tbuckley/cabot-search huggingface dataset:
Communication of the essential elements of informed consent (IC) for research: A RIAS analysis of phase I clinical trial encounters.
Authors: C. Daugherty, F. J. Hlubocky, N. E. Kass, D. Roter, S. Larson, J. Sugarman, K. Wroblewski, M. J. Ratain
Journal: Journal of Clinical Oncology (2010)

6045 Background: Advanced cancer patients (ACP) in phase I clinical trials are unable to recall many important elements of IC, yet the content of discussion between physician-investigators (PI) and ACP consenting to such trials has not been well described. Methods: Clinical encounters were recorded between 131 ACP entering phase I trials and 25 PIs at three institutions (University of Chicago; Johns Hopkins; and Duke University). ACP completed follow-up questionnaires 1 week later to assess understanding of IC elements, e.g., research purpose of phase I trials. Recordings were analyzed using the Roter Interaction Analysis System (RIAS), and coding for terms associated with IC elements. Results: To date, 87 ACP-PI encounters have been analyzed. Average length of encounters: 30.4 min (range: 5.7-77.8 min). ACP demographics include: median age 60y (33-83); 55% female; 88% Ca; 55% < $60,000. PIs were coded as stating: 1) The purpose of a phase I trial as determining dosage/toxicity in 40% of encounters; 2) Physical risk of a trial in 70% of the encounters; 3) Life-threatening risks in 10% of the encounters; 4) Potential benefits gained by subject participation in the trial related to improvement in quality of life or stabilization of disease in 63% of encounters; and 5) Trial alternatives in 58% of the encounters. Within follow-up interviews, 26% of ACP described the purpose of a phase I trial as determining drug safety; 67% described alternatives to trial participation. An association existedbetween coding for PI statements re: the purpose of a phase I trial as dosage/toxicity and ACP correctly recalling the purpose of the trial (86% vs. 14%, p < 0.05). Conclusions: PI communication and subsequent ACP understanding of important elements of IC remain inadequate in the phase I trial setting. No significant financial relationships to disclose.
Transformation and Neoplastic Development of Hamster Chondrocytes After Exposure to 4-Nitroquinoline-1-oxide and 3-Methylcholanthrene in Tissue Culture2
Authors: Yoichi Katoh
Journal: JNCI Journal of the National Cancer Institute (1977)

Sternal hyaline cartilages of Syrian hamsters were dissociated with collagenase and culured. Primary monolayer cultures of the dissociated cells were morphologically homogeneous. Secondary cultures of the chondrocytes were treated with 1 x 10(-6) or 2 x 10(-6) M 4-nitroquinoline-1-oxide (4NQO) for 3 hours or with 5 or 10 microgram 3-methylcholanthrene (MCA)/ml for 3 days. Cultured chondrocytes transformed morphologically 29-51 days after 4NQO treatment and 41-61 days after MCA treatment and began to grow continuously in vitro. Cultures of transformed cells, like transformed fibroblasts. Untreated cells and cells treated with dimethyl sulfoxide did not transform within at least 110 days after inoculation. Among the transformed cells, one near-diploid cell line preserved the distinct phenotypic expression of chondrocytes, whereas heteroploid cell lines lost their differentiated features. The near-diploid cell line produced nodules in the cheek pouches of hamsters within a week, by the nodules regressed later. They showed the chondrogenic properties of the original cells and stained metachromatically with toluidine blue. Heteroploid cell lines formed progressive tumors with few chondrogenic features; these tumors were diagnosed as fibrosarcomas.
Improvement of leukemia-free survival (LFS) and reduction of relapse incidence by allogeneic stem cell transplantation (SCT) in elderly patients (pts) with AML irrespective of the FLT3-ITD and npm status except npm+/flt3(ITD)-.
Authors: D. Niederwieser, F. Schueler, U. Hegenbart, G. Maschmeyer, T. Fischer, C. Junghanss, H. Wolf, H. G. Sayer, U. Kreibich, G. Doelken
Journal: Journal of Clinical Oncology (2010)

