tbuckley/cabot-search huggingface dataset:
Phase II study of AMG 102, a fully human neutralizing antibody against hepatocyte growth factor/scatter factor, in patients with recurrent glioblastoma multiforme
Authors: D. A. Reardon, T. F. Cloughsey, J. J. Raizer, J. Laterra, D. Schiff, X. Yang, E. Loh, P. Y. Wen
Journal: Journal of Clinical Oncology (2008)

2051 Background: The hepatocyte growth factor/scatter factor (HGF/SF) and its receptor c-Met are implicated in the pathogenesis of glioblastoma multiforme (GBM) through an autocrine pathway, potentially affecting cancer cell survival, invasion, migration, and angiogenesis. In this phase 2 study, AMG 102, a fully human, IgG2, neutralizing antibody that selectively targets HGF/SF, was administered to patients with recurrent GBM to assess its safety and efficacy. Methods: Patients with measurable disease and ≤ 3 relapses or prior systemic therapies were treated with AMG 102 by infusion every 2 weeks (Q2W) until progression, intolerable adverse event, or consent withdrawal. The first 10 mg/kg cohort of 20 patients would be expanded to 40 patients if ≥ 1 response (including minor responses) were observed at week 9. The primary efficacy endpoint is response rate by Macdonald criteria. Results: This report describes the first 20 patients who received AMG 102 at 10 mg/kg: 15 men, mean age 48 ± 12 years, mean 19 ± 10 months since diagnosis, median 2.5 (range, 1–3) prior systemic therapies. In 18 patients with available data, 1 patient had a confirmed partial response and remains on study after 227 days; 1 had a minor response but withdrew after 161 days due to peripheral edema. Two patients had stable disease; 1 withdrew after 219 days (peripheral edema), and the other withdrew after 88 days (deep vein thrombosis [DVT]); 14 patients had progressive disease. Five patients reported grade 3 or 4 treatment-related adverse events (AEs): peripheral edema (n = 2); hypophosphatemia (n = 3), and DVT (n = 1). Grade 1 or 2 treatment-related AEs reported in ≥ 2 patients included nausea (n = 3), diarrhea (n = 2), fatigue (n = 5), dyspnea (n = 2), and dry skin (n = 2). No treatment-related deaths were reported. The dose cohort was opened to the next 20 patients at 10 mg/kg. Conclusions: AMG 102 appeared to be well tolerated at 10 mg/kg IV Q2W in this heavily pretreated population. These results, using a neutralizing antibody highly specific for HGF/SF, suggest that in patients with recurrent GBM, a subpopulation has disease that may be dependent on the c- MET:HGF/SF axis. The study is ongoing with 40 patients treated at 10 mg/kg IV Q2W. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Amgen Amgen
Circadian rhythm of bone turnover markers in breast cancer patients with bone metastases and in control subjects
Authors: D. G. Generali, S. Tedoldi, M. Tampellini, A. Berruti, M. Torta, S. Bonardi, A. Bottini, M. Tucci, M. Milani, A. Angeli, L. Dogliotti
Journal: Journal of Clinical Oncology (2005)

737
Does surgery improve survival?
Authors: Muhammad F Dawwas
Journal: BMJ (2007)

We select the letters for these pages from the rapid responses posted on bmj.com favouring those received within five days of publication of the article to which they refer.Letters are thus an early selection of rapid responses on a particular topic.Readers should consult the website for the full list of responses and any authors' replies, which usually arrive after our selection. cnri/spl Acute bronchiolitis risk of hyponatraemiaBush and Thomson stated that electrolytes should be determined only in infants with bronchiolitis who are dehydrated. 1 However hyponatraemia is seen in up to 33% of children in hospital with this disease. 2It is unrelated to dehydration and has been associated with administration of intravenous fluids together with increased antidiuretic hormone values. 3 4 It can cause generalised tonic-clonic seizures, 2 which may be refractory to anticonvulsants.The National Patient Safety Agency has issued an alert aimed at reducing the risk of hyponatraemia in children -electrolytes should be determined before starting intravenous fluids and at least daily afterwards. 5 Fluids should be restricted in children with hyponatraemia who are receiving intravenous 0.9% saline (with 5% dextrose) and who have high antidiuretic hormone concentrations.
The Role of Pediatricians in the Face of Increasing Domestic Terrorism Threats
Authors: David J. Schonfeld
Journal: JAMA Pediatrics (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Sequence of Events in Experimental Metastases of Walker 256 Tumor: Light, Immunofluorescent, and Electron microscopic Observations&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: D. S. Jones, A. C. Wallace, E. E. Fraser
Journal: JNCI Journal of the National Cancer Institute (1971)

