tbuckley/cabot-search huggingface dataset:
Abstract 3082: miRNA-10b promotes medulloblastoma proliferation and survival via Bcl-2.
Authors: Rekha Pal, Stephanie Greene
Journal: Cancer Research (2013)

Abstract Introduction: The role of microRNAs (miRNAs) in the pathology of medulloblastoma (MB), the most common malignant brain tumor in children, is being elucidated at present. miRNA expression profiling studies have revealed a number of miRNAs implicated in medulloblastoma initiation and progression by controlling the expression of various genes responsible for cell proliferation or cell death. The effect of miRNA-10b on MB growth and proliferation through transcriptional induction of Bcl-2, an anti-apoptotic cellular proto-oncogene and tumor promoter, was explored in this study. Methods: Assays were carried out using six established MB cell lines and 13 primary MB samples. A screening cancer-specific miRNA array identified miRNA-10b as highly expressed in MB compared to normal cerebellum. Real-time PCR showed that miRNA-10b is significantly up-regulated (42-100 fold) compared to the normal cerebellum in all MB cell lines. Two MB cell lines (DAOY and UW228) were transiently transfected with control miRNA, miRNA-10b inhibitor, and miRNA-10b mimic for 48 to 72 hrs. The transfected cells were subjected to RT-PCR, MTT, apoptosis, clonogenic assay, and western blot analysis. Results: Transfection of miRNA-10b inhibitor induced a significant down-regulation of miRNA-10b expression in the MB cell lines, while miRNA-10b mimic induced miRNA-10b expression as measured by RT-PCR. Down-regulation of miRNA-10b expression resulted in a significant down-regulation of mRNA and protein levels of Bcl-2 and Mcl-1, decreased proliferation (p ≤ 0.001) and induced apoptosis (p ≤ 0.001) as compared to control. Inhibition of miRNA-10B further blocked the colony-forming capability of MB cells (p ≤ 0.001). miRNA-10b mimic transfection exerted an opposite effect. Down-regulation of miRNA-10b resulted in abrogation of phosphorylation of Bcl-2 at Ser70, a site previously reported to be critical in inhibiting apoptosis. Analyses of miRNA-10b levels in 13 primary MB samples revealed that the 2 patients with high levels of miRNA-10b (more than 200-fold increase versus control) had multiple recurrences (4.5) and died within 5 years of diagnosis, compared with the 11 patients with low levels of miRNA-10b who had a mean of 1.2 recurrences and 40% long-term survival. Conclusions: In conclusion, our data indicate that miRNA-10b may act as an oncomir in MB tumorigenesis, and reveal a previously unreported mechanism with Bcl-2 as an important mediator of miRNA-10b activity in MB cell survival. Targeting of miRNA-10b may provide a novel therapeutic approach in the treatment of MB. Citation Format: Rekha Pal, Stephanie Greene. miRNA-10b promotes medulloblastoma proliferation and survival via Bcl-2. [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 3082. doi:10.1158/1538-7445.AM2013-3082
Abstract 868: Replication of melanoma GWAS hits and exploration of pleiotropic effects of cancer GWAS hits with melanoma risk in the PAGE study
Authors: Jonathan D. Kocarnik, Cara Carty, Yi Lin, Megan D. Fesinmeyer, Jeff Haessler, Charles Kooperberg, Ulrike Peters
Journal: Cancer Research (2011)

