tbuckley/cabot-search huggingface dataset:
Specific inhibition of hepatitis C viral gene expression by antisense phosphorothioate oligodeoxynucleotides*1
Authors: M ALT
Journal: Hepatology (1995)

The inhibitory effect of antisense phosphorothioate oligodeoxynucleotides (S-ODN) on hepatitis C viral gene expression was analyzed in an in vitro test system and in cell culture. S-ODN were directed against different stem loop structures in the 5′ noncoding region (NCR) of the hepatitis C virus (HCV) RNA and against a nucleotide stretch, including the start codon of the polyprotein precursor. The inhibitory effect of these S-ODN was quantified employing a viral RNA consisting of the first 407 nucleotides of a HCV type lb genome fused to the coding sequence of the firefly luciferase gene. For in vitro assays this RNA was generated by in vitro transcription and used as a template in a rabbit reticulocyte lysate in vitro translation system. The production of active luciferase in the absence or presence of S-ODN was monitored using an enzymatic assay. The best results were obtained with S-ODN 4 directed against nucleotides 326 to 348, comprising the start AUG of the polyprotein coding sequence. With this oligonucleotide, a specific and dose-dependent effect was observed with a maximal inhibition of 96 ± 1% at a S-ODN concentration of 4.14 μmol/L. For cell culture experiments, the hepatoblastoma cell line HepG2 was transfected with a plasmid expressing the HCV-luciferase fusion RNA. In this assay system S-ODN 2, complementary to nucleotides 264 to 282 of the HCV RNA, and S-ODN 4 were most efficient and reduced the viral translation by 96 ± 0.4% and 94 ± 0.7%, respectively, at a concentration of 0.3 μmol/L. The inhibition was specific (1) because the expression of the HCV-luciferase fusion RNA was not significantly impaired by the control S-ODN and (2) because the expression of an unrelated messenger RNA was not or only slightly downregulated. These data suggest that HCV gene expression can be inhibited effectively by antisense S-ODN. Therefore, this approach represents a promising perspective for the treatment of hepatitis C.
Breast Cancer Prevention: Hold the Hormones, Please
Authors: Kara Smigel
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article Breast Cancer Prevention: Hold the Hormones, Please Get access Kara Smigel Kara Smigel Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 17, 4 September 1991, Pages 1211–1213, https://doi.org/10.1093/jnci/83.17.1211 Published: 04 September 1991
ET-15 * APPLICATION OF A COMBINATORIAL NATURAL PRODUCT THERAPY FOR THE TREATMENT OF HIGH-GRADE GLIOMAS
Authors: L. Deleyrolle, R. Martuscello, B. Griffith, H. Futch, C. Skinner, J. McGuiness, C. Louviere, B. Reynolds
Journal: Neuro-Oncology (2014)

Application of toxic compounds used at maximum tolerated dose until resistance develops is the most commonly experienced outcome in cancer therapy. Based on successful concepts borrowed from the field of ecology to manage pest populations, we developed a therapeutic strategy relying on the use of multiple independent and non-toxic stressors that enable efficient horizontal and vertical targeting of the tumor. Our treatment (CA.001) uses a combination of two distinct approaches. The first aspect of our approach involves the simultaneous application of three natural products (curcumin, epigallocatechin-3-gallate and sulforaphane) that have previously demonstrated anticancer properties and have a documented safety profile. Each individual natural product (NP) is able to inhibit in vitro the expansion of glioma cancer stem cells with the combination of all three compounds producing a synergistic effect. The NP combination also demonstrated greater ability to decrease tumor progression and increase survival in a clinically relevant orthotopic xenograft model of glioma. The second component of our treatment is a metabolic targeting through dietary alteration limiting the intake of carbohydrates, thereby reducing glucose metabolism, which represents the main source of energy production for cancer cells (for details see poster Martuscello et.al.). Animals intracranially xenografted with glioma cells show greater survival when treated with the combination of the metabolic treatment coupled with the NPs. Notably, CA.001 works synergistically with the conventional chemotherapy temozolomide (TMZ) and has proven to be an effective therapeutic against TMZ-resistant glioma cells. Interestingly, CA.001 is able to sensitize TMZ-resistant cells to TMZ. Additionally, we demonstrated the absence of toxicity related to CA.001 treatment based on organ health- evaluated by clinical chemistry measuring blood enzyme levels and by organ weight comparison, as well as hematology- using complete blood count. Collectively, these data suggest CA.001 as a viable non-toxic and affordable antineoplastic treatment to treat high-grade glioma.
Prevalence and Characteristics of Physicians Prone to Malpractice Claims
Authors: David M. Studdert, Marie M. Bismark, Michelle M. Mello, Harnam Singh, Matthew J. Spittal
Journal: New England Journal of Medicine (2016)

