tbuckley/cabot-search huggingface dataset:
ATPS-66INVESTIGATING S6K1 INHIBITORS FOR TARGETING PTEN-DEFICIENT GLIOBLASTOMA
Authors: Kelli Ennis, Xizhi Feng, Catherine Gallo, David Plas
Journal: Neuro-Oncology (2015)

PTEN-inactivation in glioblastoma (GBM) triggers the hyperactivation of protein kinases, including mTOR and its downstream target, the ribosomal protein S6 kinase 1 (S6K1). Previous studies have demonstrated the potential efficacy of mTOR inhibitors for GBM therapy. We explored S6K1 inhibitors for potential cytotoxic effects in PTEN-deficient GBM cells. All S6K1 inhibitors were effective in reducing the phosphorylation of S6K1 substrates. However, analysis of the phosphorylation of the inhibitor-bound S6K1 revealed important differences: some S6K1 inhibitors induced the phosphorylation of inhibitor-bound kinase, while others had little evidence of this effect. Induced phosphorylation of the inhibitor-bound kinase has been termed inhibitor hijacking. Our analysis in GBM cells suggests that S6K1 inhibitor hijacking is correlated with induced proximity to the upstream kinase, mTORC1. Evidence of inhibitor hijacking was inversely correlated with cytotoxic activity. We propose selective development of S6K1 inhibitors that avoid the hijacking effect for counteracting oncogenic signals in PTEN-deficient glioblastoma.
Case 8-2014
Authors: Tracey A. Cho, Andrew S. Chi, Pamela W. Schaefer, David N. Louis
Journal: New England Journal of Medicine (2014)

A 29-year-old man was admitted to the hospital because of headache, vomiting, photophobia, diplopia, and stiff neck. He was born in Southeast Asia. Brain imaging showed diffuse leptomeningeal enhancement. Cultures were sterile. A diagnostic procedure was performed.
Stat Bite
Authors: Lynn Ries
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article Stat Bite: Breast Cancer Stage Distribution Get access Lynn Ries Lynn Ries Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 19, 4 October 1995, Page 1435, https://doi.org/10.1093/jnci/87.19.1435 Published: 04 October 1995
PWE-069 Factors Associated with Reported Pain During Colonoscopy: A Retrospective Study
Authors: N Rahman, F A Cuison, O Shabir, A Zaman, M A Zubir
Journal: Gut (2013)

<h3>Introduction</h3> Colonoscopy is generally perceived as being a painful procedure. Nonetheless, pain is a rather subjective experience for individuals and can be multifactorial. The aim of this study was to identify the predictors of pain during colonoscopy. <h3>Methods</h3> 1824 consecutive colonoscopies performed in 2010 were identified. Data was retrospectively collected on gender, patients’ medical co-morbidities, type and effectiveness of bowel preparation, medication used during the procedure, endoscopist’s performance and endoscopic findings such as presence of diverticular disease. Logistic regression analysis was used to identify independent predictors of pain during the procedure. <h3>Results</h3> Male patients were found to be less likely to develop pain during colonoscopy (odds ratio (OR) 0.43, 95% CI 0.35–0.53, p &lt; 0.001). Those who had any malignancy in the past (OR 0.69, 95% CI 0.49–0.97, p = 0.02) and previous abdominal surgery (OR 0.63, 95% CI 0.47–0.84, p = 0.02) were less prone to having pain. Better bowel preparation improved the comfort of the procedure (OR 0.67, 95% CI 0.54–0.85, p = 0.001) however those who used Moviprep as bowel preparation were more likely to complain of pain (OR 1.83, 95% CI 1.34–2.49, p &lt; 0.001). Higher dose of pethidine requirement was found to be associated with increase likelihood of reporting pain (OR 1.03, 95% CI 1.02–1.04, p &lt; 0.001) but no association was found with the use of midazolam or buscopan. High performance endoscopists were found to cause less pain (OR 0.35, 95% CI 0.27–0.46, p = p &lt; 0.001). The presence of diverticular disease showed a strong trend towards increasing probability of pain although it did not reach statistical significance (OR1.4, 95% CI 1.1–1.8, p = 0.07). Age and medical co-morbidities like rheumatological and neurological problems did not have any significant association. <h3>Conclusion</h3> Likelihood of having abdominal pain during colonoscopy was found to be associated with being female, having poor bowel preparation and the procedure being performed by non-high performing endoscopists. Patients with past history of malignancy were also noted to have less tendency of having pain. The association of higher dose of pethidine and reported pain was likely to reflect the need of larger doses in such situation. Interestingly, history of previous abdominal surgery did not increase the likelihood of reporting pain and in fact had the opposite effect. The reason for why patients who had Moviprep as bowel preparation were more likely to complain of pain is unknown and this may need to be explored in future studies. <h3>Disclosure of Interest</h3> None Declared.
Air Force Offers Science And Technologies to Help Fight Cancer
Authors: J. Mathews
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article Air Force Offers Science And Technologies to Help Fight Cancer Get access James Mathews James Mathews Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 20, 19 October 1994, Pages 1498–1499, https://doi.org/10.1093/jnci/86.20.1498 Published: 19 October 1994
CLASS I HISTONE DEACETYLASE INHIBITION REDUCES SUSTAINED ATRIAL FIBRILLATION AND REMODELING IN DOGS
Authors: Mitsuru Seki, Jeffery Powers, Jianhe Huang, Ryan LaCanna, Christine Varkas, Jeffrey Arkles, Joshua Cooper, Remus Berretta, Fabio Recchia, Vickas Patel
Journal: Journal of the American College of Cardiology (2016)
Abstract 5312: Mutational analysis of the tyrosine kinome in serous and clear cell endometrial cancers.
Authors: Meghan L. Rudd, Hassan Mohamed, Jessica C. Price, Mary Ellen Urick, Andrea J. O'Hara, Matthieu Le Gallo, Pedro Cruz, Suiyuan Zhang, James Mullikin, Maria J. Merino, Daphne W. Bell
Journal: Cancer Research (2013)