6505 Background: Acquired mutations of the flt3 and npm1 genes have been shown to determine outcome in younger pts with AML. Here, the influence of flt3 and npm1 mutations on outcome of elderly pts (> 60 a) was analyzed in relation to either chemotherapy (CT) or SCT. Methods: Of the 498 pts entered into the curative arm of the #69 study for pts > 60 a, 357 are evaluable and 158 of these had flt3 and npm1 available as of Oct 2009. Complete remission was obtained in 191 of the 357 pts after induction chemotherapy. Flt3 and npm1 was available in 53 of 81 and 44 of 59 pts in CR1 receiving either a second consolidation or allogeneic SCT. Consolidation consisted of CT or, in pts with related or unrelated donors, of SCT after 200 cGy TBI. Results: Overall survival (OS) of the 158 pts with known npm1 and flt3(ITD) status was 33 ± 3% at 2a. Mutation status did not significantly influence OS, but did influence the EFS of pts in CR1 after induction (27 ± 11% vs. 51 ± 7% for flt3(ITD)+ vs. flt3(ITD)- p < 0.01; 69 ± 9% vs. 34 ± 7% for npm1+flt3- vs. non-npm1+flt3- p = 0.01). Subsequently the effect of CT and SCT on EFS was investigated according to the flt3 and npm1 status. Pts with wild type flt3 and with npm1+/flt3- had better EFS than the rest. However, SCT compared to CT increased EFS irrespective of the flt3-ITD status (EFS 59 ± 9% vs. 43 ± 9% for flt3(ITD)- and 40 ± 15% vs. 15 ± 13% at 2 a for flt3(ITD)+ after SCT and CT respectively; p = 0.036) by reducing the relapse incidence (31 ± 9% vs. 56 ± 9% for flt3(ITD)- and 52 ± 16% vs. 85% ± 13% at 2 a for flt3(ITD)+ after SCT and CT respectively; p = 0.012). Except for npm1+/flt3(ITD)- pts, SCT was also superior to CT (EFS 62 ± 16% vs. 74 ± 11% for npm1+/flt3- and 51.2 ± 9.4 vs. 11.9 ± 7.7% for all others after SCT and CT respectively; p < 0.01). Conclusions: In conclusion, flt3 and npm1 status does not influence OS of AML pts > 60 a. However, EFS of pts in CR1 is highly dependent upon mutation status and, except in npm1+/flt3(ITD)- pts, increased by SCT rather than CT by reducing relapse incidence. No significant financial relationships to disclose.
P2-138: Disruption of a conserved ion pair E884-R958 in EGFR differentially alters kinase inhibitor sensitivity and downstream signaling
Authors: Zhe Tang, Shan Jiang, Runlei Du, Sascha Dietrich, Edward T. Petri, Titus J. Boggon, Balazs Halmos, Jeffrey A. Kern, Patrick C. Ma
Journal: Journal of Thoracic Oncology (2007)
Generation of aggregation prone N-terminally truncated amyloid β peptides by meprin β depends on the sequence specificity at the cleavage site
Authors: Caroline Schönherr, Jessica Bien, Simone Isbert, Rielana Wichert, Johannes Prox, Hermann Altmeppen, Sathish Kumar, Jochen Walter, Stefan F. Lichtenthaler, Sascha Weggen, Markus Glatzel, Christoph Becker-Pauly, Claus U. Pietrzik
Journal: Molecular Neurodegeneration (2016)