The behavior of Walker 256 tumor cells, reaching the lungs after intravenous inoculation into Sprague-Dawley rats, was studied over a period from a few minutes to 4 days. Serial sections with hematoxylin and eosin, Lendrum's stain for fibrin, and immunofluorescent staining for fibrin were examined, and the same tumor cells were observed by all three methods. Parallel electron microscopic sections followed the progress of similarly injected tumors over the same time period. By all methods it was shown that the cells were arrested singly or in small groups in capillaries and arterioles, and were surrounded by a meshwork resembling fibrin by Lendrum's and immunofluorescent stains, but which appeared only as platelet masses by electron microscopy. Fibrin was identified rarely in the masses by the latter method. The tumor cells remained intravascular for several hours. Platelets disappeared after about 8 hours and there was progressive breaching of the endothelial lining until by 24–48 hours the cells were clearly perivascular and lying in direct apposition to connective tissue. It is suggested that a loose reversible platelet-protein aggregation forms rapidly around the tumor cells, but that stable fibrin is not usually formed with this tumor. During the few hours this aggregation is present the cells breach the endothelium and subsequently become completely perivascular.
NAD(P)H:quinone oxidoreductase 1 expression in human primary melanotic melanomas of the skin
Authors: F. Zappa, F. Cavalli
Journal: Journal of Clinical Oncology (2006)

18018 NAD(P)H:quinone oxidoreductase 1 (NQO1; DT-diaphorase; DTD) is a two-electron reducing enzyme which is often over-expressed in cancers and can activate quinones to form cytotoxic species. This over-expression is used as target in the design of novel anti-cancer drugs. DTD is also expressed in normal tissues, but little is known about its “body mapping”. Because of the dearth of information on the cell-specific expression of DTD in pigment-producing cells of the skin, we analysed its expression in normal and tumoral samples. Twenty skin biopsies of primary malignant melanotic melanomas (ten with vertical invasion, ten with superficial spreading) were analysed by immunohistochemistry. In normal skin DTD expression was weak in all epidermal layers, including normal melanocytes. Malignant melanomas showed a very strong DTD expression in tumoral cells of all samples and in endothelial lining of peri-tumoral vessels. These results suggest that DT-diaphorase may be a new marker that could be useful in determining the extent of a malignant melanocytic lesion, and also tend to support the potential of malignant melanomas as target for DTD-directed antitumour agents. No significant financial relationships to disclose.
Use of the Comprehensive Geriatric Assessment (CGA) in elderly patients (pts) with solid tumors to predict mortality
Authors: F. U. Honecker, U. Wedding, K. Rettig, S. Huschens, C. Bokemeyer
Journal: Journal of Clinical Oncology (2009)