Abstract Endometrial cancers (ECs) arise from the inner epithelial lining of the uterus. At diagnosis, the majority of ECs are carcinomas of endometrioid, serous, or clear cell histologies, or an admixture of at least two of these histological subtypes. Serous and clear ECs are rare at presentation but contribute disproportionately to mortality from EC. Thus, there is an acute need for novel therapeutic approaches to treat serous and clear cell ECs. Small molecule inhibitors directed against tyrosine kinases have shown clinical efficacy in other types of cancer in which the target kinase is mutationally activated. Here, we used Sanger sequencing to systematically search for somatic mutations within 527 exons that encode the catalytic domains of 85 tyrosine kinases from 23 serous, 10 clear cell, and 5 mixed histology ECs. For mutated genes, we extended the screen to another 73 ECs (21 serous, 10 clear cell, 42 endometrioid). Genes that were mutated in both the primary and secondary screens were resequenced in a tertiary screen to search for mutations in all coding exons among the entire panel of 111 endometrial tumors. Overall, we uncovered nonsynonymous somatic mutations of ACK1, DDR1, and KDR in 5.4%, 3.6%, and 1% of ECs. Serous tumors had mutated ACK1, DDR1 and KDR in 2.3%, 4.5%, and 2.3% of cases. Clear cell tumors had mutated ACK1 in 5% of cases. Endometrioid tumors had mutated DDR1 in 2.3% of cases. Immunoblotting confirmed that ACK1 and DDR1 are endogenously expressed in endometrial cancer cell-lines. Eighty-seven percent (7 of 8) of ACK1 mutations and 50% (2 of 4) of DDR1 mutations are predicted to impact protein function. To our knowledge this is the first report of ACK1 and DDR1 mutations in endometrial cancer. Our findings warrant future studies to determine whether the ACK1 and DDR1 mutations uncovered here are pathogenic. Citation Format: Meghan L. Rudd, Hassan Mohamed, Jessica C. Price, Mary Ellen Urick, Andrea J. O'Hara, Matthieu Le Gallo, NISC Comparative Sequencing Program, Pedro Cruz, Suiyuan Zhang, James Mullikin, Maria J. Merino, Daphne W. Bell. Mutational analysis of the tyrosine kinome in serous and clear cell endometrial cancers. [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 5312. doi:10.1158/1538-7445.AM2013-5312
Idiopathic pulmonary fibrosis: securing a confident diagnosis for every patient
Authors: Mark G. Jones, Simon L.F. Walsh, Kirk D. Jones, Luca Richeldi
Journal: European Respiratory Journal (2016)

Almost half a century ago Liebow and Carrington [1] proposed their landmark framework to classify the idiopathic interstitial pneumonias (IIPs), a diverse group of diffuse parenchymal lung diseases of unknown aetiology. This classification approach has since informed the principal that in IIP histopathological pattern may have clinical implications including prognosis and treatment. Five subgroups were identified, the most frequent of which was termed "usual" interstitial pneumonia (UIP) and is the pattern which, in the absence of any identifiable cause, is diagnostic of the prototypic chronic progressive fibrotic lung disease idiopathic pulmonary fibrosis (IPF) [2]. Inconsistent UIP pattern on HRCT in patients with suspected IPF should not rule out possibility of an IPF diagnosis <http://ow.ly/YcVao>
MICRO RNA BASED STRATEGY FOR ENHANCING THE EFFECT OF ONCOLYTIC HSV-1 VIRUS THERAPY
Authors: Y. Ino, M. Ito, T. Todo
Journal: Neuro-Oncology (2014)