The metalloprotease meprin β cleaves the Alzheimer's Disease (AD) relevant amyloid precursor protein (APP) as a β-secretase reminiscent of BACE-1, however, predominantly generating N-terminally truncated Aβ2-x variants. Herein, we observed increased endogenous sAPPα levels in the brains of meprin β knock-out (ko) mice compared to wild-type controls. We further analyzed the cellular interaction of APP and meprin β and found that cleavage of APP by meprin β occurs prior to endocytosis. The N-terminally truncated Aβ2-40 variant shows increased aggregation propensity compared to Aβ1-40 and acts even as a seed for Aβ1-40 aggregation. Additionally, we observed that different APP mutants affect the catalytic properties of meprin β and that, interestingly, meprin β is unable to generate N-terminally truncated Aβ peptides from Swedish mutant APP (APPswe). Concluding, we propose that meprin β may be involved in the generation of N-terminally truncated Aβ2-x peptides of APP, but acts independently from BACE-1.
Abstract 17862: Radiation Dose and Downstream Testing from Coronary CT Angiography (CTA) versus SPECT Myocardial Perfusion Imaging (MPI) for the Evaluation of Chest Pain in the Emergency Department (ED)
Authors: William L Duvall, John Savino, Elliot Levine, Patrick Looser, Judah Rauch, Lori B Croft, Andrew J Einstein, Milena J Henzlova
Journal: Circulation (2012)

Background: While recent CTA studies have suggested lower radiation dose and faster study time than MPI, this comparison has been to older Na-I SPECT cameras using traditional rest-stress protocols...
A retrospective review of prostate specific antigen doubling time (PSA-DT) in men with hormone refractory prostate cancer (HRPC)
Authors: R. C. Semeniuk, P. M. Venner, J. Hanson, S. A. North
Journal: Journal of Clinical Oncology (2005)

4666 Background: Men with metastatic HRPC form a heterogeneous population consisting of men who are asymptomatic to those who have significant pain. Survival may range from a few months to several years. Therefore, patient selection is critical in determining which patients may receive the most benefit from aggressive chemotherapy. PSA-DT has been shown to be a surrogate for survival in earlier stages of prostate cancer but its usefulness as a predictor for survival in HRPC has not been resolved. Methods: A retrospective chart review of 225 patients with HRPC referred to the Cross Cancer Institute in Edmonton, Alberta, Canada from 1998–2002 was undertaken. Eligible patients had three sequential rises in PSA despite having castrate levels of serum testosterone and metastatic disease detected by either a bone or CT scan. The PSA-DT at the time of diagnosis of HRPC was calculated using a standard formula. Additional variables examined included: Gleason score, initial treatment, treatment for HRPC, hemoglobin and serum LDH. Optimal PSADT stratification was obtained by selecting the most significant p-value using the log-rank χ2 statistic. Kaplan-Meier curves were used to estimate overall survival and differences were evaluated using the log-rank test. Results: Median age at diagnosis of HRPC was 70.0 years. During the follow-up period 80% of patients died; 93% were prostate cancer specific deaths. In the overall group, median survival from diagnosis of HRPC was 15.1 months (range 0.5–90.5). Using χ2 tests, optimal PSA-DT stratification for survival was found to be 70 days. Patients with a PSA-DT of ≤70 days survived 11 months compared to 19 months for a PSA-DT of >70 days (RR 1.79, p<0.0001). Conclusions: PSA-DT serves as an independent prognostic marker for survival in patients with metastatic HRPC. Men with a PSA-DT of <70 days have a significantly shorter survival compared to men with a PSA-DT >70 days. Clinical trials in HRPC need to stratify treatment arms for PSA-DT. Including PSA-DT with other clinical data could help clinicians select men at high risk for early mortality who may consider aggressive treatment regimens, such as docetaxel based treatment, even if asymptomatic. No significant financial relationships to disclose.
Glassy cell carcinoma of the uterine cervix
Authors: A. Restivo, P. Disilvestro, R. Moore, S. Weitzen, S. Kaufman, Y. Puthawala, C. Granai, M. Gordinier
Journal: Journal of Clinical Oncology (2006)