The distribution of malpractice claims among physicians is not well understood. If claim-prone physicians account for a substantial share of all claims, the ability to reliably identify them at an early stage could guide efforts to improve care.Using data from the National Practitioner Data Bank, we analyzed 66,426 claims paid against 54,099 physicians from 2005 through 2014. We calculated concentrations of claims among physicians. We used multivariable recurrent-event survival analysis to identify characteristics of physicians at high risk for recurrent claims and to quantify risk levels over time.Approximately 1% of all physicians accounted for 32% of paid claims. Among physicians with paid claims, 84% incurred only one during the study period (accounting for 68% of all paid claims), 16% had at least two paid claims (accounting for 32% of the claims), and 4% had at least three paid claims (accounting for 12% of the claims). In adjusted analyses, the risk of recurrence increased with the number of previous paid claims. For example, as compared with physicians who had one previous paid claim, the 2160 physicians who had three paid claims had three times the risk of incurring another (hazard ratio, 3.11; 95% confidence interval [CI], 2.84 to 3.41); this corresponded in absolute terms to a 24% chance (95% CI, 22 to 26) of another paid claim within 2 years. Risks of recurrence also varied widely according to specialty--for example, the risk among neurosurgeons was four times as great as the risk among psychiatrists.Over a recent 10-year period, a small number of physicians with distinctive characteristics accounted for a disproportionately large number of paid malpractice claims.
Abstract LB-196: Anti-DLL4 reduces tumor growth and tumorigenicity in B-RAF V600E melanomas including those with acquired resistance to B-RAF inhibitors
Authors: Lucia Beviglia, Pete Yeung, Marcus Fischer, Wang-Ching Yen, Austin Gurney, John Lewicki, Ann Kapoun, Timothy Hoey
Journal: Cancer Research (2012)

Abstract Melanoma is frequently driven by oncogenic mutation in the B-RAF gene (V600E) and this mutation is found in approximately 60% of patients. These patients are highly sensitive to kinase inhibitors targeting B-RAF. However, recent clinical experience has shown that after an initial response, a high percentage of patients develop resistance to B-RAF inhibitors through various mechanisms. In our studies, we evaluated whether inhibition of DLL4-Notch signaling might be effective in B-RAF mutant melanoma. We utilized two patient-derived melanoma xenografts containing the B-RAFV600E mutation, OMP-M2 and OMP-M8. The OMP-M8 xenograft was derived from a patient who was treated with the B-RAF inhibitor Vemurafenib (PLX-4032) and showed an early response to treatment, but later became resistant. We performed combination efficacy experiments with the B-RAF inhibitor PLX-4720 (doses 20-80 mg/kg, oral gavage, qdx5) and anti-DLL4 antibodies (30 mg/kg, IP once a week), and found that PLX-4720 combined with anti-DLL4 treatment caused a significant inhibition of tumor growth in OMP-M2 tumors. In serial transplant limiting dilution assay (LDA) studies with the OMP-M2 model, PLX-4720 treatment induced a significant enrichment of tumor initiating cells. In contrast, anti-DLL4 reduced the frequency of tumor initiating cells compared to controls, as a single agent and in combination with PLX-4720. We also found that the OMP-M8 tumor xenografted in mice retained the lack of response to the B-RAF kinase inhibitor, showing that the xenografts responded to treatment similarly as the patient in the clinic. Interestingly, the B-RAF inhibitor resistant tumor OMP-M8 was sensitive to anti-DLL4, which inhibited the growth of the primary tumor and significantly reduced the frequency of tumor initiating cells as a single agent and in combination with a chemotherapeutic agent. These findings suggest that DLL4-Notch inhibition can be effective in B-RAF V600E mutant melanoma including patients with acquired resistance to B-RAF kinase inhibitors. 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 LB-196. doi:1538-7445.AM2012-LB-196
Abstract P2-05-05: Circulating HER2 extracellular domain (ECD) predicts a poor prognosis for metastatic breast cancer patients
Authors: X-j Wang, X-Y Shao, X-H Xu, Z-H Chen, S Wang, J-F Cai, J Huang, P Huang, C-J Lou, Z-Q Ling, MX Han
Journal: Cancer Research (2012)

