tbuckley/cabot-search huggingface dataset:
Comparison of a Second-Generation Combination Chemotherapeutic Regimen (m-BACOD) with a Standard Regimen (CHOP) for Advanced Diffuse Non-Hodgkin's Lymphoma
Authors: Leo I. Gordon, David Harrington, Janet Andersen, Joseph Colgan, John Glick, Richard Neiman, Risa Mann, Gene D. Resnick, Maurice Barcos, Arlan Gottlieb, Michael O'Connell
Journal: New England Journal of Medicine (1992)

In 1984, the Eastern Cooperative Oncology Group began a randomized controlled clinical trial of patients with advanced (stage III or IV) diffuse mixed or diffuse large-cell lymphoma to determine whether complete-remission rates, survival, and toxicity differed when patients were treated with a chemotherapeutic regimen containing cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), as compared with a regimen containing bleomycin, doxorubicin, cyclophosphamide, vincristine, dexamethasone, methotrexate, and leucovorin (m-BACOD).
Abstract 388: Epithelial to mesenchymal transition is associated with acquired resistance to sunitinib in patients with renal cell carcinoma: evidence from a xenograft study
Authors: Hans J. Hammers, Henk Verheul, Brenda Salumbides, Rajni Sharma, Janneke Jaspers, Michelle Rudek, George Netto, Roberto Pili
Journal: Cancer Research (2010)

Abstract Purpose: Tyrosine kinase inhibitors (TKIs) targeting angiogenesis via inhibition of the vascular endothelial growth factor (VEGF) pathway have changed the medical management of metastatic renal cell carcinoma. While the treatment with TKIs has demonstrated clinical benefit these drugs will eventually fail patients. The potential mechanisms of resistance to TKIs are poorly understood. Experimental Design: To address this question we obtained an excisional biopsy of a skin metastasis from a patient with clear cell renal carcinoma who initially had a response on sunitinib and eventually progressed on therapy. Tumor pieces were grafted subcutaneously in athymic nude mice. Established xenografts were treated with sunitinib. Tumor size, microvascular density and pericyte coverage were determined. Plasma as well as tissue levels for sunitinib were assessed. A tumor derived cell line was established and assessed in vitro for a potential direct antitumor effects of sunitinib. Results: To our surprise, xenografts from the patient who progressed on sunitinib regained sensitivity to the drug. At a dose of 40 mg/kg sunitinib caused regression of the subcutaneous tumors. Histology showed a marked reduction in microvascular density and pericyte dysfunction. More interestingly, histological examination of the original skin metastasis revealed evidence of epithelial-to-mesenchymal-transition while the xenografts showed reversion to the clear cell phenotype. In vitro studies showed no inhibitory effect on tumor cell growth at pharmacologically relevant concentrations. Conclusions: The histological examination in this xenograft study suggests that reversible epithelial-to mesenchymal-transition may be associated with acquired tumor resistance to TKIs in patients with clear cell renal carcinoma. 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 388.
America's Kids Say They Know They Should Eat Better--But Don't Know Why
Authors: K. Smigel
Journal: JNCI Journal of the National Cancer Institute (1989)

Journal Article America's Kids Say They Know They Should Eat Better—But Don't Know Why 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 81, Issue 17, 6 September 1989, Pages 1278–1280, https://doi.org/10.1093/jnci/81.17.1278 Published: 06 September 1989
P721Transgenic mice over-expressing lysyl oxidase exhibit reduced neointimal thickening after carotid artery ligation
Authors: M Galan, A Guadall, M Orriols, R Rodriguez-Calvo, I Marti-Pamies, S Varona, MA Navarro, J Osada, J Martinez-Gonzalez, C Rodriguez
Journal: Cardiovascular Research (2014)

Purpose: Lysyl oxidase (LOX) is an extracellular matrix-modifying enzyme that could play a critical role in vascular remodelling. We have developed a transgenic mouse model that over-expresses LOX in vascular smooth muscle cells (VSMC) to clarify whether LOX could regulate VSMC phenotype and vascular remodelling.
Abstract LB-179: The effects of hypoxia and reactive oxygen species on the methylation status of the polo-like kinases
Authors: Alejandra Ward, John W. Hudson
Journal: Cancer Research (2011)

