tbuckley/cabot-search huggingface dataset:
The Majority of Expedited Investigational New Drug Safety Reports Are Uninformative
Authors: Jonathan P. Jarow, Sandra Casak, Meredith Chuk, Lori A. Ehrlich, Sean Khozin
Journal: Clinical Cancer Research (2016)

Sponsors of human drug and biologic products subject to an investigational new drug (IND) application are required to distribute expedited safety reports of serious and unexpected suspected adverse reactions to participating investigators and the FDA to assure the protection of human subjects participating in clinical trials. On September 29, 2010, the FDA issued a final rule amending its regulations governing expedited IND safety reporting requirements that revised the definitions used for reporting and clarified when to submit relevant and useful information to reduce the number of uninformative reports distributed by sponsors. From January 1, 2006, to December 31, 2014, the FDA's Office of Hematology and Oncology Products received an average of 17,686 expedited safety reports per year. An analysis of FDA submissions by commercial sponsors covering this time period suggested a slight increase in the number of expedited safety reports per IND per year after publication of the final rule. An audit of 160 randomly selected expedited safety reports submitted to the FDA's Office of Hematology and Oncology Products in 2015 revealed that only 22 (14%) were informative. The submission of uninformative expedited safety reports by commercial sponsors of INDs continues to be a significant problem that can compromise detection of valid safety signals. Clin Cancer Res; 22(9); 2111-3. ©2016 AACR.
1367 INCREASED GUT PERMEABILITY IN METABOLIC SYNDROME IS NOT ASSOCIATED WITH CHANGES IN BILE ACID PROFILE
Authors: B. Leber, N. Tripolt, S. Lemesch, A. Horvath, T. Stojakovic, G. Fauler, R. Stauber, P. Fickert, H. Sourji, V. Stadlbauer
Journal: Journal of Hepatology (2013)
Rendezvous biliary recanalization combining percutaneous and endoscopic techniques using a diathermic dilator for bile duct obstruction
Authors: Hiroshi Kawakami, Daisuke Abo, Kazumichi Kawakubo, Masaki Kuwatani, Yuki Yoshino, Yoshimasa Kubota, Yoko Abe, Shuhei Kawahata, Kimitoshi Kubo, Yusuke Sakuhara, Hiroki Shirato, Naoya Sakamoto
Journal: Endoscopy (2014)

Severe biliary injuries and strictures are intractable complications of hepatectomy. Endoscopic-radiologic biliary recanalization is a minimally invasive technique in patients undergoing hepatectomy. Here, we present a case of successful percutaneous transhepatic and endoscopic biliary rendezvous recanalization using a diathermic dilator for a benign severe postoperative biliary stricture.
Abstract 1892: Curcumin suppresses prostate cancer cells through modulation of β-catenin and protein kinase D1
Authors: Vasudha Sundram, Subhash C. Chauhan, Meena Jaggi
Journal: Cancer Research (2010)