15050 Background: Glassy Cell Carcinoma of the uterine cervix is a rare, aggressive form of cervical cancer accounting for only 1–5% of all cervical carcinomas. To date, there is no consensus on treatment modalities, but most advocate for a more aggressive treatment strategy including both radical surgery and radiation therapy. The objective of this study was to analyze the clinical features, treatment, and outcome of patients with Glassy cell carcinoma diagnosed at our institution. We hypothesized that such aggressive therapies yield survival benefits which approximate those of the more common squamous cell carcinomas of the cervix. Methods: In collaboration with the Department of Radiation Oncology at Rhode Island Hospital, a retrospective comprehensive chart review of all patients diagnosed with Glassy cell carcinoma of the cervix between the years 1993 and 2005 was undertaken at Women and Infant’s Hospital, Providence, RI. All cases were assessed for clinicopathologic features, treatment strategies, and outcome, including progression free survival and overall survival rates. Results: Twenty-eight patients with biopsy proven Glassy Cell Carcinoma of the cervix were identified. Eleven (39%) were less than age 40, and five (18%) were less than age 30. Of these, 19 were either stage IB or IIA, and 15/19 (79%) received multimodality therapy, a combination of radiation, chemotherapy, and surgery, as initial treatment. When survival was broken down by mode of treatment, 25% of patients who received single modality treatment (either surgery or radiation) were DF at two and five years. In contrast, those patients who were treated with bimodal therapy had a DFS of 93% at 2 years and 84% at 5 years. Thus the survival of patients with glassy cell histology treated at our institution with multimodality therapy approximates the survival of similar stage patients with squamous and adenocarcinoma, with a mean follow-up of greater than 5 years. This represents a distinct improvement when compared to national survival statistics. Conclusions: The favorable survival results of this aggressively treated population, supports the belief that multimodality therapy is preferable in patients with glassy cell carcinoma of the cervix even in early stage disease. However, optimal treatment regimens have yet to be determined and is a field for further study. No significant financial relationships to disclose.
Prognostic significance of x-linked inhibitor of apoptosis protein expression in renal cell carcinoma
Authors: Y. Mizutani, H. Nakanishi, T. Shiraishi, T. Nakamura, K. Mikami, N. Takaha, K. Okihara, O. Ukimura, A. Kawauchi, T. Miki
Journal: Journal of Clinical Oncology (2008)

5105 Background: X-linked inhibitor of apoptosis protein ( XIAP ) is one of the IAP family members which block apoptosis through inhibition of caspase 3 and 9. However, little is known about the clinical significance of XIAP in a variety of cancers including renal cell carcinoma ( RCC ). The current study investigated XIAP expression in 120 normal kidneys and RCCs and examined its prognostic significance. Methods: The level of XIAP expression was determined by Western blot analysis using 120 non-fixed fresh frozen tissues of RCCs and normal kidneys. Cytotoxicity was examined by the MTT assay. Results: The mean level of XIAP expression was 1.6-fold higher in RCC compared to autologous normal kidney. In Stage I/II RCC, the mean XIAP expression level was almost identical to that in normal kidney, whereas XIAP expression in Stage III/IV RCC was 2.5-fold higher. The level of XIAP expression positively correlated with the grade of RCC. Patients with RCC with low XIAP expression had a longer postoperative disease-specific survival than those with high expression in the 5-year follow-up. Treatment of RCC cells with XIAP antisense oligonucleotide enhanced tumor necrosis factor ( TNF )-α- mediated, Fas-mediated and TNF-related apoptosis-inducing ligand ( TRAIL )-mediated apoptosis. Conclusions: The present study has demonstrated that XIAP expression was up-regulated in RCC, and that high XIAP expression in RCC predicted worse prognosis. In addition, XIAP antisense oligonucleotide sensitized RCC to TNF-α-induced, Fas-induced and TRAIL-induced apoptosis. These findings suggest that XIAP expression in RCC may be used as a prognostic parameter, and that down-regulation of XIAP expression in RCC may potentiate immunotherapy. No significant financial relationships to disclose.
Detection of BRAF and KRAS mutations in DNA released by tumors in peripheral blood by an advanced digital droplet PCR.
Authors: Giorgia Marisi, Marzia Del Re, Marco Giorgio Bianchi, Antonia Martinetti, Carlotta Antoniotti, Paola Ulivi, Riccardo Marconcini, Filippo Pietrantonio, Marta Schirripa, Elisa Sottotetti, Fotios Loupakis, Anna Tesei, Wainer Zoli, Filippo G. De Braud, Dino Amadori, Alfredo Falcone, Romano Danesi
Journal: Journal of Clinical Oncology (2013)