9549 Background: The internet based IN-GHO-Registry, a project of the Initiative for Geriatric Hematology and Oncology, supported by ORTHO BIOTECH, Division of Janssen-Cilag GmbH, Germany, prospectively collects data of elderly cancer pts. We report data from 1130 pts with solid tumors. Results of a CGA, physicians' and pts' judgement of fitness were studied in relation to mortality within 5–7 months. Methods: Demographic data, data on activities of daily living (ADL), instrumental activities of daily living (IADL), Karnofsky-Performance-Statuts (KPS), comorbidity (Charlson score), number of co-medication, mobility (Timed-Up&amp;Go), cognition (MMSE), and depression (SCID screening) were collected. Age, results of CGA, physicians' rating (fit vs compromised vs frail) and pts' self rated fitness for treatment (Likert scale 1= very fit to 6 = very unfit) were analysed for association with death. Follow-up (FU) was scheduled 5–7 months after inclusion. Results: 1130 pts, mean age 76.3 years (SD 4.7; range 69–95), 44% male, were included. Main diagnoses were gastrointestinal tumors (38%), breast cancer (12%), and lung cancer (11%). Physicians rated 58% of pts fit, 37% compromised, and 5% frail. Pts' self rating of fitness: 1 = 19%, 2 = 30%, 3 = 28%, 4 = 17%, 5 = 5%, 6 = 1%. During FU (median 177 days), 272 pts (24%) died. Mean age (76.5 vs. 76.3; p=0.75) was not associated with death. However, sex (male vs female, p&lt;0.001), BMI (24.4 vs 25.9; p&lt;0.001), Charlson-score (6.3 vs 5.5; p&lt;0.001), number of co-medication (4.5 vs 3.7; p&lt;0.001), ADL score (87.9 vs 93.9; p&lt;0.001), IADL score (6.2 vs 7.0; p&lt;0.001), KPS score (75% vs 83%; p&lt;0.001), MMSE (25.6 vs. 26.2; p=0.045), categorical Timed-Up&amp;Go (less than 10s, 10–20s, more than 20s; p&lt;0.001), categorical SCID (0, 1, 2; p=0.012), physicians' rating of fitness (fit, compromised, frail; p&lt;0.001) and mean pts' rating of fitness (3.1 vs. 2.4; p&lt;0.001) were significantly associated with death during FU. Conclusions: Pts characteristics as assessed by CGA and not age are associated with death in elderly pts with solid tumors. [Table: see text]
A Randomized Trial of Phototherapy with Filtered Sunlight in African Neonates
Authors: Tina M. Slusher, Bolajoko O. Olusanya, Hendrik J. Vreman, Ann M. Brearley, Yvonne E. Vaucher, Troy C. Lund, Ronald J. Wong, Abieyuwa A. Emokpae, David K. Stevenson
Journal: New England Journal of Medicine (2015)

Sequelae of severe neonatal hyperbilirubinemia constitute a substantial disease burden in areas where effective conventional phototherapy is unavailable. We previously found that the use of filtered sunlight for the purpose of phototherapy is a safe and efficacious method for reducing total bilirubin. However, its relative safety and efficacy as compared with conventional phototherapy are unknown.
<i>RET </i>rearrangements detected by FISH in “pan-negative” lung adenocarcinoma.
Authors: Marileila Varella-Garcia, Liang Guo Xu, Sakshi Mahale, Eamon M Berge, Chiara Bennati, Anh T. Le, Dara Aisner, Lucio Crinò, Paul A. Bunn, D. Ross Camidge, Robert Charles Doebele
Journal: Journal of Clinical Oncology (2013)

8024 Background: RET rearrangements have recently been reported in NSCLC and there is pre-clinical evidence that RET tyrosine kinase inhibitors (TKIs) block activated RET kinase. Efficient and accurate detection of RET rearrangements are crucial for the success of RET TKIs in clinical trials. RET rearrangements have been detected by specialized sequencing techniques with limited applicability to clinical practice. Methods: A 3-target FISH probe set was developed to detect KIF5B-RET fusions and identify patterns suggestive of RET rearrangements with non-KIF5B partners. 51 lung adenocarcinomas negative for EGFR, KRAS, ALK and ROS1 (36 were also negative for 7 other molecular markers) were investigated. Clinical and demographic characteristics were collected. Results: Eight patients (15%) had rearrangements in the RET gene: 5 with KIF5B-RET fusions, 2 with patterns consistent with the CCDC6-RET fusion, and 1 with extra copies of single 3’RET (loss of 5’RET). Atypical FISH patterns were detected both in RET + and negative specimens suggesting high genomic instability in the KIF5B – RET region. RT-PCR assay determined the exon/fusion variant in 4 cases including 2 patients with K15:R12, 1 with K16:R12 and 1 with C1:R12. Median age at diagnosis was 58.5 in the mutation negative and 63 in the RET+ patients. Both cohorts were predominantly male (66% and 56%, respectively), with a majority of never smokers (59 and 89%, respectively), and stage IV disease at diagnosis (72 and 89%, respectively). Two heavily pretreated RET+ patients had stable disease at their initial restaging scans following treatment with the RET inhibitor vandetanib (radiographic assessment per RECIST 1.1); two others had early radiographic progression with sunitinib. Conclusions: The FISH probe proved efficient to detect RET rearrangements in lung adenocarcinomas, involving KIF5B and non-KIF5B partners. Frequency of RET rearrangements in this enriched lung adenocarcinoma cohort was considerably higher than reported in unselected cohorts. Further molecular analyses are being performed to increase understanding of the natural history of this new molecular subtype of NSCLC. Support: B J Addario Foundation, NCI P50CA058187, NCI CCSG P30CA046934.
THE ROLE OF IMMUNITY IN THE PATHOGENESIS OF EXPERIMENTAL HEMATOGENOUS PYELONEPHRITIS
Authors: Jay P. Sanford, Betty W. Hunter, Lona L. Souda
Journal: The Journal of Experimental Medicine (1962)