Abstract Introduction: As the most serious form of skin cancer, melanoma is a considerable public health burden. Genome wide association studies (GWAS) have successfully identified several loci important to melanoma susceptibility. Some of these loci have been associated with other cancers as well, similar to the pleiotropy previously demonstrated in the 8q24 and TERT regions. Such pleiotropy can highlight important regions and may help inform variant functionality. However, the potential pleiotropic effects of gene variants identified for other cancers have not been fully explored for melanoma. This study evaluates whether GWAS hits for melanoma, as well as hits for non-melanoma cancers, are associated with melanoma risk. Methods: We included 918 white melanoma cases and 4495 white controls in the Women's Health Initiative, which were genotyped as part of the Population Architecture using Genomics and Epidemiology (PAGE) study. We evaluated 8 single nucleotide polymorphisms (SNPs) previously shown to be associated with melanoma in GWAS as well as 175 SNPs previously shown to be associated with other cancers. These findings were mostly based on GWAS in Caucasian populations. We used logistic regression to evaluate the association between each SNP and melanoma risk, using an age-adjusted additive genetic model. Results: Of the 8 melanoma SNPs evaluated, 7 were statistically significantly associated with melanoma risk (p&amp;lt;0.05). These SNPs were rs1393350 (p=0.001), rs16891982 (p=3.34e-05), rs258322 (p=1.53e-9), rs4785763 (p=3.29e-4), rs7023329 (p=2.20e-5), rs910873 (p=2.38e-4), and rs4636294 (p=5.82e-5). For each of these significant SNPs, the association was in the same direction of risk as previously reported. The SNP that did not replicate was rs2284063 (p=0.38). Our analysis for pleotropic effects of other cancer GWAS hits did not yield any significant associations after adjustment for multiple comparisons (p=2.87e-4). The most significant SNP was rs710521 (p=0.006), previously associated with urinary bladder cancer. Conclusions: This preliminary analysis demonstrates that nearly all previously discovered melanoma SNPs replicated. Our analysis did not discover any non-melanoma cancer SNPs that are also associated with melanoma. The next step in this analysis will be to incorporate data from the other three PAGE studies: the Multiethnic Cohort (MEC), Epidemiologic Architecture of Genes Linked to Environment (EAGLE), and the CALiCo Consortium (see pagestudy.org). This will substantially improve the power of our pleiotropy analyses. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 868. doi:10.1158/1538-7445.AM2011-868
Co-targeting leptin and insulin-like growth factor I signaling: dramatic effects of epidermal growth factor receptor inhibitors on triple negative breast cancer cells.
Authors: NK Saxena, LT Smith, BB Knight, M Sharma, D Sharma
Journal: Cancer Research (2009)

Abstract Abstract #3044 Introduction: Obesity is an independent risk factor for breast cancer and obese breast cancer patients exhibit a higher risk for larger tumor burden, increased metastasis and poor response to endocrine therapy. Obesity affects breast carcinogenesis by autocrine and paracrine effects of adipocytokine leptin and IGF-1. We have previously shown that leptin induces growth stimulation of breast cancer cells by recruiting histone acetyltransferases and mediator complex to cyclin D1 promoter via activation of Stat3. In the present study, we found a novel bidirectional crosstalk between IGF-1 and leptin signaling that promotes invasion and migration of triple-negative (ER, PR, HER2 negative) breast cancer cells; MDA-MB-231, MDA-MB-468, MDA-MB-435 and HCC-1806.&amp;#x2028; Methods and Results: IGF-1 induced significant tyrosine phosphorylation of leptin receptor (Ob-Rb) and leptin induced tyrosine phosphorylation of IGF-1 Receptor (IGF-1R). Combined treatment of leptin and IGF-1 induced synergistic activation of both Ob-Rb and IGF-1R along with activation of Akt and ERK. Furthermore, IGF-1 and leptin synergistically transactivated epidermal growth factor receptor (EGFR) and induced proliferation of triple negative breast cancer cells. We also found that tyrosine phosphorylation of EGFR induced by combined treatment of leptin and IGF-1 was significantly inhibited not only by EGFR tyrosine kinase inhibitor, AG1478 but also with a broad-spectrum matrix metalloproteinase inhibitor, GM6001 indicating that leptin and IGF-1 induced EGFR transactivation is dependent on proteolytic release of EGFR ligands. Intriguingly, we also found that combined treatment of leptin and IGF-1 potently induced invasion of triple negative breast cancer cells in Matrigel invasion and quantitative Electric Cell-Substrate Impedance Sensing invasion assays. Inhibition of leptin and IGF-1 mediated EGFR activation using a highly potent, reversible inhibitor of HER1/EGFR tyrosine kinase, erlotinib or dual epidermal growth factor receptor (EGFR)/human EGFR-2 (HER2) kinase inhibitor, lapatinib effectively inhibited leptin and IGF-1 induced invasion. Also, inhibition of EGFR activation using erlotinib and lapatinib reduced leptin- and IGF-1-induced migration of triple negative breast cancer cells.&amp;#x2028; Discussion: Taken together these data indicate a novel bidirectional crosstalk between leptin and IGF-1 signaling that transactivates EGFR and promotes metastatic properties, invasion and migration of triple negative breast carcinoma cells. Our novel findings indicate the possibility of using EGFR inhibitors erlotinib and lapatinib to counter the pro-cancerous effects of leptin and IGF-1 signaling in triple negative breast cancers. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3044.
Abstract 4013: S100A4 promotes cell migration and growth through focal adhesion kinase and Src mediated dual signaling pathways in pancreatic cancer cells.
Authors: Guoqiang Cai, Elizabeth H. Kerr, Meng Hu, Youfeng Yang, Donald J. Buchsbaum, William E. Grizzle, Qiang Ding
Journal: Cancer Research (2013)

