tbuckley/cabot-search huggingface dataset:
Induction of Tubular Structures in the Endoplasmic Reticulum of Human Lymphoid Cells by Treatment With 5-Bromo-2′-Deoxyuridine
Authors: Philip M. Grimley, David W. Barry, Zsuzsa Schaff
Journal: JNCI Journal of the National Cancer Institute (1973)

Treatment of suspension cultures of human lymphoid cells with the halogenated pyrimidine 5-bromo-2′-deoxyuridine (BUDR) induced the formation of 20-28 nm diameter tubules within the endoplasmic reticulum. Up to 14% of cell sections examined by electron microscopy were involved. This effect was dependent upon the concentration of BUDR in the culture medium and the duration of treatment. The tubular structures "appeared within 72 hours after suspension of the lymphoid cells in 20 µg/ml BUDR. The morphological response to BUDR was completely blocked by simultaneous treatment of the cultures with excess thymidine (20 × 10-5M). The cell lines tested originated from patients with infectious mononucleosis (PGLC) and Burkitt's lymphoma (Raji). These lines were known to be infected by Epstein-Barr virus, but herpestype nucleocapsids or virions were never identified in the cells treated with BUDR. Ultrastructurally, the BUDR-induced tubules could not be distinguished from previously described “tubuloreticular structures” which appear clinically in the lymphocytes or vascular endothelial cells of patients with virus infection, systemic autoimmune diseases, or cancer, and which also occur spontaneously in some lymphocyte cultures from symptom-free individuals. Although the identity of tubuloreticular structures in patients and in vitro remains to be established by other than morphologic criteria, BUDR treatment of lymphoid cell cultures demonstrates that such structures can form selectively in response to a specific stimulus and provides an experimental model for further investigations.
Salivary IgA and IgG antibodies to bullous pemphigoid 180 noncollagenous domain 16a as diagnostic biomarkers in mucous membrane pemphigoid
Authors: S. Ali, C. Kelly, S.J. Challacombe, A.N.A. Donaldson, J.K.G. Dart, M. Gleeson, J.F. Setterfield
Journal: British Journal of Dermatology (2015)

Mucous membrane pemphigoid (MMP) is an uncommon mucocutaneous immunobullous disorder. Use of saliva for diagnosis by enzyme‐linked immunosorbent assay (ELISA) using the noncollagenous (NC) domain 16a of bullous pemphigoid antigen II (BP180) is not well described. To establish whether whole or parotid saliva is a suitable alternative to serum for diagnosis of MMP. Precoated BP180‐NC16a ELISA plates were used to test serum, and whole and parotid saliva for IgG, IgA and secretory IgA antibodies. Patients with MMP (n = 64) provided matched serum and whole saliva. In addition 18 of the MMP patients also provided matched parotid saliva. Healthy controls (n = 50) provided matched serum and whole saliva and 6 of these additionally provided matched parotid saliva. An additional 16 disease controls provided matched serum, and whole and parotid saliva. In whole saliva, IgG antibodies were detected in 11/64 (17%), IgA in 23/64 (36%) and a combined positivity in 29/64 (45%). In parotid saliva, IgA antibodies were found in 8/18 (44%). Serum IgG antibodies were detected in 27/64 (42%), serum IgA antibodies in 18/64 (28%) and a combined positivity in 33/64 (52%). Combined use of serum and saliva increased detection of specific antibodies by 30%. Control samples were all negative (positive predictive value of 100% for all tests). The negative predictive values were 62% for IgA saliva, 65% for IgG serum, 59% for IgA serum and 56% for IgG saliva. IgG and IgA antibodies may provide a suitable diagnostic marker in MMP. Assay of salivary IgA antibodies to NC16a offers a similar diagnostic predictive value to serum.
Acute nonlymphoblastic leukemia in infants: clinical presentation and outcome.
Authors: C H Pui, D K Kalwinsky, M J Schell, C A Mason, J Mirro, G V Dahl
Journal: Journal of Clinical Oncology (1988)