BACKGROUND: G47Δ is a third generation, genetically engineered, oncolytic herpes simplex virus type 1 (HSV-1) that is currently used in a clinical trial for patients with refractory glioblastomas. Genetic modifications in the γ34.5, ICP6 and α47 genes make G47Δ replicate selectively in tumor cells. Most tumor cell lines support the replication of G47Δ well and are susceptible to the therapy, but some cell lines are relatively resistant to oncolytic HSV-1. Micro RNA (miR) -199a-3p and miR-214 are reported to suppress wild type HSV-1 replication in murine cell lines. We investigated if these micro RNAs also have effect on the replication of onoclytic HSV-1. METHODS: Four human glioma cell lines were tested for the susceptibility for G47Δ, and A172 and T98G were found to be relatively resistant. Micro RNA expression levels were examined in real-time reverse transcription polymerase chain reaction (RT-PCR) assay, and both miR-199a-3p and miR-214 levels were high in these G47Δ resistant cell lines. Using tough decoy (TuD) microRNA suppression system, A172 and T98G with low miR-199a-3p and miR-214 expression were created. RESULTS: G47Δ replication and cytopathic effect were better in A172 and T98G miR-199a-3p low, miR-214 low cells than A172 and T98G cells which were transfected with control TuD, expressing original levels of miR-199a-3p and miR-214. CONCLUSIONS: These results suggest that expression level of some microRNA may have effects on oncolytic HSV-1 replication. Modulation of some specific micro RNA expression may enhance the anti-tumor effect of oncolytic HSV-1 therapy, and the micro RNA based strategy may be a useful tool to improve the efficacy of oncolytic HSV-1 therapy for malignant glioma. SECONDARY CATEGORY: n/a.
Abstract 2799: Regulation of tumor cell attachment, spreading and migration by the GPR4 receptor and related G protein pathways.
Authors: Calvin R. Justus, Li V. Yang
Journal: Cancer Research (2013)

Abstract The tumor microenvironment has a characteristic low pH due to inadequate blood perfusion, hypoxia, altered cellular metabolism, and inflammation. The effects of acidic pH on cancer progression are complex. It has been shown that low pH increases the metastatic spread of cancer by assisting in the degradation of extracellular matrix. Other studies show that acidic microenvironments decrease metastatic potential in B16F10 melanoma cells upon activation of the GPR4 receptor and also inhibit Akt activity in breast cancer cells. In this study we have investigated the attachment, spreading, and migration of B16F10 cells that have been genetically modified to express the GPR4 receptor at a high level (named B16F10/GPR4 cells). The results showed that upon stimulation of GPR4 in B16F10/GPR4 cells with low pH, cell spreading, membrane ruffling, and migration were significantly decreased. The phosphorylation levels of paxillin Y118 and focal adhesion kinase (FAK) Y397 following one-hour cell attachment were also decreased, and the spatial localization of the phosphorylated paxillin and FAK was substantially altered. Further tests were performed to identify the G-protein signaling pathway responsible for this effect. By using a G13 dominant negative construct or inhibiting Rho activation with C3 transferase (CT04) in B16F10/GPR4 cells, the cell spreading and membrane ruffling abilities were almost completely restored back to the level of B16F10/vector control cells, whereas the inhibition of the Gs and Gq pathways had little effect. These results suggest that activation of the GPR4 receptor and subsequently the G13/Rho downstream pathway are responsible for decreased cell attachment, spreading and membrane ruffling, which may cause decreased metastatic potential of B16F10/GPR4 cells found previously. Citation Format: Calvin R. Justus, Li V. Yang. Regulation of tumor cell attachment, spreading and migration by the GPR4 receptor and related G protein pathways. [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 2799. doi:10.1158/1538-7445.AM2013-2799
Expression of prostaglandin metabolizing enzymes in correlation with vitamin D receptor in benign and malignant breast cell lines and breast tissue and regulation of prostaglandin metabolism by calcitriol.
Authors: M Thill, D Fischer, S Becker, C Tim, K Diedrich, M Friedrich
Journal: Cancer Research (2009)