Abstract BACKGROUD: Pancreatic cancer is one of the deadliest types of cancer. Activation and expression of focal adhesion kinase (FAK) and Src kinase is abnormally upregulated in pancreatic cancers. The results of clinical trials targeting either Src or FAK by inhibitors are largely unknown. S100A4 is a calcium-binding protein and aberrant S100A4 expression is an independent biomarker for poor outcomes of pancreatic cancer; however, the involved mechanism is unclear. METHODS: The effects of inhibitors on FAK and Src activation, and on cell migration and growth, were examined in MiaPaca2 and S2VP10 cell lines. To determine whether FAK and Src depend on each other or independently regulate pancreatic cancer cell phenotypes, the effects of FAK or Src mutant expression were determined. The role of S100A4 on FAK and Src activation was evaluated through loss/gain approaches. The association of S100A4 expression with FAK and Src activation was determined by immunostaining on human pancreatic cancer tissue sections. RESULTS: FAK and Src kinase inhibitors blocked activation in a dose dependent manner in both MiaPaca2 and S2VP10 cells. However, it required more inhibitor to inhibit either FAK or Src in S2VP10 cells. Blocking FAK (or Src) does not completely inhibit Src (or FAK) activation. This is confirmed by the finding that FAK mutant expression completely inhibited FAK activation, but not Src activation. Similarly, Src mutant expression did not inhibit FAK activation. Downregulation of S100A4 expression significantly decreased FAK and Src activation. Importantly, increased S100A4 expression is associated with increased FAK and Src activation in pancreatic cancer. CONCLUSIONS: These data support that the Src-FAK axis forms a dual signaling pathway, and each of them contributes independently to the aggressive pancreatic cancer cell phenotype. Also, these data support that S100A4 promotes the Src-FAK dual signaling pathway which possibly leads to a feed-forward loop facilitating pancreatic tumor progression. Citation Format: Guoqiang Cai, Elizabeth H. Kerr, Meng Hu, Youfeng Yang, Donald J. Buchsbaum, William E. Grizzle, Qiang Ding. S100A4 promotes cell migration and growth through focal adhesion kinase and Src mediated dual signaling pathways in pancreatic cancer cells. [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 4013. doi:10.1158/1538-7445.AM2013-4013
Abstract 995: Integrin-Linked Kinase localizes in the primary cilia to mediate Hedgehog signaling
Authors: Badia Barakat, Duc Vu, Luciano Martellotto, David N. Watkins, Gregory E. Hannigan
Journal: Cancer Research (2010)