Abstract Background: Amplification or overexpression of HER2 has been shown to play an important role in approximately 30% of breast cancers and is strongly associated with increased recurrence and a worse prognosis. The HER2 extracellular domain (ECD) may be cleaved and shed from the surface of breast cancer cells and serum HER2 ECD levels can be detected by enzyme-linked immunosorbent assay (ELISA). In this study, we explored the relationship between circulating HER2 ECD and tissue HER2 status, then we also examined its predictive value in a cohort of metastatic breast cancer patients. Methods: Two hundred and seven metastatic breast cancer patients from March 2009 to July 2011 were involved in this prospective study at Zhejiang Cancer Hospital. The patients were identified histopathologically as having breast cancer by pathologists and staged mainly based on the pathology, the clinical manifestation, and the imaging findings of CT and MRI according to the classification system of the International Union Against Cancer. Serum HER2 ECD levels were measured by ELISA. Tissue HER2 was determined by IHC and FISH in tumor samples, respectively. Results: The level of serum HER2 ECD was at least more than 15 ng/ml in 31.4% (65/207) metastatic breast cancer patients, 39.1%(43/110) in HER2-positive patients and 23.4%(22/94) in HER2-negative cases, respectively, P = 0.017. We also found that high serum HER2 ECD levels (≥15 ng/ml) were significantly associated with elevated serum CEA (52.1% v 21.5%, OR 3.978, 95%CI 2.138–7.401, P = 0.000), CA125 (48.5% v 23.5%, OR 3.064, 95%CI 1.650–5.691, P = 0.000), CA153 (53.2% v 17.1%, OR 5.48, 95%CI 2.897–10.366, P = 0.000), LDH (53.3% v 23.1%, OR 3.798, 95%CI 2.011–7.173, P = 0.000) and AKP (51.2% v 26.5%, OR 2.911, 95%CI 1.442–5.879, P = 0.002), respectively. For the effect of HER2 ECD on the site of relapse, still there were statistically significant correlation between increased serum HER2 ECD levels and liver involvement (42.7% v 24.0%, OR 2.358, 95%CI 1.294–4.297, P = 0.005), brain metastasis (50.0% v 26.7%, OR 2.744, 95%CI 1.397–5.391, P = 0.003) and visceral involved (37.9% v 14.8%, OR 3.511, 95%CI 1.548–7.961, P = 0.002), respectively. While serum HER2 ECD levels were not related to age, BMI, tumor size, lymph node involvement and hormone receptors status, respectively (P&amp;gt;0.05). Conclusions: Monitoring the circulating levels of the HER2 ECD in patients with metastatic breast cancer provides a real-time assessment of tumor burden and indicates poor prognosis, and may provide important information for reassessment of HER2 in HER2-negative metastatic breast cancer. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-05-05.
Vaccine effectiveness in preventing laboratory-confirmed influenza in Navarre, Spain: 2013/14 mid-season analysis
Authors: J Castilla, I Martínez-Baz, A Navascués, M Fernandez-Alonso, G Reina, M Guevara, J Chamorro, M T Ortega, E Albéniz, F Pozo, C Ezpeleta, Collective Primary Health Care Sentinel Network, Collective Network for Influenza Surveillance in Hospitals of Navarre
Journal: Eurosurveillance (2014)

We estimate mid-2013/14 season vaccine effectiveness (VE) of the influenza trivalent vaccine in Navarre, Spain. Influenza-like illness cases attended in hospital (n=431) and primary healthcare (n=344) were included. The overall adjusted VE in preventing laboratory-confirmed influenza was 24% (95% CI: ?14 to 50). The VE was 40% (95% CI: ?12 to 68) against influenza A(H1)pdm09 and 13% (95% CI: ?36 to 45) against influenza A(H3). These results suggest a moderate preventive effect against influenza A(H1)pdm09 and low protection against influenza A(H3).
Rituximab monotherapy for relapsed or refractory primary central nervous system lymphoma
Authors: T. T. Batchelor, G. J. Lesser, S. A. Grossman
Journal: Journal of Clinical Oncology (2008)

