tbuckley/cabot-search huggingface dataset:
Biological Properties of Three Variants of Rous Sarcoma Virus
Authors: R M DOUGHERTY, P J SIMONS, F C CHESTERMAN
Journal: JNCI Journal of the National Cancer Institute (1963)

The responses to 3 antigenic variants of Rous sarcoma virus have been compared in 4 host systems. The strains are designated RSV(B), RSV(H), and RSV(29). On the chorio-allantoic membrane, RSV(B) induced relatively opaque pocks about 1.5 times the diameter of those initiated by the other 2 strains. Histologic examination showed that pocks were qualitatively similar with all 3 strains, but a greater proportion of those induced by RSV(B) showed involvement of the mesoderm and entoderm. Cornification of the ectoderm was more frequent with RSV(29) than with the other strains. Tissue cultures of chick embryo fibroblasts infected with RSV(B) or RSV(29) developed typical round cell foci, and plating efficiency in the tissue culture assay was high. With RSV(H), tissue cultures developed diffuse foci of elongated cells, which were impossible to count accurately, and plating efficiency was 10 percent or less compared with the chorio-allantoic membrane assay. In 7- to 8-week-old turkeys, RSV(B) and RSV(29) induced tumors that increased in size throughout a 10-week period. By 10 weeks, more than 50 percent of the birds infected with RSV(B) had gross tumors at sites other than the point of inoculation, but none of the turkeys infected with RSV(29) developed secondary tumors in this period. Turkey tumors induced by RSV(H) grew for about 2 weeks, then rapidly regressed, and gross metastases were not seen. The responses of 1-week-old Brown Leghorn chickens to all 3 strains were similar with respect to latent period of tumor response after use of both high and low doses of virus. All tumor growth rates were the same, although RSV(B) tumors reached somewhat larger size. The virus content of RSV(B) tumors was greater than that of tumors induced by the other 2 strains. Histologically, tumors induced by the 3 viruses were identical.
Cell kinetics of human ovarian cancer with in vivo administration of bromodeoxyuridine
Authors: E. Erba, M. Giordano, M. Danova, G. Mazzini, P. Ubezio, V. Torri, C. Mangioni, F. Landoni, P. Bolis, P. Tenti, M. Franchi, L. Babilonti, A. Riccardi, M. D'Incalci
Journal: Annals of Oncology (1994)
Results of the first phase I clinical trial of the novel Ii-key hybrid preventive HER2/neu peptide (AE37) vaccine: United States Military Cancer Institute Clinical Trials Group Study I-03
Authors: L. C. Benavides, J. P. Holmes, J. D. Gates, M. G. Carmichael, M. T. Hueman, E. A. Mittendorf, E. von Hofe, S. Ponniah, G. E. Peoples
Journal: Journal of Clinical Oncology (2008)

3016 Background: HER2/neu is overexpressed in breast cancer (BCa) and is the source of immunogenic peptides. CD4+ T helper peptides for HER2/neu are being evaluated in vaccine trials. The addition of Ii-Key, a 4-amino-acid LRMK modification, increases vaccine potency when compared to unmodified class II epitopes. We present the results of the first human Phase I trial of the Ii-Key hybrid HER2/neu peptide (AE37) vaccine in disease-free, node-negative BCa patients. Methods: The dose-escalation trial included 5 dose groups, to determine safety and optimal dose of the hybrid peptide (100mcg; 500 mcg; 1,000mcg) and GM-CSF (range 0–250mcg). In the event of significant toxicity, GM-CSF (or peptide in the absence of GM-CSF) was reduced by 50%. Immunologic response was monitored by DTH and 3H-thymidine proliferative assays for both the hybrid AE37 (LRMK + HER2/neu:776–790) and AE36 (unmodified HER2/neu:776–790). Results: All 15 patients completed the trial with no grade 3–5 local or systemic toxicities. Dose reductions occurred in 47% of patients for local reactions ≥100mm or grade 2 systemic toxicities. The second group (peptide=500mcg, GM-CSF=250mcg) all required dose reductions prompting peptide-only inoculations in the third group (peptide=1,000mcg, GM-CSF=0mcg). AE37, with and without GM-CSF, elicited dose-dependent immunologic responses in vitro and in vivo to both AE37 and AE36 albeit AE37 responses were more robust. Assessing both toxicities and immunologic responses, the hypothesized optimal biologic dose was determined as peptide=500mcg, GM-CSF=62.5mcg, in 6 monthly injections. Conclusions: The hybrid AE37 vaccine appears safe and well tolerated with minimal local or systemic toxicity if properly dosed. AE37 is capable of eliciting HER2/neu-specific immune responses, even without the use of an adjuvant. This trial represents the first human experience with the Ii-Key modification, and to our knowledge, AE37 is the first peptide-based cancer vaccine to show potency in the absence of an immunoadjuvant. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Antigen Express, Inc. Antigen Express, Inc. Antigen Express, Inc.