Hematogenous pyelonephritis was produced in rats utilizing multiple strains of Escherichia coli, a strain of Klebsiella pneumoniae, and a strain of Proteus mirabilis. Three patterns of hematogenous pyelonephritis occurred which represent an interrelationship between an immune response to the infecting bacteria and the development of obstructive uropathy as a consequence of infection. First, the course of pyelonephritis due to strains of Escherichia coli was acute, self-limited, and associated with the development of circulating agglutinins. Following healing, this pattern of infection was associated with acquired resistance to reinfection with the same bacterial strain. Second, the course of pyelonephritis due to a strain of Klebsiella pneumoniae type C was chronic. This infection was not associated with the production of circulating agglutinins against encapsulated strains. Acquired resistance to reinfection by the homotypic strain could not be demonstrated following eradication of infection but was produced by the passive transfer of concentrated antiserum. Third, pyelonephritis due to Proteus mirabilis was associated with circulating agglutinins and resistance to reinfection with the same organism following eradication of infection, yet the course was chronic. The chronicity appeared to be the consequence of obstructive uropathy resulting from calculi which developed during the course of the infection. Resistance to reinfection was demonstrated in infections with strains of E. coli and P. mirabilis. The resistance is associated with specific immunity as demonstrated by the observation that: (a) it is type-specific, (b) it is of at least 3 months' duration, and (c) it can be passively transferred by means of rabbit antiserum. Since K. pneumoniae failed to evoke capsular antibodies in the rat, resistance to infection with K. pneumoniae was produced only by means of passively transferred concentrated rabbit antiserum and not by prior infection. Immunity can be demonstrated to have a significant role in the pathogenesis of experimental hematogenous pyelonephritis only in the absence of obstructive uropathy.
Demographics of populations at high risk of lung cancer and results of the Early CDT-Lung test.
Authors: J. Mathew, G. Healey, W. Jewell, A. Murray, C. Chapman, L. Peek, A. Barnes, W. Wood, J. F. Robertson, P. Boyle
Journal: Journal of Clinical Oncology (2010)

7033 Background: EarlyCDT-Lung measures autoantibodies (AABs) to six cancer-associated antigens (p53, NY- ESO-1, CAGE, GBU4-5, Annexin1, and SOX2) and has been reported to identify up to 40% of lung cancers, both early- and late-stage disease. Methods: Prospective blood collections (with individual questionnaires) were carried out in three different community-based locations in two countries (US, two sites; UK, one site) in order to assess demographic features of high-risk populations. Some demographic features were not recorded at all sites. For the statistical comparisons, analysis of variance was generally used, taking into account imbalance in subgroup numbers, unevaluable data and multiplicity of testing, where necessary, and with sample-matching, where appropriate. Results: Unmatched Datasets: from separate analyses of the US (Florida n=320, Midwest n=940) and UK (n=2046) datasets there was no difference for any of the AAB assays between (i) males and females, (ii) the main ethnic groups (US only) for participants in samples collected in Florida and the Midwest, and (iii) the presence or absence of benign autoimmune diseases (UK data only). There was evidence for an effect of age for some antigens, with mean AAB levels rising with age (especially >70yrs). This may be confounded by the fact that the incidence of cancer also increases with age. Further investigation is required. Matched Datasets: for sets of samples matched for age, sex, and smoking, there was no significant difference for any autoantibody assay between (i) US (n=353) and UK (n=353) high-risk individuals and (ii) within US (Florida, n=275 and Midwest, n=275) samples. Conclusions: Within a high risk population the demographic features described above should not be used to exclude individuals from AAB testing as an aid to early detection of lung cancer. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Oncimmune Oncimmune Oncimmune Oncolytics Biotech
Identification of prognostic factors in patients with brain metastases: A review of 493 patients
Authors: B. P. Baltalarli, D. Yalman, O. Akagündüz, Z. Ozsaran, Y. Anacak, S. Ozkok, M. Esassolak, A. Aras, A. Haydaroglu
Journal: Journal of Clinical Oncology (2006)