Abstract The family of polo-like kinases (Plks) consisting of five known members are key regulators of important cell cycle processes, such as mitotic entry, centrosome duplication, spindle assembly, and cytokinesis. Plk1 is typically overexpressed in many cancers, while Plks 2–4 deregulation is often associated with tumorigenesis and malignancy. Plk2 has been shown to be downregulated via promoter DNA hypermethylation in blood neoplasms. Furthermore, in hepatocellular carcinoma (HCC), we and others have shown Plks 2–4 are downregulated through epigenetic modifications, while concurrent decreased Plk 1 promoter methylation was correlated with increased expression. As changes in epigenetic modifications have been associated with external environmental stimuli, we hypothesized that the Plks may be important targets whose disregulation could contribute to malignancy. We therefore examined the status of promoter methylation and expression levels of the Plk family members under hypoxic conditions, and upon exposure to reactive oxygen species (ROS). Interestingly both wild-type and Plk4 heterozygous murine embryonic fibroblasts (MEFs) exposed to ROS displayed significant promoter methylation post treatment. Correspondingly, Plk4 transcript levels were reduced to 90% with no detectable Plk4 protein after exposure to ROS. Since ROS and hypoxic conditions are associated with liver function and normal metabolism, we next examined the promoter methylation status for the individual Plks and other markers in HepG2 and Hep3B liver cell lines. We found increased hypermethylation of the promoter region as well as decreased transcripts levels for both Plk1 and Plk4 post ROS treatment in both cell lines. No detectable methylation changes were detected in SAOS (bone sarcoma, p53 null) cells, while U2OS (p53 wild type) displayed increased methylation and decreased transcript levels. This suggests that the response to ROS might be dependent upon p53 status and origin of cell line. Similar to the case with ROS, hypoxia treatment also induced hypermethylation of Plk4 and decreased in transcripts in both HepG2 and Hep3B cells, while Plk1 levels were only reduced in HepG2 cells. Our results suggest that changes in the cellular environment may be a key regulator of Plk methylation status that in turn leads to deregulation. This has important implications in HCC and other cancers, where these epigenetic alterations could be contributing factors in tumourigenesis and disease progression. 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 LB-179. doi:10.1158/1538-7445.AM2011-LB-179
PWE-179 Gastric polyps: are we following guidelines?
Authors: Q Liu, S Joglekar
Journal: Gut (2012)