Reply to Stephen B. Williams and Ashish M. Kamat's Letter to the Editor re: Samantha Cambier, Richard J. Sylvester, Laurence Collette, et al. EORTC Nomograms and Risk Groups for Predicting Recurrence, Progression, and Disease-specific and Overall Survival in Non–Muscle-invasive Stage Ta–T1 Urothelial Bladder Cancer Patients Treated with 1–3 Years of Maintenance Bacillus Calmette-Guérin. Eur Urol 2016;69:60–9
Authors: Richard Sylvester, Paolo Gontero, Jorg Oddens
Journal: European Urology (2016)
Usefulness of indium-111 antimyosin scintigraphy in confirming myocardial injury in patients with anthracycline-associated left ventricular dysfunction
Authors: R.A. Valdés Olmos, W.W. ten Bokkel Huinink, R.F.A. ten Hoeve, H. van Tinteren, P.F. Bruning, B. van Vlies, C.A. Hoefnagel
Journal: Annals of Oncology (1994)
Phase I dose-escalation study of AZD7762 in combination with gemcitabine (gem) in patients (pts) with advanced solid tumors.
Authors: E. A. Sausville, P. LoRusso, M. A. Carducci, P. N. Barker, F. Agbo, P. Oakes, A. M. Senderowicz
Journal: Journal of Clinical Oncology (2011)

3058 Background: AZD7762, a potent Chk1/Chk2 inhibitor, has shown chemosensitizing activity with gem in preclinical xenograft studies. Methods: This open-label, dose-escalation (3+3 design) study evaluated the safety, tolerability and PK of AZD7762 (6–40 mg iv) alone and combined with gem (750 or 1000 mg/m2 iv) (NCT00413686). Pts received AZD7762 alone on days 1 and 8 (Cycle 0) followed by 7 days’ observation, then AZD7762 + gem on days 1 and 8 of a 21-day cycle. Results: 42 pts (mean age 58 years) received AZD7762 + gem. Colorectal (n=11) and lung (n=10) were the most common primary tumor sites. Median exposure to AZD7762 was 43 days (range 1–318). Cardiac dose-limiting toxicities (DLTs) occurred in 2 pts during Cycle 0 at AZD7762 doses of 32 mg (grade [Gr] 3 asymptomatic elevated troponin I) and 40 mg (Gr 3 myocardial ischemia); both resolved following AZD7762 discontinuation. Two pts had non-cardiac DLTs in Cycle 1; 1 in the 32 mg cohort (Gr 3 vomiting/nausea) and 1 in the 40 mg cohort (Gr 4 neutropenia). Overall, fatigue (n=17) and nausea, neutropenia and pyrexia (n=11 each) were the most common AEs (no neutropenia reported in Cycle 0). In total, 26 pts had a Gr ≥3 AE (10 causally related to AZD7762 and 16 to gem), the most common being neutropenia (n=7) and hyperglycemia (n=3). AZD7762 exposure (Cmax, C24, AUC) increased in a linear and dose-proportional manner over the dose range studied. Gem did not appear to affect the PK of AZD7762. AZD7762 t½ ranged from 8–16 h for AZD7762 alone and 6–18 h for AZD7762 + gem. Plasma concentrations at doses >21 mg were consistent with those biologically effective in preclinical studies. Two pts with NSCLC (6 mg and 9 mg cohorts) had a partial response (RECIST); both were gem naive. Conclusions: The MTD of AZD7762 in combination