The presenting features and clinical outcome of acute nonlymphoblastic leukemia (ANLL) in infants and older children were compared to identify any differences that might suggest methods to improve therapy. Twelve of the 29 infants were boys and 17 were girls, with ages ranging from two days to 12 months (median, 7 months). By comparison with 222 patients greater than 1 year of age, infants were significantly more likely to have monoblastic or myelomonoblastic leukemia (P less than .0001), chloroma (P less than .0001), marked hepatomegaly (P = .001), and high leukocyte count (P = .005) and were less likely to have Auer rods (P less than .001). Each of these features except leukocyte count showed an association with infant ANLL in a multivariate analysis. Twenty-four (83%) of the infants attained a complete remission, a rate that was not significantly different from that of the older children. Even though infants had a significantly higher CNS relapse rate (P = .003), their event-free survival times were no different than those of older children (P = .74). Ten of the infants remain in initial complete remission for 5+ to 112+ months (median, 52+ months). Infants with ANLL did not have a poorer prognosis than older patients in our study; future protocols for this age group should emphasize more effective systemic therapy, preferably including an epipodophyllotoxin, as well as improved treatment for subclinical CNS leukemia.
Abstract A33: Combinatorial targeting of tumor-associated macrophages/ microglia and radiotherapy in gliomas
Authors: Leila Akkari, Daniela F. Quail, Marsha L. Quick, Jason T. Huse, James C. Sutton, Johanna A. Joyce
Journal: Cancer Research (2015)

Abstract Eighty percent of tumors that develop in the central nervous system are malignant gliomas, with over half being glioblastoma multiforme (GBM), the most aggressive form of this disease. Unfortunately, there have been minimal improvements in the survival of patients with GBM and these tumors remain essentially incurable. Even following treatment with standard of care therapy (surgery, radiation and temozolomide), the overall 5-year survival rate of patients diagnosed with GBM is less than 5%, highlighting the urgent need for novel and alternative therapeutic strategies to treat GBM. In GBM patients and mouse models of the disease, the major non-cancerous cell type in the glioma microenvironment is tumor-associated macrophages/microglia (TAMMs). TAMMs can account for as much as 30% of the tumor mass in human GBM, and their accumulation is associated with poor patient prognosis. We previously used an inhibitor of colony stimulating factor 1 receptor (CSF-1R), BLZ945, to target macrophages in the RCAS-PDGF-B; nestin-TVA, Ink4a/Arf null mouse model of gliomagenesis, which faithfully recapitulates the hallmarks of human GBM. We found that CSF-1R inhibition dramatically improves survival in a long-term intervention trial and markedly regresses established high-grade lesions. To determine the translational clinical potential for CSF-1R inhibition, we designed preclinical trials in combination with radiation, which is part of the standard treatment for GBM patients. We treated established GBMs with fractionated radiation concomitant with acute, short-term BLZ945 treatment and observed that the overall survival of animals was significantly extended compared to single treatment modalities. Moreover, incorporating long-term treatment with BLZ945 in tumors treated with fractionated radiation lead to a dramatic reduction in tumor recurrence, suggesting that reversing cancer-induced M2 macrophage programming has the potential to render gliomas more prone to response to radiotherapy. Interestingly, treatment of IR-resistant gliomas with BLZ945 de novo resulted in efficient regression of the disease, which may have important translational implications. We are currently examining the molecular mechanisms by which re-educating TAMMs increases radiation sensitivity. Together these results demonstrate critical roles for CSF1R-dependent TAMMs in promoting glioma malignancy, and highlight the clinical potential for CSF-1R inhibitors. Citation Format: Leila Akkari, Daniela F. Quail, Marsha L. Quick, Jason T. Huse, James C. Sutton, Johanna A. Joyce. Combinatorial targeting of tumor-associated macrophages/ microglia and radiotherapy in gliomas. [abstract]. In: Proceedings of the AACR Special Conference: Advances in Brain Cancer Research; May 27-30, 2015; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2015;75(23 Suppl):Abstract nr A33.
Incidence of Lung Adenocarcinoma Biomarker in a Caribbean and African Caribbean Population
Authors: Nicolas Leduc, Christelle Ahomadegbe, Moustapha Agossou, Aude Aline-Fardin, Linda Mahjoubi, Leïla Dufrenot-Petitjean Roget, Nathalie Grossat, Vincent Vinh-Hung, Aude Lamy, Jean-Christophe Sabourin, Vincent Molinié
Journal: Journal of Thoracic Oncology (2016)
Cleavage of Na+ channels by calpain increases persistent Na+ current and promotes spasticity after spinal cord injury
Authors: Cécile Brocard, Vanessa Plantier, Pascale Boulenguez, Sylvie Liabeuf, Mouloud Bouhadfane, Annelise Viallat-Lieutaud, Laurent Vinay, Frédéric Brocard
Journal: Nature Medicine (2016)
Simultaneous Analysis of Different Tumor Types in a Long-Term Carcinogenicity Study With Scheduled Sacrifices
Authors: J Wahrendorf
Journal: JNCI Journal of the National Cancer Institute (1983)