Abstract The Hedgehog (Hh) signaling pathway is a highly conserved system for regulating metazoan development and cell fate. Integrin linked kinase (ILK) is required for proliferation of Hh-dependent neurons in the mammalian cerebellum, which also give rise to medulloblastoma, the most common childhood brain tumour. Sonic Hedgehog (SHh) binds to the Ptch transmembrane receptor, derepressing the Smo receptor to activate Hh signaling and key downstream targets such as Gli transcription factors. We find that SHh-induced osteogenic differentiation of C3H10T1/2 cells is blocked (&amp;gt;90% inhibition) by a small molecule ILK inhibitor, or by ILK-specific RNAi. SHh induces alkaline phosphatase (AP) activity in control 10T1/2 cells, but not cells transfected with ILK siRNA (&amp;gt;75% knockdown). Moreover we find that the small molecule ILK inhibitor suppresses SHh-induced differentiation in a dose-dependent manner, as effectively and to the same extent as the well-characterized selective Hh inhibitor, cyclopamine. Activation of Smo with the agonist, SAG, induces ILK-dependent AP induction in these cells, suggesting ILK acts downstream of Smo in the Hh pathway. SHh induction of the Gli1 transcription factor is also blocked by inhibiting ILK, suggesting ILK acts upstream of direct Hh targets. ILK inhibitor or siRNA suppresses constitutively activated Gli1 in medulloblastoma cells, derived from Ptch+/-:p53 compound heterozygote mice. In support of ILK involvment in Hh signaling, we have discovered a novel localization of ILK that indicates spatial proximity to Hh signaling molecules. The primary cilium is a microtubule-based organelle that is required for Hedgehog signaling, and we now find that ILK localizes in this structure. Using a selective ciliary marker, acetylated α-tubulin, we find that ILK localizes in the primary cilium along with components of the Hh pathway. Inhibition of ILK does not inhibit cilia formation, indicating that ILK is not involved in ciliogenesis. IFT proteins (eg. kinesin II motor subunit Kif3a), regulate both the assembly of, and the entry of Hh signaling proteins to, the cilium. Knockdown of Kif3a inhibits ciliogenesis and efficiently blocks SHh signaling, strongly suggesting the ciliary pool of ILK is critical for Hh signaling. Our work points to ILK as a novel therapeutic target in Hh-activated cancers. 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 995.
EFFECT OF NURSE-BASED MANAGEMENT OF HYPERTENSION IN RURAL WESTERN KENYA
Authors: Anirudh Kumar, Jemima Kamano, Kenneth Too, Deborah Tulienge, Charity Wambui, Evon Okidi, Carol Porter, Joyce Fitzpatrick, Sylvester Kimaiyo, Valentin Fuster, Rajesh Vedanthan
Journal: Journal of the American College of Cardiology (2016)
EFFECT OF CANDESARTAN AND METOPROLOL ON SUBCLINICAL MYOCARDIAL INJURY DURING ANTHRACYCLINE THERAPY: DATA FROM THE PREVENTION OF CARDIAC DYSFUNCTION DURING ADJUVANT BREAST CANCER THERAPY (PRADA) STUDY
Authors: Geeta Gulati, Siri Lagethon Heck, Jurgen Geisler, Morten W. Fagerland, Pavel Hoffmann, Berit Gravdehaug, Kjetil Steine, Anne H. Ree, Helge Rosjo, Torbjorn Omland
Journal: Journal of the American College of Cardiology (2016)
The efficacy of hyperbaric oxygen therapy (HBOT) in the treatment of pelvic radiation-induced late side effects
Authors: M. Inbar, D. Grisaru, G. Fishlev, J. Lessing, R. Almog, N. Gall, T. Safra
Journal: Journal of Clinical Oncology (2006)

18576 Background: The treatment of pelvic malignancies (uterine, cervix, rectum, etc) often include radiation. Radiation-induced late side effects (longer than 3 months) are developed in 5–10% of those patients. We wanted to investigate the efficacy of hyperbaric oxygen therapy (HBOT) in the management of those patients. Methods: Thirteen women were evaluated. The primary cancer sources were: cervix (7), vagina (2), uterus (2), rectum (1) and bladder (1). All patients were treated with a full pelvic dose of radiotherapy. Eight patients also underwent post-radiation surgery (4 post-hysterectomy, 1 post-colectomy, 1 post-vaginectomy, 1 post-cystectomy and 1 post-exanteration). Eleven patients suffered from pelvic pain, 7 from chronic cystitis (including 2 with vesico-vaginal fistulas), 7 had chronic proctitis (including 2 with recto-vaginal fistulas), 3 had long-standing vaginal ulcers, and one presented with a long-standing open skin wound following surgery. All patients underwent imaging studies and biopsies to rule out active malignant disease, and all received HBOT 100% oxygen, at 2 absolute atmospheres, for 90 minutes (2ATA 90 min). Results: The mean patient age was 61 years (range 32–88). The mean time between completion of radiation therapy and onset of symptoms was 32 months (range 4–60). The patients received an average of 27 HBOTs (range 16–40). Twelve patients reported improvement in pelvic pain, bladder and bowel symptoms and decrease in vaginal discharge. One patient developed lung metastasis and another developed pelvic recurrence. No patient reported side effects associated with HBOT. Conclusion: HBOT appears to be safe and effective in the management of pelvic radiation-induced late side effects, such as soft tissue necrosis (skin and vagina), cystitis, proctitis and fistulas. No significant financial relationships to disclose.
Abstract 475: Delineation of a cellular hierarchy in lung cancer reveals an oncofetal antigen expressed on tumor-initiating cells
Authors: Marc I. Damelin, Kenneth G. Geles, Maximillian T. Follettie, Ping Yuan, Michelle Baxter, Jonathon Golas, Shuguang Huang, John DiJoseph, Veronica Diesl, Carmen Behrens, Sung E. Choe, Carol Rios, Janet Gruzas, Latha Sridharan, Maureen Dougher, Arthur Kunz, Philip R. Hamann, Deborah Evans, Douglas Armellino, Kiran Khandke, Kimberly Marquette, Lioudmila Tchistiakova, Erwin Boghaert, Robert T. Abraham, Ignacio I. Wistuba, Bin-Bing S. Zhou
Journal: Cancer Research (2011)