with gem 1000 mg/m2 was 30 mg. Pts with an AE considered possibly related to AZD7762 or gem, n. AZD7762 dose (mg)/gem (mg/m2), (n) 6/750 (n=6) 6/1,000 (n=1) 6/1,000 (n=2) 9/1,000(n=3) 14/1,000 (n=6) 21/1,000(n=3) 30/1,000(n=7) 32/1,000(n=6) 40/1,000(n=8) Any grade AZD7762 causality 2 1 0 2 1 0 5 2 5 Gem causality 6 1 1 2 3 2 5 4 6 Grade ≥3 AZD7762 causality 1 1 0 0 1 0 3 0 4 Gem causality 4 1 1 1 0 1 3 1 4 SAE AZD7762 causality 0 0 0 0 0 0 1 0 2 Gem causality 0 0 0 0 0 0 1 1 2
Phase I trial of dexamethasone (Dex), carboplatin (C) and gemcitabine (G) in untreated non-small cell lung cancer (NSCLC)
Authors: J. J. Rinehart, S. Davidson, M. Deshazo, G. Cloud, L. Busby, F. Robert
Journal: Journal of Clinical Oncology (2005)

7111 Background: Our preclinical murine studies demonstrated that administration of Dex prior to chemotherapy, decreases CG toxicity and AUC of CG in bone marrow and spleen and increases AUC of CG in tumor and CG anti-tumor effects. (Clin. Can. Res.10:1633, 2004; Can. Chemo. Pharm. 53:459, 2004) Methods: Untreated, stage 4, NSCLC patients were treated with 4 courses of C, AUC 5.5 day 1, and G 1g/m2 days 1 and 8 q21days. Patients were randomized at a 1:2:2 ratio to receive no Dex (Cohort 1), or Dex 8mg bid (Cohort 2) or 16mg bid (Cohort 3), 4 days prior to and the day of each chemotherapy treatment. Dex was given only in courses 2, 3, and 4 to allow toxicity comparisons between course 1 vs. course 2. Results: Patients accrued: 28 of 30 planned patients are accrued; 23 patients who received at least 2 courses are reported here; 5 patients received only one course due to neutropenia/death (1), hepatotoxicity (1), neurotoxicity (1), withdrew consent (1), and too early (1). Demographics: m:f, 11:12; median PS-1 (ECOG), and age-65 years. Non-hematologic toxicity was similar in cohorts and courses 1 vs.2. No Dex DLTs were observed. Hematologic toxicity: Without Dex (Cohort 1) nadirs and other hematologic toxicity parameters worsened after course 1 but improved with Dex (Cohorts 2&3). For example, the ratio of nadir counts (course2 χ course1) demonstrated improvement with Dex: AGC nadir ratios for Cohorts 1, 2, and 3 (M±SE): 0.99±02., 2.68±0.8 (p<0.03, Cohorts 1 vs. 2) and 2.94 ± 0.7 (p< 0.03, Cohorts 1 vs. 3); platelet nadir ratios for cohorts 1, 2, and 3: 0.81±0.0.2, 2.68±0.6 (p<0.04), and 2.72±0.6 (p<0.03). Other parameters, including recovery times, neutropenic days, and courses given, demonstrated similar trends when comparisons were made between courses 1 & 2 or between cohorts. Data trends also suggested that 16mg is superior to 8mg bid. Responses: Cohort 1 (n=5): 2 PR, 2 PD, 1 SD; Cohort 2 (n=8): 7 PR, 1 PD; Cohort 3 (n=10): 8 PR, 1 PD, 1 SD; Conclusions: The data support our preclinical studies and suggest that a randomized phase 2 or 3 trial should be undertaken. No significant financial relationships to disclose.