A statistical analysis of a long-term carcinogenicity study with noninbred CF-1 mice exposed to DDT for different durations of time is presented. The experiment included a high proportion of animals with scheduled sacrifices and thus permitted the use of statistical models for tumor prevalence and lethality. Three types of tumors, lymphomas and lung and liver tumors, were considered. The analysis attempted to model the joint behavior of these tumors in relation to time and treatment group. An apparently negative association in the occurrence of lymphomas and liver tumors was confirmed through separate analyses by accounting effectively for intercurrent mortality.
Preclinical study of a novel, non-steroidal, plant-derived, anti-inflammatory compound for the treatment of airway disease
Authors: Philippe Gevaert, Joke Patou, Thibaut Van Zele, Gabriële Holtappels, Karolien De Bosscher, Wim Vanden Berghe, Guy Haegeman, Claus Bachert
Journal: Allergy (2007)
68Ga-PSMA-PET/CT in Patients With Biochemical Prostate Cancer Recurrence and Negative 18F-Choline-PET/CT
Authors: Christina Bluemel, Markus Krebs, Bülent Polat, Fränze Linke, Matthias Eiber, Samuel Samnick, Constantin Lapa, Michael Lassmann, Hubertus Riedmiller, Johannes Czernin, Domenico Rubello, Thorsten Bley, Saskia Kropf, Hans-Juergen Wester, Andreas K. Buck, Ken Herrmann
Journal: Clinical Nuclear Medicine (2016)

Investigating the value of Ga-PSMA-PET/CT in biochemically recurring prostate cancer patients with negative F-choline-PET/CT.One hundred thirty-nine consecutive patients with biochemical recurrence after curative (surgery and/or radiotherapy) therapy were offered participation in this sequential clinical imaging approach. Patients first underwent an F-choline-PET/CT. If negative, an additional Ga-PSMA-PET/CT was offered. One hundred twenty-five of 139 eligible patients were included in the study; 32 patients underwent additional Ga-PSMA-PET/CT. Patients with equivocal findings (n = 5) on F-choline-PET/CT and those who declined the additional Ga-PSMA-PET/CT (n = 9) were excluded. Images were analyzed visually for the presence of suspicious lesions. Findings on PET/CT were correlated with PSA level, PSA doubling time (dt), and PSA velocity (vel).The overall detection rates were 85.6% (107/125) for the sequential imaging approach and 74.4% (93/125) for F-choline-PET/CT alone. Ga-PSMA-PET/CT detected sites of recurrence in 43.8% (14/32) of the choline-negative patients. Detection rates of the sequential imaging approach and F-choline-PET/CT alone increased with higher serum PSA levels and PSA vel. Subgroup analysis of Ga-PSMA-PET/CT in F-choline negative patients revealed detection rates of 28.6%, 45.5%, and 71.4% for PSA levels of 0.2 or greater to less than 1 ng/mL, 1 to 2 ng/mL, and greater than 2 ng/mL, respectively.The sequential imaging approach designed to limit Ga-PSMA imaging to patients with negative choline scans resulted in high detection rates. Ga-PSMA-PET/CT identified sites of recurrent disease in 43.8% of the patients with negative F-choline PET/CT scans.
Renal cell carcinoma: treatment with recombinant interleukin-2 plus beta-interferon.
Authors: R L Krigel, K A Padavic-Shaller, A R Rudolph, M Konrad, E C Bradley, R L Comis
Journal: Journal of Clinical Oncology (1990)