Abstract Poorly differentiated tumors in non-small cell lung cancer (NSCLC) are refractory to chemotherapy and associated with short survival time. Here we integrate multiple experimental models with clinicopathological analysis of patient tumors to delineate a cellular hierarchy in NSCLC. We demonstrate that the oncofetal protein 5T4 is expressed on tumor-initiating cells and associated with worse clinical outcome in NSCLC. Coexpression of 5T4 and factors involved in the epithelial-to-mesenchymal transition was observed in undifferentiated but not in differentiated tumor cells. Despite heterogeneous expression of 5T4 in NSCLC patient-derived xenografts, treatment with an anti-5T4 antibody-drug conjugate resulted in complete and sustained tumor regression. Thus, the aggressive growth of heterogeneous solid tumors can be blocked by therapeutic agents that target a subpopulation of cells near the top of the cellular hierarchy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 475. doi:10.1158/1538-7445.AM2011-475
Radiologic imaging of over-the-scope-clips can be misunderstood: the “pooling sign”
Authors: P. Saxena, D. Abdollahian, A. Kompel, V. Singh, A. Lennon, M. Khashab
Journal: Endoscopy (2013)

The conventional treatment of gastrointestinal defects, including perforations, fistulas, and anastomotic leaks, is surgery, which is associated with significant morbidity and mortality [1] [2] [3] [4] [5] [6]. The over-the-scope clip (OTSC) (Ovesco Endoscopy AG, Tübingen, Germany) conforms to the shape of a cup after deployment ([Fig. 1] and [Fig. 2]) and provides more durable closure than standard clips because of its wider mouth and its ability to grasp larger amounts of tissue. Due to limited worldwide experience, radiologists may not be aware of its size and shape. We describe four cases in which the contrast pooling within the "cup" was misinterpreted as contained perforation.
P1012 ENHANCED LIVER FIBROSIS (ELF) TEST PERFORMS BETTER THAN HISTOLOGICAL PARAMETERS IN PREDICTING CLINICAL OUTCOMES IN PATIENTS WITH ADVANCED FIBROSIS DUE TO CHRONIC HEPATITIS C INFECTION
Authors: G.E. Dolman, A.M. Zaitoun, W.L. Irving, I.N. Guha
Journal: Journal of Hepatology (2014)
Familial Hyperinsulinism Caused by an Activating Glucokinase Mutation
Authors: Benjamin Glaser, Prebakaran Kesavan, Mozhgan Heyman, Elizabeth Davis, Antonio Cuesta, Andreas Buchs, Charles A. Stanley, Paul S. Thornton, M. Alan Permutt, Franz M. Matschinsky, Kevan C. Herold
Journal: New England Journal of Medicine (1998)

Spontaneous hyperinsulinemic hypoglycemia in adults is most frequently caused by sporadic, solitary pancreatic beta-cell tumors, whereas hyperinsulinemic hypoglycemia in childhood is commonly caused by generalized beta-cell dysfunction.1 Mutations in the beta-cell sulfonylurea-receptor (SUR1) gene or inward-rectifying potassium-channel (Kir6.2) gene were found in some patients.2–7 A distinct syndrome of hyperinsulinism with hyperammonemia was recently described,8,9 apparently caused by mutations in the glutamate dehydrogenase gene.10 However, many sporadic and familial cases of hyperinsulinism remain unexplained. Some may be due to somatic mutations in other genes, as suggested by reports of autosomal dominant familial hyperinsulinism that was . . .
Francis William Stanley Webb
Authors: P. Wright
Journal: BMJ (2012)

After initial posts at the London, Bath, and Poplar hospitals, Francis William Stanley Webb (“Bill”) succeeded in the MRCP in 1966. I was told by Clifford Wilson, professor of medicine at the London Hospital at the time, that Bill had achieved the highest marks in that examination. He trained in rheumatology at the Royal Postgraduate Hospital, Hammersmith and became senior registrar at the London Hospital. His rotation was to the Norfolk and Norwich Hospital. …