Expression of angiogenic genes in resectable non-small cell lung cancer (NSCLC)
Authors: A. Cabrera, E. Jantus Lewintre, R. Sirera, A. Honguero, M. Gil, A. Blasco, E. Sanmartin, A. Arnau, R. Guijarro, C. Camps
Journal: Journal of Clinical Oncology (2009)

e22207 Background: NSCLC is a major cause of cancer-related death worldwide. The prognosis for lung cancer patients is poor with 5-years survival rates being less than 15%. It is known that angiogenesis is an essential event for solid tumour growth. Vascular endothelial growth factor (VEGF) family of ligand and receptors (VEGFR) are described as powerful angiogenic factors. VEGF belongs to a protein family, within which Placental growth factor (PlGF) is a member, they bound to their receptors at the membrane levels, gathering a cascade of intracellular events. In this study, we examine the expression of angiogenic genes in NSCLC samples correlating the expression of these genes between them and with clinicopathological variables. Methods: We performed real-time quantitative polymerase chain reaction (RT-qPCR) to assess the expression of VEGF, PlGF, VEGFR1 and VEGFR2 in frozen lung cancer specimens from untreated NSCLC patients who had undergone surgical resection (n=21). For this purpose, RNA was extracted and RTqPCR was performed using TaqMan® probes. Relative quantification was calculated by Pfaffl formulae, using an endogenous gene for normalization. We correlate the expression of the angiogenic genes between them and with other biologic variables. Statistical analysis were done using the SPSS 13.0 software. Results: Our results show that tumor samples have higher expression of PlGF than normal tissue. The expression of PlGF and VEGF correlates with the expression of their receptors in the group of samples analyzed. The expression of VEGFR1 and VEGFR2 was also significant correlated. We found a significant correlation between the levels of expression of PlGF and the tumor size (p= 0.023, Spearman's test), whereas no relation was found between the expression of the genes and the histology or stage of disease. Conclusions: Our results reveal that, in NSCLC, PlGF mRNA is higher in tumor than in normal tissue and is positively correlated with the tumor size and with the expression of angiogenic receptors. Theses finding could indicate that PlGF have some role in lung cancer progression and may be a promising new biomarker in NSCLC, but still more investigations are necessary with a larger number of samples. Supported by Instituto de Salud Carlos III (Fondo de Investigación Sanitario Grant). No significant financial relationships to disclose.
Hypoxia gene expression signature in predicting outcome in breast cancer patients
Authors: D. S. A. Nuyten, J.-T. A. Chi, Z. Wang, L. van ’t Veer, H. G. M. Bartelink, P. O. Brown, M. J. van de Vijver
Journal: Journal of Clinical Oncology (2005)

9503 Background: Gene expression profiling (GEP) has been used to identify specific subgroups of breast carcinomas (BC) that differ with respect to clinical and pathological features, including outcome. We have previously identified an expression pattern of 70 genes, associated with a high risk of developing distant metastases. Recently, we have identified a gene expression profile associated with hypoxia by exposing epithelial cells to hypoxic conditions in vitro. We hypothesized that genes induced by hypoxia may distinguish different (biological) classes of breast cancer and have therefore studied the hypoxia gene expression signature in a series of breast carcinomas. Methods: In a series of 295 patients with stage I and II breast cancer, we have previously obtained the expression profile of 25000 genes using microarray analysis. Based on the hypoxia gene expression profile, we have identified a subgroup of BC showing a “hypoxia-like profile” and a subgroup that did not; and we have compared distant metastasis free survival (DMFS) and overall survival (OS) between those two groups. Results: The median follow up was 7.8 years. Eighty tumors showed a hypoxia-like profile; and 215 did not. Patients with a hypoxia-like profile had a 42.1% DMFS at 10 years compared to 74.0% for those that were negative for the hypoxia-like profile (log rank: p<<0,00001); these figures were 43.9% and 80.7%, respectively, for OS (p<<0,00001). In multivariate analysis including clinical, genetic and pathological factors (e.g. pTxNx-stage, angio-invasion, ER-status, age, grade, chemotherapy and the 70-genes prognosis profile) the hypoxia-like profile showed independent predictive value for DMFS and OS. By combining both signatures we were able to distinguish 3 groups (Good Profile, Poor Profile-Non-Hypoxic, Poor Profile-Hypoxic). DMFS for these groups was 85.4%, 61.7% and 36.0% and OS was 94,5%, 66.5% and 37.0% at 10 years, overall p<<0.00001 for both analyses. Conclusions: In this consecutively treated series of BC patients, the hypoxia-like profile identifies patients that differ with respect to prognosis, hypoxia-like profile tumors being associated with worse outcome. Combining different GEP may result in improved classification of BC. No significant financial relationships to disclose.