Abstract OBJECTIVE: Prostate cancer is the most commonly diagnosed cancer in males in the US. One in every 6th male will be diagnosed with prostate cancer this year. Understanding the molecular basis of prostate cancer progression can serve as a tool for early stage diagnosis and development of novel treatment strategies for this disease. Inappropriate activation of β-catenin signaling is linked to a wide range of cancers, including prostate cancer, resulting in transcription of genes involved in cancer progression such as c-Myc, c-Jun and cyclin D1. However, strategies to regulate this specific signaling pathway are very limited or not well developed. Synthetic or natural products which regulate this signaling pathway can be developed as a novel therapeutic modality for prostate cancer treatment. Curcumin, the active ingredient of turmeric, has shown anti-cancer properties via modulation of a number of different molecular pathways. Herein, we have investigated a putative molecular mechanism involved in curcumin mediated suppression of prostate cancer cell growth and the effect of curcumin on prostate cancer cells growth and its effect on β-catenin transcription activity. MATERIALS AND METHODS: Cellular characteristics of the C4-2 prostate cancer cells were measured using anchorage independent growth, anchorage dependent growth, motility, and proliferation assays. β-catenin/T cell factor (TCF) transcription activity was measured by luciferase reporter assays using reporter constructs Topflash or Fopflash and pRL-TK (Renilla luciferase). The Luciferase activities were assayed using the Dual Glo reagent (dual reporter assay, Promega, Madison, WI). Subcellular localization of Protein Kinase D1 (PKD1) and β-catenin was determined by confocal microscopy. RESULTS: Our results demonstrate that curcumin effectively suppresses prostate cancer cell growth, proliferation and cellular motility. In the luciferase assays, curcumin treatment diminished β-catenin transcription activity in C4-2 prostate cancer cells. Moreover, curcumin treatment influences the translocation of β-catenin from the nucleus to the cell surface membrane. Interestingly, the suppression of β-catenin transcription activity was correlated with the modulation PKD1 expression/phosphorylation within 1-3 hrs post-curcumin treatment. CONCLUSION: These results suggest that curcumin treatment attenuates β-catenin transcription activity in prostate cancer cells via modulating the expression/activation of PKD1. These results suggest a novel molecular mechanism of curcumin related suppression of prostate cancer cell growth. 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 1892.
Are There More Tumor Necrosis Factors?
Authors: M A Palladino
Journal: JNCI Journal of the National Cancer Institute (1989)

Journal Article Are There More Tumor Necrosis Factors? Get access Michael A. Palladino Michael A. Palladino Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 81, Issue 7, 5 April 1989, Pages 474–475, https://doi.org/10.1093/jnci/81.7.474 Published: 05 April 1989 Article history Received: 28 February 1989 Accepted: 01 March 1989 Published: 05 April 1989
THU0102 EULAR-DAS28 versus RAPID3 for treatment monitoring in patients with rheumatoid arthritis treated with rituximab
Authors: C.M. Ancuta, C. Belibou, E. Ancuta, S. Miu, R. Chirieac
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> treat-to-target and tight control strategies are actually the two main paradigms in the treatment of rheumatoid arthritis (RA), aiming to improve patients outcome by achieving either remission or minimal disease activity status. There is actually no consensus regarding the right assessment tools for monitoring the magnitude of improvement and the absolute reached level in routine clinical practice. <h3>Objectives</h3> to compare EULAR-DAS28 with RAPID3 (a patient-reported outcome based on pain, patient global assessment of disease activity, and multidimensional HAQ)response criteria in patients with moderate to severe active RA treated with rituximab (RTX). <h3>Methods</h3> prospective observational study on 72 moderate to severe active RA (DAS28&gt;3.2) receiving one cycle of RTX (two infusions of 1000 mg at two weeks interval). Response to treatment was appreciated at six months by: (i) EULAR-DAS28 response criteria, classified as EULAR good (decrease with 1.2 units), moderate (decrease of 0.6–1.2 units) or non-responder (decrease ≤0.6 units); and (ii) RAPID3 response categories defined as good (decrease with 3.6 units), moderate (decrease of 1.8–3.6 units) and poor (decrease ≤1.8 units). Statistical analysis was done in SPSS.16 (weighted kappa statistics, p&lt;0.05. <h3>Results</h3> up to 85% of RA has been classified as good and moderate responders based on RAPID3, while about 75% have been responders according to EULAR-DAS28; moreover, nearly 45% of the RAPID3 good responders have also been categorized as moderate EULAR-DAS28 responders. Statistical significant moderate agreement between the EULAR-DAS28 response criteria and RAPID3 has been demonstrated (p&lt;0.05). <h3>Conclusions</h3> Patient-centered tools such as RAPID3 allow more easily and quickly to quantify disease activity levels and patient responses to therapy, providing a more complex insight into the patient's perception of disease status. <h3>Disclosure of Interest</h3> None Declared
The Utility of the Blood Pepsin Assay in Clinical Medicine
Authors: Howard M. Spiro, Anna E. Ryan, Chester M. Jones
Journal: New England Journal of Medicine (1955)