<h3>Introduction</h3> Gastric polyps are usually benign and &gt;90% are found incidentally at endoscopy, most common type being fundic gland polyps (FGP).<sup>1</sup> Current guideline advocates biopsy for all types of gastric polyps.<sup>1</sup> Literature review failed to demonstrate a strong link between proton pump inhibitors (PPIs) and FGPs. BSG guidelines also suggest testing and eradicating <i>Helicobacter pylori</i> in patients with hyperplastic polyps. Our study is to analyse gastric polyp subtypes and management. <h3>Methods</h3> Retrospective case note analysis of patients with gastric polyps between January 2009 and December 2010 at James Paget University Hospital. Data collected: Age, gender, endoscopic appearance, histology, association with PPI, management and follow-up. <h3>Results</h3> Total number of patients was 79. Mean age was 67.1 (38–89 yrs). 60.8% were women (n=48). Reflux symptom was the most common indication for OGD (36.7%;n=29). 22.8% (n=18) had single polyp, 58.2% (n=46) had multiple polyps (&gt;3). Majority had sessile appearance at OGD 62.0% (n=49). Most polyps were found in the gastric body 45.5% (n=36), followed by fundus 20.3% (n=16). 54.4% (n=43) polyps were estimated &lt;5 mm, compared to 6.3% (n=5) over 10 mm. Biopsy was performed in 94.9% (n=75) gastric polyps. 2.5% (n=2) polyps were not biopsied due to typical appearance of FGP. Fundic gland polyp (FGP) was the most common histopathological diagnosis (73.4%; n=58), followed by hyperplastic polyp (11.4%; n=9). Neither adenoma nor neoplasic lesions were detected. Information on PPIs use was obtained in only 60.8% patients (n=48): 33.3% (n=16) were not on PPIs; 35.4% (n=17) were on PPIs for an uncertain length of time; 8.3% (n=4) were on PPI9s for &lt;6 months; and 22.9% (n=11) were more than 6 months. The prevalences of FGPs in the above groups were 75%, 76.5%, 75% and 90.0% respectively. 3.8% polyps (n=3) were removed, all of which were greater than 10 mm. <i>H pylori</i> test was performed in 34.2% (n=27) of the patients. All nine patients (100%) with hyperplastic polyps underwent the test. 87.3% (n=69) patients had no follow-up. Only 2.5% (n=2) had repeat OGD. <h3>Conclusion</h3> The local practice in management and follow-up seems to be concordant with the current guidelines. In this study, all gastric polyps were benign, with FGPs as the most frequent diagnosis (73.8%). It raises the question whether a routine biopsy is necessary for polyps with typical FGP appearance. There is no definitive link between PPIs and FGPs (75% FGPs in non-PPI users compared with 80.5% in PPI users). However, the percentage of FGPs presented in long-term PPI users is slightly higher (90%). <h3>Competing interests</h3> None declared. <h3>Reference</h3> 1. <b>Goddard AF</b>, Badreldin R, Pritchard DM, <i>et al.</i> The management of gastric polyps. <i>Gut</i> 2010;<b>59</b>:1270–6.
Langerhans'-Cell Histiocytosis
Authors: Bhakti Mehta, Rajkumar Venkatramani
Journal: New England Journal of Medicine (2014)

A 2-year-old boy presented with refractory eczema and enlarging neck masses. Weight and height were below the fifth percentile. A skeletal survey revealed multiple lytic lesions in the skull and right 10th rib. Lymph-node biopsy results were consistent with Langerhans'-cell histiocytosis.
SAT0353 Association of Gouty Arthritis Severity with Patients’ Mental and Physical Health-Related Quality of Life, Work Productivity and Medical Resource Utilization.
Authors: N. Schlesinger, D. Radvanski, P. Tomanovich
Journal: Annals of the Rheumatic Diseases (2013)

Primary hyperparathyroidism is characterised by high parathyroid hormone (PTH) levels and concomitant hypercalcaemia. Ninety per cent is caused by solitary parathyroid adenomas, 10% by multiple adenomas, hyperplasia and carcinomas. Less than 0.1% of the inferior parathyroid glands are ectopically located. This case is of a 54-year-old woman with hypercalcaemia 3.05 mmol/L and high PTH 22 pmol/L. Scintigraphy and CT scan of the neck in 2009 showed no signs of ectopic tissue. After treatment with Aredia (pamidronate disodium) infusion, calcium decreased to 2.73 mmol/L. In 2010 the serum calcium levels increased again to 3 mmol/L. Repeated CT showed no ectopic tissue. However, revision of the CT by the multidisciplinary team including an experienced endocrine surgeon revealed an ectopic parathyroid gland at the level of the hyoid bone, which was surgically removed in 2011. Preoperatively the PTH level was 16.8 mmol/L, postoperatively it decreased to 2.9 mmol/L, proving a successful excision. In case of suspicion of a parathyroid adenoma a CT of the neck should be thoroughly assessed by a dedicated multidisciplinary team, including the head and neck surgeon, as clinical data and radiological findings must be combined since ectopic parathyroid adenomas are a rare entity. Thereafter the adenoma can be surgically removed and the patient cured.
Test providers should anticipate incidental and secondary findings, says US bioethics commission
Authors: B. Roehr
Journal: BMJ (2013)

Physicians, researchers, and organizations that provide medical testing services directly to consumers should anticipate possible incidental and secondary findings not directly related to the test’s primary purpose, says a new report from the US Presidential Commission for the Study of Bioethical Issues.1

Providers of such tests, ranging from genetic sequencing to brain imaging, should communicate with consumers on an ongoing basis so that consumers can make informed decisions about what tests they should have, what information they wish to receive, and how unexpected findings might be managed.