Impact of a psychosocial intervention on performance status and coping
Authors: H. K. Lyerly, T. Staley, J. E. Herndon, A. Coan, J. L. Wheeler, K. Rowe, B. Horne, A. P. Abernethy
Journal: Journal of Clinical Oncology (2009)

9611 Background: Psychosocial distress is a critical cancer comorbidity; new interventions are needed. Pathfinders, a manualized psychosocial care program, provides patient navigation, counseling, coping skills training, mind/body techniques, and lifestyle advice. Methods: This prospective, single-arm, pilot study enrolled adult metastatic breast cancer patients with prognosis ≥6 months. Consenting participants met with a Pathfinder (trained social worker) at least monthly, with interim phone/email contact. Pathfinders worked with patients to identify inner strengths, teach coping skills, engage complementary/alternative providers, employ mind/body techniques, and support healthy lifestyle. At baseline, month 3 and month 6, patients completed surveys including Patient Care Monitor (PCM; a review of systems with 6 subscales and a global quality of life [QOL] score), and Functional Assessment of Chronic Illness Therapy - Fatigue subscale (FACIT-F). Results: Participants (n=50) were: mean age 51.2 years (SD 11.5); 24% non-white; 74% married; 50% did not complete college; the cohort had advanced cancer and short prognosis with 6-month attrition from death, 18%. Scores on the PCM Distress subscale improved from baseline to 3 months with a mean change of -3.42 (n=36; p=0.008) and from baseline to 6 months of -4.11 (n=28; p=0.002). PCM Despair subscale scores also improved: mean change of -4.53 (p=0.006) and -6.93 (p=0.016), respectively. PCM QOL and FACIT-F scores improved from baseline to 3 months; however, the change at 6 months, with smaller sample, was not statistically significant. Mean change in QOL from baseline to 3 and 6 months was 2.88 (n=30; p=0.006) and 2.66 (n=25; p=0.079), respectively. Mean change in FACIT-F from baseline to 3 and 6 months was 2.91 (n=39; p=0.020) and 1.29 (n=32; p=0.407), respectively. Conclusions: Pathfinders had significant positive effect on key psychosocial and QOL outcomes, notably distress and despair, for cancer patients despite advanced disease and worsening symptoms. No significant financial relationships to disclose.