e22056 Background: Cell-free tumor DNA (cftDNA) is released into the circulation and its recovery from plasma is a non-invasive alternative to tumor biopsy for applications related to molecular profiling. A potential use in therapeutic interventions is the periodic monitoring of cftDNA for the identification of molecular changes associated with resistance to target-specific treatments or when the mutational status in tumor tissue is not available. Methods: Samples (6 ml) of peripheral blood were drawn from patients with colorectal (CRC, n= 19) and thyroid (n= 1) cancers and melanoma (n= 8). CRC tumors were KRAS wild-type (n= 3) or carried the BRAF V600E (n= 6), KRAS G12D (n= 9) and G12V (n= 4) mutations. All melanomas and the thyroid cancer carried the BRAF V600E mutation. DNA was extracted from plasma with QIAamp Circulating Nucleic Acid Kit to recover DNA fragments of ≤1000 bp. PCR amplification was carried out with a QX100 ddPCR System (Bio-Rad) on 20 μL-samples containing cftDNA and TaqMan probes for BRAF V600E (1799T&gt;A), KRAS G12D (35G&gt;A) and G12V (35G&gt;T) labeled with FAM/VIC. Samples were then loaded into a droplet reader, which discriminates the difference in fluorescence amplitudes on the basis of target gene amplification. Results: The concordance between mutations in tumors (T) and plasma (P) for BRAF V600E was: melanomas 8 T vs. 6 P; thyroid cancer 1 T vs. 0 P; CRC 6 T vs 3 P. Concerning KRAS in CRC the results were: G12D 9 T vs. 7 P, G12V 4 T vs. 0 P. Overall, the percentage of concordant samples were: V600E 60%, G12D 77,8%, G12V 0%. Interestingly, in 2 patients with wild-type KRAS tumor, the G12D and G12V mutations were found in plasma. Conclusions: ddPCR is a third-generation PCR technique for highly sensitive detection of DNA fragments. Detection of mutations in cftDNA by advanced technological platforms has important applications in the monitoring of patients for the occurrence of secondary mutations, amplifications and expansion of cell clones that render their tumors resistant to target-specific anticancer agents, unraveling the resistant phenotype before the clinical progression of the disease. Acknowledgments: this study was funded in part by MIUR/PRIN 2011-2012 (Rome, Italy).
A multicenter cohort to compare quality of life in breast cancer patients according to sentinel lymph node biopsy (SNLB) or full axillary clearance (AC)
Authors: T. S. Dabakuyo, J. Fraisse, S. Causeret, S. Gouy, M. Padeano, C. Loustalot, J. Cuisenier, J. Sauzedde, S. Boulet, F. Bonnetain
Journal: Journal of Clinical Oncology (2008)