Preclinical data have demonstrated synergy between interleukin-2 (IL-2) and beta-interferon (IFN-beta) in stimulating natural-killer (NK) cell activity and in increasing expression of IL-2 receptors. Based on results of a phase I trial, a combination of IL-2 and IFN-beta was administered three times weekly by intravenous (IV) bolus injection with 5 x 10(6) Cetus U/m2 of IL-2 and 6 x 10(6) U/m2 of IFN-beta to 24 patients with advanced renal cell carcinoma (RCC). Of 22 assessable patients there were six (27%) objective responses including one complete remission (CR) and five partial responses (PRs). There were three minor responses (MRs), 11 stable disease (SD), and two progressive disease (PD). Two of the objective responses have continued for almost 2 years. Response sites include lymph nodes, lungs, and bone. Toxicities requiring dose reduction include arthralgia, weight loss, fatigue, decreased performance status, depression, and hypotension. Five of 10 patients who had a prior nephrectomy without local recurrence achieved an objective response as compared with only one of 12 without a prior nephrectomy or with a local recurrence (P = .04). Mean peak lymphokine-activated killer (LAK) cell activity of the objective responders was 88 lytic units (LU) as compared with 4 LU in the nonresponders (P = .01). Mean peak NK cell activity was 288 LU in the objective responders as compared with 100 LU in the nonresponders (P = .10).(ABSTRACT TRUNCATED AT 250 WORDS)
<i>Saccharomyces cerevisiae</i> as delivery vehicle for a NY-ESO-1 protein vaccine
Authors: C. Renner, G. Held, F. Neumann, S. Kleber, M. Thiel, J. Karbach, E. Jäger, S. Strahl, A. Wadle
Journal: Journal of Clinical Oncology (2006)

2578 Background: Vaccine strategies that target or activate dendritic cells in order to elicit potent cellular immunity are currently the subject of intense research. Here we report that genetically engineered yeast expressing the full-length tumor associated antigen NY-ESO-1 are a versatile host for protein production eliciting MHC class I and II T-cell responses. Methods: The pYD1 yeast display vector was chosen for full length NY-Eso-1 protein (pNY-ESO-1) expression. NY-ESO-1 and SSX-2 (as control) protein were affinity purified on. IFN-g ELISPOT assays were performed in triplicates on nitrocellulose-lined 96-well plates. MHC class I cross-presentation of peptide epitopes was demonstrated by blocking T-cell responses against DCs. For this purpose, antigen or peptide pulsed DCs were labeled with different doses (100, 10, 1 μg/ml) of antibodies specific for HLA-A2/peptide complexes (HLA-A2/ NY-Eso-1 157–165 ; 3M4E5) or an irrelevant antibody (specific for HLA-A2/IMP 58–66 ) as control. Results: Highest level of NY-ESO-1 expression was detected on the cell wall of wt EBY100 strain with lower expression levels on PMT deficient strains PMT-2 and PMT-4. After protein feeding of immature DCs, NY-ESO-1 157–165 peptide cross-presentation was detected by 3M4E5 and an antigen-specific CD8+ T cell clone. There was a strong positive correlation between the amount of Aga2p-NY-ESO-1 protein (0–15μg/ml) and peptide presentation. Specific T-cell recognition of NY-Eso-1 157–165/HLA-A2 complexes was validated by blocking experiments with Fab 3M4E5. Pre-incubation of protein fed DCs with the antibody at different concentrations (0–100 μg/ml) resulted in a significant reduction (p&lt; 0.05) of spot numbers. Efficient presentation and T-cell recognition of epitope 157–165 was only adequately detectable when protein produced by EBY100 wt yeast strain was used (p &lt; 0.05). MHC class II presentation was studied in an autologous setting using a T-cell line recognising the NY-ESO-1 157–170 in HLA-DP4 context revealing that NY-ESO-1 protein produced in yeast was efficiently taken up and presented. Conclusions: Together, these data add further evidence that yeast expressing recombinant proteins can be used for vaccine purposes and that antigen uptake in APC depends on glycoslation of yeast expressed antigens. No significant financial relationships to disclose.
Codon 618 mutation of the RET protooncogene in exon 10 is a good indication of prophylatic thyroidectomy for patients with familial medullary thyroid cancer
Authors: Y. Lee, H. Park, S. Hwang, J. Jung, J. Lee, Y. Eun, J. Shin
Journal: Journal of Clinical Oncology (2008)