Allocation of high demand, scarce medical technology: Lessons for proton radiotherapy
Authors: K. Rakszawski, J. E. Bekelman
Journal: Journal of Clinical Oncology (2009)

e17570 Background: Proton radiotherapy is a scarce therapeutic resource. To inform policy development on the allocation of proton radiotherapy, we performed a systematic review to investigate the use of high demand, scarce medical technology in three settings: 1) proton radiotherapy; 2) liver transplantation; and 3) intensive care units (ICUs). Methods: Studies were identified by searching MEDLINE (from 1990 to 2008) and references of articles, letters, commentaries, and editorials. We included English-language quantitative and qualitative studies, commentaries and policy papers addressing the methods and effects of resource allocation. A total of 2,304 citations were screened, 197 potentially eligible full articles were retrieved on a basis of abstract review, and 34 studies met our inclusion criteria (1 related to proton radiotherapy, 10 related to liver transplantation, and 23 related to ICUs). Data was extracted from each of the 34 studies into tabular displays, drawing from the balance sheet model for integrating and interpreting multiple types of evidence. Results: A single case report addressed the allocation of proton radiotherapy. Within the liver transplantation setting, the Model for End-Stage Liver Disease (MELD) system utilizes a priority scale based on objective indicators of disease severity. One study showed that use of the MELD system increased transplants among patients with greater disease severity and reduced transplant wait times. Within the ICU system, formal admission guidelines have been developed by committees with input from multiple stakeholders. However, one survey showed that while the majority of hospitals have formal guidelines, only 25% use these guidelines in routine clinical practice. Conclusions: Evidence to inform policy development on the allocation of proton radiotherapy is sparse. The substantial potential benefits and costs of proton radiotherapy underscore the need for an objective, transparent system for proton radiotherapy allocation. [Table: see text]
Abstract 41: Explant-Derived Cells from Chronic Heart Failure Activated Endothelial-Mesenchymal Transition and Attenuated Pluripotency Genes Expression
Authors: Liudmila Zakharova, Hikmet Nural, Mohamed A Gaballa
Journal: Circulation Research (2012)

Cardiac progenitor cells are generated from atria explants; however the cellular origin and the mechanisms of cell outgrowth are unclear. Using transgenic tamoxifen-induced Willms tumor 1 (Wt1)-Cre/ERT and Cre-activated GFP reporter mice, we found approximately 40% of explant-derived cells and 74% of explant-derived c-Kit+ cells originated from the epicardium. In atria from sham hearts, Wt1+ cells were located in a thin epicardial layer, while c-Kit+ cells were primarily found within both the sub-epicardium and the myocardium, albeit at low frequency. No overlap between c-Kit+ and Wt1+ cells was observed, suggesting that epicardial Wt1+ cells do not express c-Kit marker in vivo, but more likely the c-Kit marker was acquired in culture. Compared with 4 days in culture, at day 21 we observed 7 folds increase in Snail gene expression; 32% increase in α-smooth muscle actin (SMA) marker, and 30% decrease in E-cadherin marker, suggesting that the explant-derived cells underwent epithelial to mesenchymal transition (EMT) in vitro. Cell outgrowths released TGF-β (1036.4 ± 1.18 pm/ml) and exhibited active TGF-β signaling, which might triggered the EMT. Compared to shams, CHF cell outgrowths exhibited elevated levels of EMT markers, SMA (49% vs. 34%) and Snail (2 folds), and reduced level of Wt1 (11% vs. 22%). In addition, CHF cell outgrowths had two folds increase in Pai1 gene expression, a direct target of TGF-β signaling. In c-Kit+ cells derived from CHF explants, Nanog gene expression was 4 folds lower and Sox 2 was 2 folds lower compared with cells from shams. Suppression of EMT in cell outgrowth increased the percentage of c-Kit+ and Wt1+ cells by 17%, and 15%, respectively. Also suppression of EMT in c-Kit+ cells resulted in 4 folds increase in Nanog and 3 fold increase in Sox2 gene expressions. Our results showed that CHF may further exuberates EMT while diminishes the re-activation of pluripotency genes. Thus, EMT modulation in CHF is a possible strategy to regulate both the yield and the pluripotency of cardiac-explant-derived progenitor cells.
An Arg/Ser Substitution in the Second Epidermal Growth Factor–Like Module of Factor IX Introduces an O-Linked Carbohydrate and Markedly Impairs Activation by Factor XIa and Factor VIIa/Tissue Factor and Catalytic Efficiency of Factor IXa
Authors: Mark S. Hertzberg, Sandra L. Facey, Philip J. Hogg
Journal: Blood (1999)