CONVENTIONAL study of gastric secretion is limited by several factors, including the effect of the tube in the stomach. Such an unpleasant procedure may stimulate or may inhibit gastric secretion; indeed, it may be so distasteful as to preclude passage of the tube. Therefore, re-emphasis on the fact that peptic activity in the urine reflects gastric secretory activity1 stimulated much research into this more physiologic approach. Still, even urine collections were uncertain, and it was suggested that changes in water and electrolyte balance and in renal clearance might affect uropepsin excretion.Mirsky et al.,2 in 1952, described a method of . . .
M41 Recurrent Tuberculosis And Its Risk Factors In The Uk's Largest Tb Centre
Authors: K. Avery, R. Ghani, J. Buckley, L. John, R. Davidson
Journal: Thorax (2014)

<h3>Objective</h3> To describe tuberculosis (TB) relapse/recurrence in patients treated at the UK’s largest TB centre and identify characteristic which predicted recurrence. <h3>Design</h3> Retrospective observational cohort study. <h3>Methods</h3> All patients treated at our centre between 1st Jan 2002–31st Dec 2013 were identified from the local TB register. We excluded patients who died due to TB or whose outcome was unknown. Details of patients with more than one notification episode of TB were obtained from patient records. <h3>Results</h3> In total, 3534 patients were treated for TB during the 12-yr period. After exclusions, 3515 patients were included in the study. Of these, 42 patients had two notifications of TB; none were treated more than twice. Of these 42, we considered 14 to be true relapses/recurrences. 28 patients were considered on review not to have had a true relapse/recurrence: of these, 11 had their first treatment episode at a different centre; 9 were re-starts of treatment because of non-adherence during the first TB episode; 2 had intracranial tuberculomas diagnosed within 12 months of initial episode; 6 were errors in notification. Of 14 patients considered to be true relapses/recurrence, 6 were microbiologically confirmed on relapse/recurrence and a further 8 were re-treated on clinical grounds. None exhibited drug resistance and 2 were HIV positive. The 14 true relapse/recurrence patients had mean age = 42 yrs (range 18–83 yrs) and 6 were males. The sites of relapse were: pulmonary in 6 cases, 3 patients had intracranial tuberculomas, 2 patients had bony TB, 3 patients had TB lymphadenitis. The mean time to relapse/recurrence was 41 months (range 2–96 mo). All 14 patients responded favourably to re-treatment. The true relapse rate of TB treated at the centre was 0.4%. The age, gender and ethnicity of the relapse cases were similar to the overall TB case-mix. <h3>Conclusions</h3> Our true relapse/recurrence rate of TB is very low, and had no obvious risk factors. We cannot determine retrospectively whether these were recurrence or reinfection, but strain typing (DNA fingerprinting) could differentiate these.
Abstract 5238: Impaired angiogenesis as a hallmark of prolonged tumor dormancy in a mouse model of human glioblastoma
Authors: Shiran Ferber, Ehud Segal, Nava Almog, Ronit Satchi-Fainaro
Journal: Cancer Research (2012)