Abstract Abstract #6028 Backround: The antiproliferative effects of calcitriol [1,25(OH)2D3] make the biologically active form of vitamin D to a promising target in breast cancer therapy. It is well known, that these effects are mediated via the vitamin D3 receptor (VDR). Furthermore breast cancer is associated with inflammatory processes based on an upregulation of cyclooxygenase-2 (COX-2) expression, the prostaglandin E2 (PGE2) synthesizing enzyme. The PGE2 metabolizing enzyme, 15 hydroxyprostaglandin dehydrogenase (15 PGDH) is described as a tumor suppressor in cancer. First references suggest a correlation between vitamin D and prostaglandin metabolism through the impact of 1,25(OH)2D3 on the expression of COX-2 and 15 PGDH. Thus we evaluated the expression of COX-2 and 15 PGDH with VDR and the influence of calcitriol on COX-2 and 15 PGDH.&amp;#x2028; Materials and methods: The Expression of VDR, COX-2 and 15 PGDH in MCF10F, a human benign epithelial cell line and the breast cancer cell line MCF-7 was determined by real time PCR and western blot analysis. Furthermore, we determined mRNA level of COX-2 and 15 PGDH and VDR in healthy and malignant breast sample tissues. In addition we examined the effect of calcitriol on COX-2 and 15 PGDH mRNA levels.&amp;#x2028; Results: Although our data from real time pCR were divergent from those obtained from the western blot analysis, we showed, that COX-2 protein expression is increased in MCF-7 2-fold compared to MCF10F. These data were confirmed in breast cancer tissue samples, where COX-2 mRNA level increased to 1,44 in comparison to healthy tissues. No correlation of 15 PGDH was detected in both cell lines, but in malignant tissues 15 PGDH expression increase dramatically compared to healthy tissue samples. The expression of VDR we found differs in protein and mRNA level in benign and malign cell lines. VDR protein levels were inverse correlated to 15 PGDH expression and reveal that the benign tissue as well as the MCF10F cells have the highest VDR expression. Furthermore we demonstrated a downregulation of cyclooxygenase and an up-regulation of 15 PGDH by calcitriol.&amp;#x2028; Conclusion: We found a basically inverse correlation between VDR and 15 PGDH protein level expression. These findings suggest a possible link between VDR, associated target genes and the prostaglandin metabolism. The influence of calcitriol on COX-2 and 15 PGDH might lead to an additional novel pathway of calcitriol action mediating its antiproliferative effects in breast cancer and might open new therapeutic approaches in breast cancer therapy. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6028.
A Case–Control Study of HIV Seroconversion in Health Care Workers after Percutaneous Exposure
Authors: Denise M. Cardo, David H. Culver, Carol A. Ciesielski, Pamela U. Srivastava, Ruthanne Marcus, Dominique Abiteboul, Julia Heptonstall, Giuseppe Ippolito, Florence Lot, Penny S. McKibben, David M. Bell
Journal: New England Journal of Medicine (1997)

The average risk of human immunodeficiency virus (HIV) infection after percutaneous exposure to HIV-infected blood is 0.3 percent, but the factors that influence this risk are not well understood.
Abstract 3717: Randomized phase II trial of cladribine with or without immediate rituximab for newly diagnosed or previously treated hairy cell leukemia to eliminate minimal residual disease: Interim report
Authors: Robert J. Kreitman, Pierre Noel, Constance M. Yuan, Mark Raffeld, Maryalice Stetler-Stevenson
Journal: Cancer Research (2010)