The commission defined incidental findings as “results that arise outside the …
Cerebellar long-term depression as investigated in a cell culture preparation
Authors: David J. Linden
Journal: Behavioral and Brain Sciences (1996)

Cerebellar long-term depression (LTD) is a form of synaptic plasticity, first described by Ito and co-workers, in which simultaneous activation of two excitatory inputs to a Purkinje neuron, parallel fibers (PFs) and climbing fibers (CFs), results in a sustained depression of PF synaptic drive. The purpose of this target article is not to assess the possible role of this synaptic alteration in motor learning, an issue which is addressed by other authors in this volume, nor is it to provide a detailed summary of the work on cerebellar LTD to this point (see Linden &amp; Connor 1993; Crépel et al. 1993 for review) or to place cerebellar LTD within the context of other forms of persistent synaptic depression that occur within the mammalian brain (see Linden 1994b). Rather, it is to discuss results obtained using a very reduced preparation for the study of LTD, embryonic Purkinje neurons grown in culture and stimulated with exogenous excitatory amino acids, and to consider some advantages and limitations of this approach. Recent work using this preparation has suggested that three processes are necessary for the induction of cerebellar LTD: Ca influx through voltage-gated channels, Na influx through AMPA receptor-associated channels or voltage-gated Na channels, and protein kinase C activation - which is dependent upon activation of the metabotropic glutamate receptor mGluRl. In addition, input-specific induction of LTD has been demonstrated in this preparation Under conditions where both spontaneous and evoked neurotransmitter release are reduced or eliminated, indicating that postsynaptic alterations are sufficient to confer this important computational property.
Financial Implications of Implementing Standards of Care for Diabetes and Pregnancy
Authors: A Elixhauser, J M Weschler, J L Kitzmiller, H W Bennert, D R Coustan, S G Gabbe, W Herman, R C Kaufmann, E S Ogata, J S Marks
Journal: Diabetes Care (1992)

This article examines the financial implications of implementing standards of care for pregnancy among women with diabetes, including both the costs of enhanced treatment and the savings of avoided adverse outcomes. Numerous studies have demonstrated the harmful effects of poor blood glucose control for both mother and fetus. Standards set forth by the American Diabetes Association aim to reduce maternal complications and fetal adverse outcomes, such as congenital malformations. Because the precise configuration of resources required to meet these standards was not outlined in the American Diabetes Association statement, a panel of physicians (all specialists in pregnancy care for women with diabetes) was convened to develop a model program. Implementing such a program during the preconception and prenatal periods will represent an intensification of resource use in the outpatient setting. However, through these preventive measures, medical care costs for maternal and fetal complications can be avoided.
Abstract 215: Soluble guanylyl cyclase α1 and p53 cytoplasmic sequestration: A novel mechanism for p53 down-regulation in prostate cancer
Authors: Lirim Shemshedini, Shuai Gao
Journal: Cancer Research (2011)

Abstract Our lab has identified soluble guanylyl cyclase α1 (sGCα1) as a novel androgen- regulated gene involved in prostate cancer cell proliferation. A well-known biological function of sGCα1 is to heterodimerize with sGCβ1 forming the enzyme sGC, which mediates nitric oxide(NO) signaling. Our published data demonstrated that the sGCα1 effect on prostate cancer cell growth is independent of the classical mediators of NO signaling, suggesting that sGCα1 acts via a novel signaling pathway. Furthermore, sGCα1 expression is highly elevated in prostate tumors and this expression is directly correlated to the progression stage of prostate cancer. Interestingly, we have recently discovered that sGCα1 can inhibit the transcriptional activity of p53 via a mechanism that does not depend on classical mediators of NO signaling. Immunoprecipitation and immunocytochemistry assays have shown an association between sGCα1 and p53 and these data suggest that sGCa1 inhibits p53 by mediating the cytoplasmic sequestration of this tumor suppressor protein, which would represent a previously unknown mechanism for p53 regulation. sGCa1 can also regulate in a gene-specific manner p53-regulated gene expression, targeting genes involved in apoptosis. In addition, sGCa1 makes prostate cancer cells resistant to the chemotherapeutic and apoptosis-inducing drug Etoposide. Finally, analysis of prostate tumors has shown a direct correlation in expression between sGCα1 and p53. Collectively, these data suggest that sGCa1 regulation of p53 activity is important in prostate cancer biology and may represent an import mechanism of p53 down-regulation in those prostate cancers that express significant levels of p53. 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 215. doi:10.1158/1538-7445.AM2011-215
Abstract 5606: Preclinical and clinical development of anti-CD25 recombinant immunotoxin LMB-2 in combination with chemotherapy for the treatment of adult T-cell leukemia
Authors: Rajat Singh, Yu Jian Zhang, Ira Pastan, Robert J. Kreitman
Journal: Cancer Research (2010)