Abstract Small sized, microscopic, non-invasive, avascular and therefore asymptomatic tumors can remain in their dormant stage for considerable period of time depending on numerous processes. One crucial mechanism underlying the transformation from a dormant phenotype to a fast-growing phenotype is the ability of the tumor cells to induce angiogenesis, a phenomenon termed as the “angiogenic switch”. Suspected dormant tumor-generating clone, derived from aggressive tumor-forming U-87 MG human glioblastoma cell line, was isolated using single-cell clone and identified by gene expression signature of dormant tumors (Almog et al., Cancer Research 2009). In order to evaluate the phenotypic differences between cell lines that generate dormant avascular tumors or fast-growing angiogenic tumors, we established a pair of mCherry-labeled human glioblastoma cell lines, U-87-D (Dormant) derived from the parental U-87-F (Fast-growing). While the two cell lines share similar growth rate in vitro, we found profound differences in tumor growth pattern when injected into mice. U-87-F established palpable and vascularized tumors only few days following inoculation, whereas U-87-D-generated tumors remained at a small size for more than 100 days. We further characterized both cell lines using migration, invasion and capillary-like tube formation assays in vitro. Major differences in invasiveness via a monolayer of human umbilical vein endothelial cells (HUVEC) were found. Furthermore, considerably increased number of tube-like structures formed from HUVEC were observed in the presence of U-87-F conditioned media (CM), compared with those formed in the presence of U-87-D CM. Similarly, HUVEC migration towards U-87-F CM was significantly higher compared with that towards U-87-D CM. Next, we utilized non-invasive intravital imaging to evaluate tumor progression, and non-invasive endo-microscopy imaging, as well as microbubbles contrast-enhanced ultrasound imaging, to track the blood flow within the tumor and blood vessels morphology at the tumor microenvironment. We concluded that the dormant and fast-growing tumors displayed distinct differences in their angiogenic potential leading to highly diverse tumor progression profiles when injected into mice. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5238. doi:1538-7445.AM2012-5238
Abstract 468: Phenotyping TILs in situ: Automated enumeration of intra- and extra-follicular Foxp3+ regulatory T cells in follicular lymphoma.
Authors: James Mansfield, Lilli Nelson, Chris van der Loos, Richard Byers
Journal: Cancer Research (2013)

Abstract Background. In many cancers, tumor-infiltrating lymphocytes (TILs) indicate levels of tumor immunogenicity and are a strong predictor of survival. In particular, increased levels of regulatory T cells (Tregs) are associated with poorer prognosis in some cancers. An understanding of the phenotype and spatial distribution of TILs in situ within tumor regions would be advantageous. However, visual TIL assessment cannot easily determine the type of lymphocyte in situ and multimarker quantitation is difficult with standard methods. Here we present a multi-marker, computer-aided event-counting method for determining the phenotypes of lymphocytes in follicular lymphoma sections using a multispectral imaging (MSI) and automated tissue segmentation and counting approach. Design. A single section of a tissue microarray containing 70 follicular lymphoma cores from [42 male, 28 female, 17 alive and 53 dead at the end of followup, survival range 2-171 months (median 55 months)] was stained for CD3, Foxp3 and hematoxylin. Each core was imaged using MSI and the individual staining of each marker separated from each other using spectral unmixing. The images were analyzed using software which had been trained to recognize the follicular areas based on the tissue morphology. Then the Foxp3 status of each CD3+ TIL was then determined and the number of each Treg (Foxp3+ T cell) counted for both the intra- and extra-follicular tissue compartments. Results. Results indicate that machine-learning software can be trained to accurately recognize follicular and non-follicular regions within each core. MSI enabled the accurate quantitation of two immunostains in the sample without crosstalk. The number of Tregs were determined for each core and ranged from 0 to 453 per core (median 58, stddev 97.5). Conclusion. Understanding the number and location (intra- and extra-follicular) of Tregs is an assay with potentially important clinical prognostic implications. Thus study shows that an automated method for counting Tregs can be developed for follicular lymphoma. This multimarker phenotyping and counting approach shows the potential for broad applicability in the enumeration of a wide range of specifically phenotyped TILs in situ in many solid tumors. Citation Format: James Mansfield, Lilli Nelson, Chris van der Loos, Richard Byers. Phenotyping TILs in situ: Automated enumeration of intra- and extra-follicular Foxp3+ regulatory T cells in follicular lymphoma. [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 468. doi:10.1158/1538-7445.AM2013-468
ACUTE IMPROVEMENT OF PULMONARY CONGESTION DOES NOT IMPACT CHEYNE-STOKES RESPIRATION SEVERITY IN CHRONIC HEART FAILURE: A RANDOMIZED, CONTROLLED TRIAL
Authors: Thomas Bitter, Heidi Schmalgemeier, Henrik Fox, Andrea Zwenke, Dieter Horstkotte, Olaf Oldenburg
Journal: Journal of the American College of Cardiology (2015)
Wnt pathway in atypical teratoid rhabdoid tumors
Authors: Madhavi Chakravadhanula, Chris N. Hampton, Parth Chodavadia, Victor Ozols, Li Zhou, Daniel Catchpoole, Jingying Xu, Anat Erdreich-Epstein, Ratan D. Bhardwaj
Journal: Neuro-Oncology (2014)