Abstract Purine analogs including cladribine can induce complete remission (CR) in a high percentage of patients with previously untreated hairy cell leukemia (HCL), but late relapses are common and disease-free survival curves show no convincing evidence of cure. Many patients in CR after cladribine have minimal residual disease (MRD) which strongly expresses CD20, and the anti-CD20 Mab rituximab, particularly with a purine analog, can eliminate MRD to undetectable levels. To determine the potential benefit of adding rituximab to cladribine for initial or 2nd-line treatment of HCL, a randomized trial was begun in 150 HCL patients with 0-1 prior courses of cladribine requiring therapy. Patients receive cladribine 0.15 mg/Kg by 5 daily 2-hr i.v. infusions, and 8 weekly i.v. infusions of rituximab 375 mg/m2. Rituximab in half the patients is begun with the 1st dose of cladribine, and in the other half is delayed at least 6 months when MRD is detectable in blood. Endpoints include determining whether MRD rates are lower at 6 months with immediate rituximab, and whether blood MRD-free survival is longer when rituximab is delayed at least 6 months or begun with cladribine. HCL variant (HCLv) patients, known to respond poorly to initial cladribine alone, are not randomized and receive rituximab with cladribine. Bone marrow and blood are assessed for MRD by immunohistochemistry, PCR and flow cytometry at 1 and 6 months after cladribine. At this time 14 patients are enrolled, including 6 untreated and 8 with 1 prior course of cladribine, the latter group including 1 with HCLv. So far, the overall response rate is 100% with 10 (83%) CRs in 12 evaluable patients at 61-243 (median 202) days of follow-up. By 1 month, 0 of 5 patients after cladribine alone vs 5 (71%) of 7 after cladribine with immediate rituximab were MRD-free (p=0.028), including the patient with HCLv. Neutropenic fever was more frequent in patients receiving immediate rituximab, and was associated with both infusional reactions and reversible infections. We conclude that rituximab with cladribine can result in early clearing of MRD which is frequently present after cladribine alone. Additional accrual and follow-up is needed to determine whether simultaneous cladribine and rituximab can reduce MRD rates at 6 months, whether MRD-free survival might be longer or shorter with delayed rituximab, and whether rituximab added to cladribine for 1st or 2nd line treatment of HCL can prevent or delay clinical relapse. 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 3717.
P4-07-21: A Comparison of Two Methods for the Detection of Circulating Tumor Cells (CTCs) in Patients (pts) with Early and Metastatic Breast Cancer (BC): RT-PCR for Cytokeratin (CK) −19 mRNA Versus the CellSearch System.
Authors: E Politaki, S Agelaki, S Apostolaki, M Perraki, D Hatzidaki, ES Lianidou, D Mavroudis, V Georgoulias
Journal: Cancer Research (2011)

Abstract Background: Different methods are available for the detection of CTCs in pts with BC, however, the variable performance of these assays, the heterogeneity of CTCs, and the possible treatment-induced alteration of the markers evaluated, imply that no ideal method currently exists. We compared the efficiency of two methods to detect CTCs in pts with BC. Patients and Methods: Blood was obtained from 200 pts with early and 164 with metastatic BC before the start of adjuvant or first-line chemotherapy, respectively. Different aliquots of the same sample were evaluated by RT-PCR for CK-19 mRNA and by the CellSearch System. Blood samples were available after the end of adjuvant or first-line therapy in 99 and 93 pts, respectively. CTCs in 23 and 7.5 ml of blood were enumerated by CellSearch, in adjuvant and metastatic pts, respectively. Cut-off values of ≥1 and ≥2 CTCs/23 ml and ≥2 and ≥5 CTCs/7.5 ml were used. Twenty ml of blood were obtained for mRNA extraction in all RT-PCR experiments. Results: In early BC, 18.0% of samples were positive prior to therapy by RT-PCR and 37.0% (CTC≥1) and 16.5% (CTC≥2) by CellSearch. No significant correlation was shown for the detection of CTCs between methods. Overall (positive and negative) concordance was 62% for CTC≥1 and 73.5% for CTC≥2 (Chi-Square, p=0.161 and p=0.307). Post-chemotherapy, the positivity rate was 33.6% (CTC≥1) and 18.8% (CTC≥2) by CellSearch and 11.6% by RT-PCR (Spearman, R=-0.031, p=0.761). Overall agreement was 60.6% (CTC≥1) and 71.4% (CTC≥2) (Chi-Square, p=0.771 and p=0.708). In the metastatic setting, 37.8% of the samples were positive by RT-PCR, and 50% (CTC≥2) or 32.3% (CTC≥5), by CellSearch (Spearman, R=0.373, p=0.0001). Overall agreement was 70.0% for CTC≥5 (Chi-Square, p=0.0001). Post-chemotherapy, 21% were positive by RT-PCR and 13.7% and 8.4% by CellSearch for CTC≥2 and ≥5, respectively (Spearman, R=0.194, p=0.063). Overall concordance for CTC≥5 was 79.6% (Chi-Square, p=0.017). Agreement was also observed for CTC≥2, pre-and post-chemotherapy (Chi-Square, p=0.0001 and p=0.010). The concordance rates in the adjuvant and metastatic settings are shown in Table 1. Conclusions: A high concordance between the two methods was detected in metastatic but not in early disease. Patient follow-up will determine the clinical relevance of each individual assay or their combination in the assessment of patient prognosis. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-07-21.
Pioglitazone (pio), A Peroxisome Proliferator-activated Receptor (ppar)γ Agonist, Restores Efferocytosis Of Neutrophils In Chronic Granulomatous Disease (cgd) By Enhancing Oxidant Production And “Eat Me” Signaling
Authors: R. Fernandez-Boyanapall, S. Frasch, D.L. Bratton
Journal: Journal of Allergy and Clinical Immunology (2012)