Abstract LMB-2, previously called anti-Tac(Fv)-PE38, is a recombinant immunotoxin containing the variable domains of the anti-CD25 Mab and a truncated form of Pseudomonas exotoxin. LMB-2 binds and internalizes via CD25, and a processed toxin fragment translocates to the cytosol where catalytic ADP-ribosylation leads to cell death. LMB-2 induces complete and partial responses (CR + PR) in patients with CD25+ hairy cell leukemia, and partial responses were reported in other hematologic malignancies including adult T-cell leukemia (ATL). While nearly all ATL cells express CD25 at high levels, clinical efficacy was limited by rapid progression between cycles and immunogenicity. Recently, preclinical studies using the anti-mesothelin recombinant immunotoxin SS1P indicated that soluble receptor is ∼10-fold higher in the interstitial space of the tumor xenograft than in the serum (PNAS, 104:17099, 2007) and that gemcitabine was synergistic against the xenografts when used prior to SS1P to deplete interstitial soluble receptor (Clin Cancer Res, 13:7166, 2007). To determine if soluble CD25 (sCD25) in the interstitial space of tumors could be a limiting factor in the antitumor activity of LMB-2 in ATL, xenografts of CD25+ human ATAC-4 cells were grown subcutaneously in nude mice and harvested so that the serum and intratumoral sCD25 concentrations could be compared. Intratumoral sCD25 concentrations were 21-159 (median 43) ng/ml, compared to between undetectable and 0.33 (median 0.093) ng/ml in serum (p=0.0008, n=8). Thus, intratumoral sCD25 was 86-2200 (median 610)-fold higher than serum sCD25 in this model. To determine if chemotherapy would improve the efficacy of LMB-2 towards these tumors, groups of ATAC-4-bearing mice (tumor implantation day −3) were treated with gemcitabine on days 1 and 3, and then LMB-2 on days 3, 5 and 8. Mice treated on this schedule with gemcitabine 40 mg/Kg x2 and LMB-2 50 ug/Kg x3 had smaller tumors than mice treated with twice the dose of either agent alone, confirming in vivo synergy, with the mechanisms currently under study. A clinical trial in ATL is now underway with fludarabine and cyclophosphamide on days 1, 2, and 3 followed by LMB-2 on days 3, 5 and 7, to determine if chemotherapy can prevent immunogenicity, enhance the antitumor activity of the immunotoxin, and when possible, determine if intratumoral sCD25 is depleted. 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 5606.
EFFECT OF EXTENDED-RELEASE NIACIN ON REACTIVE HYPEREMIA PERIPHERAL ARTERIAL TONOMETRY AND ENDOTHELIAL PROGENITOR CELL MOBILIZATION: INSIGHTS FROM THE ATHEROSCLEROSIS LESION PROGRESSION INTERVENTION USING NIACIN EXTENDED RELEASE IN SAPHENOUS VEIN GRAFTS (ALPINE-SVG) PILOT TRIAL
Authors: Bavana V. Rangan, Anna Kotsia, Aristotelis Papayannis, Ameka Coleman, Hao Xu, Mohammed Alomar, Michele Roesle, Georgios Christopoulos, Daisha Cipher, James de Lemos, Darren McGuire, Milton Packer, Subhash Banerjee, Emmanouil Brilakis
Journal: Journal of the American College of Cardiology (2015)