2043 Background: Rituximab, a chimeric monoclonal antibody against the CD20 antigen, improves survival when combined with CHOP therapy in patients with systemic diffuse large B-cell lymphoma (DLBCL). Approximately 90% of primary central nervous system lymphomas (PCNSL) are DLBCL and rituximab is now part of combination therapy in some regimens for PCNSL with only anecdotal evidence of efficacy in this patient population. Methods: Adult patients with relapsed or refractory CD20+ PCNSL are being enrolled in a National Cancer Institute-sponsored multicenter phase II trial of rituximab monotherapy in the New Approaches to Brain Tumor Therapy (NABTT) consortium. All patients failed prior methotrexate-based therapy. Rituximab is administered at a dose 375 mg/m2 in weekly intravenous infusions for a maximum of 8 treatments. The primary objectives are to determine the radiographic response proportion, progression-free and overall survival. The study design is a two-stage phase II trial with 15 patients in stage I and 10 additional patients in stage II. Results: Nine patients have been enrolled at the time of this submission. There have been 3 (1 CR, 2 PR) objective radiographic responses in the first 9 patients enrolled. Eight patients have progressed from 3–228 days after treatment and 4 patients have died. The rituximab responses lasted 174 days, 228 days and 324+ days. Four patients have experienced CTC grade 3 or 4 toxicity potentially related to rituximab with adverse events consisting of allergic reaction, fatigue, anxiety and pain. Conclusions: Rituximab monotherapy in patients with relapsed or refractory CD20+ PCNSL results in radiographic regression of tumor in a subset of patients and warrants further study in combination with other chemotherapeutic agents. Enrollment and follow-up are ongoing. No significant financial relationships to disclose.
Abstract 1127: Lack of MAPK activation in significant number of uveal melanomas with somatic mutation in <i>GNAQ</i> and <i>GNA11</i>
Authors: Mohamed H. Abdel-Rahman, Getachew Boru, Colleen M. Cebulla, Benjamin Christopher, James B. Massengill, Davidorf H. Frederick
Journal: Cancer Research (2011)

Abstract Purpose: The aims of this study were to investigate the correlation between MAPK activation and somatic mutation in GNAQ and GNA11 genes in uveal melanoma (UM) and to investigate the potential utility of MEK inhibition as a target for therapy of UM in tumors with GNAQ and GNA11 mutations. Methods: Sequencing and restriction fragment length polymorphism (RFLP) were utilized for detection of activating mutations in codon 209 of the GNAQ and GNA11 genes in 44 primary UMs. The expression of phospho p44/42 MAPK (pERK1/2) was assessed by immunohistochemistry in 44 UMs. In addition, the expression of pERK1/2 and pMEK 1/2 were studied using Western blot analysis in 17 primary UMs (14 with GNAQ or GNA11 mutations) and five UM cell lines (C918, 92.1, OCM3, MEL202, MEL270). Three of the UM cell lines (92.1, MEL202 and MEL270) have GNAQ codon 209 mutations. The effect of three different selective MEK inhibitors (U126, PD98059 and PD184352) on UM cell proliferation and apoptosis were studied. Results: The majority (30/44, 68.2%) of the primary UM tumors showed somatic mutation in codon 209 of either the GNAQ or the GNA11 genes. With the exception of one tumor, the mutations in either gene were mutually exclusive. Of the 30 UM primary tumors with GNAQ and/or GNA11 mutation, pERK1/2 expression was absent in 26.7%, weak in 33.3%, moderate in 23.3%, and high in only 16.7%. Western blot showed no pMEK1/2 expression in 6/14 (42.9%) of UM with either GNAQ or GNA11 mutations. Two of the UM cell lines with GNAQ mutation showed weak pERK1/2 expression. In addition one showed no pMEK1/2 expression while the other one showed very weak pMEK1/2 expression. Selective MEK inhibitors slowed UM cell proliferation but didn't induce significant apoptosis in UM cell lines regardless of GNAQ status. Conclusions: Our results indicate that a significant number of UM with somatic mutations in GNAQ or GNA11 showed no MAPK pathway activation. In UM, MEK inhibition is mostly cytostatic suggesting that selective MEK inhibitors alone may not be sufficient to control UM. 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 1127. doi:10.1158/1538-7445.AM2011-1127
F-18 FDG Pericardial Uptake Secondary to Recent Cardiac Surgery
Authors: N. PANDIT, H. W. YEUNG
Journal: Clinical Nuclear Medicine (2001)

From the Division of Nuclear Medicine, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York Received for publication November 27, 2001. Accepted April 2, 2001. Reprint requests: H. W. Yeung, Division of Nuclear Medicine, Department of Radiology, Memorial Sloan Kettering Cancer Center, 1255 York Avenue, New York, New York 10021.
WITHDRAWN: Human organic anion transporter 4-mediated transport of olmesartan in placenta
Authors: Saki Noguchi, Tomohiro Nishimura, Ayasa Fujibayashi, Tetsuo Maruyama, Masatoshi Tomi, Emi Nakashima
Journal: Asian Journal of Pharmaceutical Sciences (2015)

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.
Some Unusual Aspects of Cancer of the Breast
Authors: Ernest M. Daland
Journal: New England Journal of Medicine (1945)