9633 Background: This prospective study assessed and compared the impact of surgical technique modalities of breast cancer patients on quality of life (QoL). Methods: A pragmatic prospective multicentric study was opened in five hospitals of the Cote d’Or and Saone et Loire (French provinces). All women undergoing breast surgery as primary treatment were eligible. The EORTC QLQ- C30 and the EORTC QLQ BR 23 questionnaires were used to assess the global health status (GHS), the arm (BRAS) and breast (BRBS) symptoms scales. The QoL was measured before surgery, just after surgery and six and twelve months afterwards. The Kruskal Wallis test was used to compare scores according to the surgical procedure using the Bonferroni correction for multiple contrast comparisons. The Wilcoxon matched-pairs signed rank test was used to compare scores according to the time of measurement. A mixed model analysis of variance for repeated measurements was applied to assess the longitudinal effect of surgical techniques on QoL. Results: Between January 1st 2005 and January 1st 2006, 518 breast cancer patients were included. Two hundred thirty-five underwent AC, 222 patients SNLB, and 61 patients had SLNB with complementary axillary lymph node dissection. Before surgery, GHS (p=0.7807), BRAS (p=0.7688) and BRBS (p=0.3007) QoL scores were similar whatever the surgical procedure. As compared to other surgical groups, GHS 75.91(SD=17.44) and BRAS 11.39 (SD=15.36) were better in the SNLB group 12 months after surgery. Whatever surgery type, GHS decreased after surgery (p<0.0001), but increased 6 months later (p=0.0016). BRAS symptoms increased just after surgery (p=0.0329) and until 6 months (p<0.0001) before decreasing (p<0.0001). Whatever the follow up, GHS and BRAS were better in the SNLB group than in the SNLB+ classical axillary dissection group. Mean differences were respectively 4.94 (p = 0.0185) and 6.28 (p = 0.0013). Conclusions: SNLB seems to improve QoL in breast cancer patients. However, surgeons must be cautious, SNLB with complementary axillary lymph node dissection results in a poorer QoL. No significant financial relationships to disclose.
The prognostic significance of the ratio of positive to total nodes in colorectal cancer
Authors: M. Ng, S. Roy-Chowdhury, S. S. Lum, J. W. Morgan, J. H. Wong
Journal: Journal of Clinical Oncology (2008)

4045 Background: Patients with node positive colorectal cancer (CRC) have a grave prognosis. Current AJCC staging distinguishes between those with 1–3 positive lymph nodes (N1) and those with 4 or more (N2). We sought to determine whether the ratio of positive to total nodes examined (LNR) was a more powerful predictor of outcome than N staging. Methods: 2,636 patients diagnosed between January 1, 1994 to December 31, 2003 with stage III CRC from Region 5 of the California Cancer Registry were analyzed. LNR was stratified into quintiles of <0.19, 0.2–0.39, 0.4–0.59, 0.6–0.70 or 0.8–1.0. The major endpoint was actuarial 5-year disease specific survival (DSS). Significant differences in DSS between groups were determined by the log-rank test. A multivariate Cox proportional hazard regression was performed for all patients to determine whether N stage, LNR, number of lymph nodes examined, or number of positive lymph nodes were independent prognostic factors. Results: The median age was 71 with women making up 49.9% of the patients. 65% of the patients (n=1,717) had N1 disease; and 35% had N2 disease (n=919). 5 year DSS among N1 and N2 disease was 65% and 47%, respectively (p<0.0001). Within the N1 group, increasing LNR quintiles had worsening 5 year DSS of 71%, 63%, 59%, 52% and 50% (p<0.0001). Similarly for the N2 group, 5 year DSS worsened with increasing LNR quintiles: 74%, 53%, 52%, 43%, and 31% (p<0.0001). Absolute difference in DSS between the highest and lowest quintiles for N1 was 21%; and N2, 43%. Multivariate analysis revealed that the number of nodes examined (p=0.0116), number of positive lymph nodes (p=0.0002), N stage (p=0.0139) and LNR (p=0.017) were all predictors of DSS. Quintiles 4 (RR=1.39, 95% CI=1.0087–1.9253) and 5 (RR=1.72, 95% CI=1.2406–2.4004) were more powerful predictors of DSS than N stage (RR=1.2613, 95% CI=1.0478–1.5184) or number of positive lymph nodes (RR=1.0457, 95% CI=1.0223–1.0698). Conclusions: LNR along with number of lymph nodes examined and number of positive lymph nodes is a predictor of DSS in stage III patients. Furthermore, a LNR ≥ 0.6 (quintiles 4 and 5) is a stronger prognosticator than N stage or number of positive lymph nodes. No significant financial relationships to disclose.
Effects of Intramuscular Epinephrine on Cardiovascular Parameters during IgE-Mediated Allergic Reactions to Peanut
Authors: Monica Ruiz-Garcia, Carl Hayward, Alistair Tang, Andrew Clark, Isabel J. Skypala, Stephen R. Durham, Alexander R. Lyon, Robert J. Boyle, Paul J. Turner
Journal: Journal of Allergy and Clinical Immunology (2016)