17014 Background: FMTC is defined as the presence of MTC in kindred with four or more affected members and with objective evidence of the absence of adrenal and parathyroid gland involvement. An identifiable RET mutation can be detected in about 85% of FMTC families. The majority of germline mutations in FMTC have been found in exons 10 and 11 of the RET proto-oncogene, specifically within the cysteine codons 609, 611, 618, 620, and 634. In this study we screened members of a large Korean family that had a history of FMTC by genetic method and propose a therapeutic approach in managing the disorder. Methods: The large family consists of 3 generations with a total 30 individuals. There was a history of MTC in five members of the family. The index case was a 67-year-old woman who underwent total thyroidectomy with both modified radical neck dissection at the age of 48, for anterior neck mass presented 10 years earlier. DNA of the index case was first screened by looking for RET proto-oncogene mutations in exons 10, 11, 13, 14, 15 and 16, where most of the RET mutations were found in FMTC. In the rest of the individuals, only exon 10 was analysed. Data collection and analysis were performed on an automated DNA sequencer (Model 310, Applied Biosystems). Results: Genetic analysis in the index case revealed a missense TGC ⟶AGC mutation at codon 618 in the exon 10 of the RET proto-oncogene. This transversion leads to the substitution of cysteine with serin. The mutation was detected in all five MTC patients as well as in 6 asymptomatic relatives. The mutation shows a wide clinical heterogeneity, as there are carrier patients with age of diagnosis ranging from 9 to 67 years. Thyroid USG was performed for screening in asymptomatic gene carriers. Three of them were diagnosed MTC and one had benign goiter. Three patients with MTC underwent total thyroidectomy with central or lateral neck dissection. Conclusions: The codon 618 mutation of the RET protooncogene in exon 10 presents with a high penetrance and 100% accordance between presence of the disease and gene carrier status. For minimizing disease-related morbidity, total preventive thyroidectomy has been strongly recommended in all carriers of RET genetic defects in the early life time. No significant financial relationships to disclose.
AB0092 Sideritis Scardica Extract Prevents Bone Loss in Ovariectomized Rats
Authors: I. Jeremic, D. Petrovic, M. Zivkovic, S. Petricevic, V. Tadic, M. Petronijevic, Z. Stanojevic, V. Trajkovic, M. Sefik-Bukilica, K. Gosic, A. Isakovic
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Osteoporosis is the most common metabolic bone disease. Postmenopausal loss of estrogen is a major risk factor. <h3>Objectives</h3> To assess if total ethanolic extract of <i>Sideritis scardica</i> could prevent osteoporosis in ovariectomized female rats. <h3>Methods</h3> Female Wistar rats were divided in three groups: I-sham operated (control), II-ovariectomized-OV and III-ovariectomized, treated orally with <i>S.scardica</i> extract (300 mg/kg) during 20 weeks-OVT. In 18th experimental week oral glucose tolerance test has been performed, as well measurement of bone mineral density-BMD. After killing, femurs, plasma and erytrocytes were isolated. The following parameters were measured: morfometric bone parameters, wet and dry bone mass, biomechanical testig (three point flexural test), Ca and P in urine and plasma, alkaline phosphatase in plasma, malondialdehyde, catalase activity, reduced gluthation (GSH), total SH groups, free fatty acids and fructozamines. <h3>Results</h3> There was no significant difference in Ca and P concentration in plasma between groups, but urinary Ca and P were significantly higher in OV rats (Ca 0.67±0.24 mM, P 3.29±0.77 mM) in comparison to control (Ca 0.434±0.21 mM, P 2.32±1.00 mM) and OVT group (Ca 0.52±0.19 mM, P 2.89±0.42 mM) (p&lt;0.05). Osteocalcin levels were higher in OV group than in control and OVT group, while ALP was higher in OVT group in comparison to OV and control group. OV rats had decreased proximal width of femoral neck (7.38±0.45 mm) in comparison to control (7.55±0.51mm), while OVT group had even greater width than control group (7.73±0.38mm) (p&lt;0.05). OV animals had lower BMD on spine, hip, pelvis, legs and total BMD in comparison to control group, while treated animals did not have different BMD from control. Ultimate load was for control 3930,6±82.4 N/m<sup>2</sup>, for OV group 2726.68±93.4 N/m<sup>2</sup> and for OVT group 3257.2±86.5 N/m<sup>2</sup> (p&lt;0.01). The ratio between wet and dry bone mass 77.97% in control, 72.81% in OV and 75.28% u OVT group. OVT rats showed much better oral glucose tolerance in comparison to control and OV group (p&lt;0.05) and oxydative stress parameters was significanty better in OVT than in OV group (lower MDA, higher catalase, SH groups and GSH). Free faty acids and fructozamines also were lower in OVT than in OV group (p&lt;0.05). <h3>Conclusions</h3> <i>S. scardica</i> extraxct prevents bone loss in ovariectomized rats, increases bone resistance to mechanical load and reduces cardiovascular metabolic risc factors associated with menopause. <h3>Disclosure of Interest</h3> None declared