11516 Background: Choice of treatment for an individual patient with brain metastases is based on a number of factors: number and localization of brain metastases, systemic tumor activity, performance score, and age are major determinants for selection of treatment modality. Future trials in patients with brain metastases depend on selection of patients with favorable prognosis to allow adequate long-term follow-up to draw conclusions about survival and late toxicity, further stressing the importance of prognostic parameters. Our aim is to report the outcome of patients with brain metastases from solid tumors treated with whole brain radiotherapy (WBRT) in a single institution and identify the prognostic subgroups who will benefit from treatment. Methods: The records of 493 patients with brain metastases who had been admitted for WBRT in the Department of Radiation Oncology in Ege University Hospital between January 1997 and December 2002 was retrospectively evaluated. WBRT at this institution comprised of parallel opposed lateral fields, dosed to the midplane in a cobalt 60 teletherapy device. Radiotherapy fractionation were 10 fr. × 3 Gy, 5 fr × 4 Gy and 2 fr. × 8 Gy. Survival was calculated using the Kaplan-Meier method. Cox regression modeling was used for multivariate analysis and prognostical factors were determined on the basis of log rank test (SPSS 10.00 version). Results: Clinical response evaluation revealed that 254 patients (51%) had response to tretament whereas 104 patients (21.1%) had stable response and the other 43 patients (8.7%) had progressive disease.The median survival was 3 months (1–62 months) and 6 months survival was 41% and one year survival was 19%. Univariate analysis revealed that prognostical factors for survival were younger age (age &lt;57) (p=0.043), female gender (p=0.019) and operation (p=0.0004), and for multivariant analysis female gender (p=0.027) and operation were determined (p=0.000). Conclusion: The prognosticators for survival in this retrospective analysis for patients with brain metastases are age, gender and operation. These factors affecting survival must be taken into consideration when the therapeutic management is to be made. And they may allow better selection of individual treatments. No significant financial relationships to disclose.
O056 : Ledipasvir/sofosbuvir treatment results in high SVR rates in patients with chronic genotype 4 and 5 HCV infection
Authors: A. Abergel, V. Loustaud-Ratti, S. Metivier, D. Jiang, K. Kersey, S.J. Knox, P.S. Pang, D. Samuel, T. Asselah
Journal: Journal of Hepatology (2015)
Ultrastructural Concomitants of Sodium Butyrate-Enhanced Ectopic Production of Chorionic Gonadotropin and Its Alpha Subunit in Human Bronchogenic Carcinoma (ChaGo) Cells
Authors: T S Tralka, S W Rosen, B D Weintraub, J M Lieblich, L W Engel, B K Wetzel, E W Kingsbury, A S Rabson
Journal: JNCI Journal of the National Cancer Institute (1979)

Sodium butyrate treatment of cultures of ChaGo (human lung cancer) cells resulted in increased production of human chorionic gonadotropin (hCG) and its alpha subunit (hCG-alpha) and induced a variety of morphologic changes. Elongation and flattening of cells were seen by light microscopy. Immunocytochemistry with antisera against hCG and against hCG-alpha showed an increase in cells containing stainable hCG-alpha. Scanning electron microscopy demonstrated enhanced adhesion of cells to glass cover slips, with elongation, flattening, and decreased cytoplasmic blebs. Ultrastructural changes were examined by transmission electron microscopy and evaluated quantitatively by an unbiased observer. Significant findings included increases in perinuclear tonofilaments, smooth endoplasmic reticulum vesicles, dense mitochondrial inclusions, and lipid granules, as well as decreases in intercellular desmosomes, free polyribosomes, mitochondrial dense granules, and Golgi complexes. The most notable change, a marked decrease in condensed chromatin clumps, may have reflected a butyrate-induced biochemical modification of chromatin leading to enhanced accessibility of certain genes for transcription.