Atypical teratoid rhabdoid tumor (ATRT) is an aggressive pediatric brain tumor with limited therapeutic options. The hypothesis for this study was that the Wnt pathway triggered by the Wnt5B ligand plays an important role in ATRT biology. To address this hypothesis, the role of WNT5B and other Wnt pathway genes was analyzed in ATRT tissues and ATRT primary cell lines. Transcriptome-sequencing analyses were performed using nanoString platforms, immunohistochemistry, Western blotting, quantitative reverse transcriptase PCR, immunoprecipitation, short interference RNA studies, cell viability studies, and drug dose response (DDR) assays. Our transcriptome-sequencing results of Wnt pathway genes from ATRT tissues and cell lines indicated that the WNT5B gene is significantly upregulated in ATRT samples compared with nontumor brain samples. These results also indicated a differential expression of both canonical and noncanonical Wnt genes. Imunoprecipitation studies indicated that Wnt5B binds to Frizzled1 and Ryk receptors. Inhibition of WNT5B by short interference RNA decreased the expression of FRIZZLED1 and RYK. Cell viability studies a indicated significant decrease in cell viability by inhibiting Frizzled1 receptor. DDR assays showed promising results with some inhibitors. These promising therapeutic options will be studied further before starting a translational clinical trial. The success of these options will improve care for these patients.
Abstract 4749: Genetic signature of malignant glioma is associated with responsiveness to autologous tumor lysate-pulsed dendritic cell vaccination + TLR agonists
Authors: Robert M. Prins, Horacio Soto, Vera Konkankit, William H. Yong, Stanley F. Nelson, Linda M. Liau
Journal: Cancer Research (2010)

Abstract Purpose: We previously reported that the toll-like receptor (TLR)-7 agonist, imiquimod, could enhance dendritic cell activation and migration, as well as stimulate T cell-mediated anti-tumor immune responses in a murine glioma model. To translate these findings, a Phase I clinical trial was initiated to evaluate this strategy for its feasibility, safety, and induction of immune responses in patients with malignant glioma. Herein, we report the results of this phase I, dose escalation clinical trial using autologous tumor lysate-pulsed dendritic cell (DC) vaccination, supplemented with the toll-like receptor agonists, imiquimod or poly ICLC, for patients with malignant glioma. Patients and Methods: Twenty-two glioblastoma patients (15 newly diagnosed, 7 recurrent) were enrolled into a multi-cohort dose-escalation study and treated with 1, 5, or 10 million autologous DC pulsed with tumor lysate. Three biweekly intradermal vaccinations were initially administered. Subsequently, patients received booster vaccinations together with imiquimod or poly ICLC every three months until tumor progression or lysate was depleted. Patients were monitored for adverse events, survival, and immune responses. For patients with available pre-treatment tumor and/or PBMC, microarray-based hierarchical clustering, lymphocyte immunohistochemistry, FACS and cytokine bead arrays were performed for monitoring purposes. Results: DC vaccinations were not associated with any evidence of dose-limiting toxicity or serious adverse effects. The median survival was 35 months for newly diagnosed patients and 11 months for recurrent patients, but still increasing as several patients are still alive at this point. Typical glioblastoma gene expression signatures, previously characterized by our group, were found. Contrary to our previous reports, however, patients with proliferative (Pro) or mesenchymal (Mes) signatures exhibited prolonged survival, while patients with pro-neural (PN) signatures did not. Pre-treatment Pro, Mes or Pro/Mes tumor sections had increased CD3 and CD8 positive cells within the tumor compared with PN tumor sections. Conclusions: Pro, Mes or Pro/Mes gene expression signatures may identify patients with pre-existing immunity and who may benefit from immune-based vaccination studies. However, prospective studies will need to be performed to establish the validity of these findings. 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 4749.