK2, it would be feasible to target these kinases to combat metastatic HR- breast cancers. Our work will allow the identification of pathways influenced by mitotic regulators in breast cancer cells driving invasion and metastasis and will provide potential prognostic markers for high-risk breast tumors in various ethnic/racial groups, including African American and Latinas (including Puerto Rican women). Citation Format: Yainyrette Rivera-Rivera, Mihaela Marina, Jamie King, Miyoung Lee, Harold I. Saavedra. Targeting mitotic kinases in breast cancers in Latinas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1461.
Prostaglandin E2 Primes the Angiogenic Switch via a Synergic Interaction With the Fibroblast Growth Factor-2 Pathway
Authors: FedericaFinetti, SandraDonnini, AntonioGiachetti, LuciaMorbidelli, MarinaZiche
Journal: Circulation Research (2009)

Rationale: Prostaglandin (PG)E2 exerts temporally distinct actions on blood vessels, immediate vasodilatation, and long-term activation of angiogenesis. Objective: To study the mechanism of PGE2 induction of angiogenesis, we characterized its effect on fibroblast growth factor (FGF)-2 signaling in cultured endothelial cells and in ex vivo and in vivo assays of blood vessel formation. Methods and Results: Using Western blotting assay, we demonstrated that PGE2 induced upregulation of components of the FGF-2 pathway: FGF-2 protein, phosphorylation of FGF receptor type 1 (FGFR1), activation of FRS2α (FGFR substrate 2α), phospholipase Cγ, endothelial nitric oxide synthase, extracellular signal-regulated kinase 1/2, and the transcription factor STAT-3. Synergism between PGE2 and FGF-2 promoted endothelial cell proliferation and robust angiogenesis in vivo, in rabbit cornea and Matrigel assays. The magnitude of the angiogenic response to PGE2 was directly related to FGF-2 availability which determined the exten...
US government queries drug companies about alleged funding of Iraqi terrorists
Authors: Owen Dyer
Journal: BMJ (2018)

The US Department of Justice has made inquiries with at least three major drug makers—AstraZeneca, Roche, and Johnson & Johnson—relating to contracts they held in 2005-09 to supply Iraq’s health ministry with drugs and medical equipment.

The ministry was controlled at the time by the Mahdi Army, a Shiite militia, which used bribes or “commissions” paid by the drug makers to finance a roadside bombing campaign against US soldiers, says a lawsuit filed by the families and estates of dozens of US soldiers who were killed or injured by those bombs.1

That lawsuit was filed last October in a District of Columbia court against five companies and their subsidiaries. But the US justice department’s apparent interest in the case is new and came to light when the UK based AstraZeneca mentioned the suit in a securities filing at the end of July. Under “other legal matters,” the company referred to an “Iraq ministry of health litigation/anti-corruption probe.”

The justice department’s inquiry is “in connection with an anti-corruption investigation,” the company reported, and touches on “certain of the same matters alleged in the lawsuit.”

Days later, Johnson & Johnson made a similar statement in its quarterly filing to the Securities and Exchange Commission. A Roche …
Plasma-Advanced Oxidation Protein Products Are Potent High-Density Lipoprotein Receptor Antagonists In Vivo
Authors: GuntherMarsche, SasaFrank, AndelkoHrzenjak, MichaelHolzer, SabineDirnberger, ChristianWadsack, HubertScharnagl, TatjanaStojakovic, AkosHeinemann, KarlOettl
Journal: Circulation Research (2009)

Advanced oxidation protein products (AOPPs) are carried by oxidized plasma proteins, especially albumin and accumulate in subjects with renal disease and coronary artery disease. AOPPs represent an excellent novel marker of oxidative stress and their roles in the development of cardiovascular disease might be of great importance. Here, we show that in vitro-generated AOPP-albumin binds with high affinity to the high-density lipoprotein (HDL) receptor scavenger receptor class B type I (SR-BI). Already an equimolar concentration of AOPP-albumin to HDL blocked HDL association to SR-BI and effectively inhibited SR-BI-mediated cholesterol ester (CE) uptake. Interestingly, albumin extensively modified by advanced glycation end products (AGE-albumin), which is an established SR-BI ligand known to accumulate in renal disease, only weakly interfered with HDL binding to SR-BI. Furthermore, AOPP-albumin administration increased the plasma half-life of [3H]CE-HDL in control mice 1.6-fold (P=0.01) and 8-fold (P=0.0003...