CANCER of the breast in its early stages usually gives few if any symptoms, and ordinarily it is quite by accident that the patient notices a lump. If she waits until pain is a factor before consulting a physician, the disease is usually advanced. Unfortunately, she does not always seek medical advice at once and there is often a delay of several months.The extent of the disease at the time of examination and treatment really determines the outcome in each case. It is known that there are varying degrees of malignancy, and that some cancers grow and metastasize more . . .
NI-69 * UTILITY OF 18F-FDG PET/MR IN DIFFERENTIATION OF RECURRENT HIGH-GRADE GLIOMA FROM DELAYED RADIATION TISSUE INJURY: COMPARISON OF PET/CT TO PET/MR
Authors: A. Sher, J. Montagnese, L. Rogers, S. Abboud, L. Wolansky
Journal: Neuro-Oncology (2014)

PURPOSE: In a prior study of malignant brain tumors, we found 18F-FDG PET/MR to be superior to 18F-FDG PET/CT for distinguishing between progressive disease (PD) and radiation change (RC) (unpublished data). The purpose of this study is to compare the diagnostic accuracy of 18F-FDG PET/CT vs. 18F-FDG PET/MR in differentiating PD from RC in a subpopulation of malignant gliomas. METHODS: We evaluated 10 patients with high-grade gliomas whom had previously undergone chemoradiation therapy and developed MR evidence of PD per RANO criteria. All patients underwent 18F-FDG PET/CT, 18F-FDG PET/MR (MR attenuation correction, PET/MRAC), and conventional diagnostic MR (PET/MRD). pMR was also performed. Separate consensus blinded readings by two fellowship-trained radiologists (1 neuroradiology; 1 nuclear) were performed to assess the diagnostic efficacy of PET/CT, PET/MRAC, and PET/MRD. A qualitative subjective rating was given to each lesion (1 = definite RC; 2 = probable RC; 3 = equivocal; 4 = probable PD; 5 = definite PD). Sensitivity, specificity, and accuracy were determined for the three interpretation sessions after binary reclassification, with a rating of 1-3 defined as RC and 4-5 defined as PD. Wilcoxon-rank test was used for rating comparison between the three interpretations. RESULTS: PET/CT yielded sensitivity, specificity, and accuracy of 0.78, 1.00, and 0.80, respectively. Both PET/MRAC and PET/MRD demonstrated a sensitivity, specificity, and accuracy of 1.00, 1.00, and 1.00. There was no statistically significant difference in interpretation between PET/CT, PET/MRAC or PET/MRD. CONCLUSION: In this small series, 18F-FDG PET/MR utilizing either diagnostic or attenuation-only MR sequences had higher sensitivity and overall accuracy in delineating progressive disease from radiation change in glioma patients compared to 18F-FDG PET/CT. However, the difference was not statistically significant. A larger series is in progress to increase the power of the study in interpretation between 18F-FDG PET/MR and 18F-FDG PET/CT.
Recent and Past Use of Conjugated Estrogens in Relation to Adenocarcinoma of the Endometrium
Authors: Samuel Shapiro, David W. Kaufman, Dennis Slone, Lynn Rosenberg, Olli S. Miettinen, Paul D. Stolley, Neil B. Rosenshein, Watson G Watring, Thomas Leavitt, Robert C. Knapp
Journal: New England Journal of Medicine (1980)

It has been suggested that the reported association between estrogen use and endometrial cancer may have been biased because estrogens provoke uterine bleeding in women with otherwise asymptomatic disease. To evaluate this hypothesis we compared 149 patients with endometrial cancer and 402 control subjects with other conditions with reference to the time when they had last used conjugated estrogens. In women who had last used conjugated estrogens two or more years previously and who had taken them for at least five years, the rate-ratio estimate was 3.3 (95 per cent confidence interval, 1.4 to 8.0) relative to women who had never used them. Uterine bleeding, and hence the diagnosis of otherwise asymptomatic cancer, cannot be attributed to estrogen use that ceased in the distant past. Our results suggest that such use has a residual effect on the risk of endometrial cancer; this effect is not accounted for by biased selection of cases according to estrogen use.
GASTROSTOMÍA ENDOSCÓPICA PERCUTÁNEA BAJO SEDACIÓN CON PROPOFOL CONTROLADA POR ENDOSCOPISTA
Authors: LR Gotuzzo, G Payeras, MA Huertas, R Barranco, A Calvache, R Briz
Journal: Endoscopy (2011)

Introducción: La gastrostomía endoscópica percutánea (PEG) es una técnica endoscópica que suele realizarse en pacientes de riesgo anestésico elevado. El propofol es un agente hipnótico usado cada vez con más frecuencia en procedimientos endoscópicos básicos. Existen pocos trabajos que valoren la seguridad del propofol en procedimientos de endoscopia avanzada cuando éste es utilizado por el endoscopista.