tbuckley/cabot-search huggingface dataset:
Effect of Providing Cancer Patients With the Audiotaped Initial Consultation on Satisfaction, Recall, and Quality of Life: A Randomized, Double-Blind Study
Authors: L.M.L. Ong, M.R.M. Visser, F.B. Lammes, J. van der Velden, B.C. Kuenen, J.C.J.M. de Haes
Journal: Journal of Clinical Oncology (2000)

PURPOSE: By means of a randomized double-blind study, the effect of providing taped initial consultations on cancer patients’ satisfaction, recall, and quality of life was investigated. PATIENTS AND METHODS: Consecutive cancer patients referred to either the gynecology or medical oncology outpatient clinic were eligible. Initial consultations were audiotaped. Patients were either provided with the tape (experimental group) or not (control group). Baseline variables included sociodemographics, preferences for information, coping styles, and clinical characteristics. Follow-up (after 1 week and 3 months) variables included attitudes toward the intervention, satisfaction, recall, and quality of life. Assessments took place through mailed questionnaires and telephone interviews. RESULTS: Two hundred one patients were included (response, 71%), 105 in the experimental group and 96 in the control group. Most patients (75%) listened to the tape, the majority of which (73%) listened with others. Almost all patients, both in the experimental group (96%) and control group (98%) were positive about the intervention. Expectations were confirmed; patients provided with the tape were more satisfied (P &lt; .05) and recalled more information (P &lt; .01) than patients without the tape. The intervention did not have an effect on quality of life. An interaction effect was found between the intervention and patients’ age on satisfaction with the taped consultation (P &lt; .01) and recall of diagnostic information (P &lt; .01); access to tapes seems more helpful in enhancing satisfaction in younger patients and recall of diagnostic information in older patients. CONCLUSION: Cancer patients and their families value the taped initial consultation. This intervention enhances their satisfaction and improves their recall of information. Tapes seem more helpful in enhancing satisfaction in younger patients and recall of diagnostic information in older patients.
DNA methylation profile predicts survival of patients with resected malignant pleural mesothelioma (MPM)
Authors: G. L. Ceresoli, A. Destro, E. Baryshnikova, I. Garassino, P. A. Zucali, E. Morenghi, A. Testori, M. Alloisio, M. Roncalli, A. Santoro
Journal: Journal of Clinical Oncology (2007)

7712 Background: Methylation in different tumor suppressor genes is among the most frequent alterations reported in MPM patients (pts). DNA methylation increases upon immortalization and transformation of human mesothelial cells, and demethylating agents were found to have some activity in MPM. In this study we analysed the methylation status of the promoter region of four candidate genes in MPM: p15INK4B INK4B , p16INK4A INK4A , RASSF1A and NORE1A. Methods: Samples of 79 consecutive MPM pts who underwent surgical procedures (41 extrapleural pneumonectomy (EPP), 32 partial pleurectomy, 6 diagnostic biopsy) at our Institution from 1997 to 2005 were analyzed. DNA was isolated from each paraffin-embedded MPM; the methylation status of the four genes was evaluated by a methylation-specific PCR method (MSP). Correlations between methylation status, clinico-pathological parameters (including proliferation index) and overall survival (OS) were examined in all pts and in the EPP subgroup. Proliferation index was evaluated as percentage of nuclear immunoreactivity/10 high-power field using a mouse monoclonal antibody anti-human Ki-67, clone MIB-1 (DAKO Corporation, Carpinteria, CA). Results: The MSP analysis documented gene promoter methylation in at least one gene in 30 cases (38%). The methylation frequency of each gene was: p15INK4B 15 cases (19%), p16 INK4A 9 (11.4%), RASSF1A 16 (20.2%), Nore1A 4 (5.1%). Of the 30 methylated MPMs, 18 (60%) showed only one methylated gene, 10 (33.3%) were methylated in two genes and 2 (6.7%) in three. Methylation in at least one gene was associated to a higher proliferation index (P=0.058, ANOVA), but not to OS, in the whole study population. In pts treated with EPP, the 22 methylated cases showed a trend to a worst OS in comparison to 19 unmethylated cases (median OS 16 months vs 35 months, P=0.066, HR=2.01, 95% CI 0.94–4.30, Cox regression), independently by histology and nodal status. Conclusions: In pts treated with EPP, the methylation profile of p15INK4B INK4B , p16INK4A INK4A , RASSF1A and NORE1A appeared to be an independent prognostic factor for OS. The methylation status was correlated to proliferation rate, indicating a potential role of these oncosuppressor genes in the neoplastic progression of MPM. No significant financial relationships to disclose.
22 year phase 1/2 study of single agent carboplatin in metastatic seminoma: Potential for acceleration by a new surrogate end point, 72 hr PET scan response?
Authors: R. Oliver, T. Powles, P. Ell, U. Somasundram, J. Shamash
Journal: Journal of Clinical Oncology (2006)

14565 Background: That metastatic seminoma may be more chemo-curable than non-seminoma was first suggested by Samuels (1980 Proc ASCO 21 abst 415) 4 of 5 patients durable CR to single agent cisplatin and by Oliver (1984 Proc ASCO 3. Abst 636) 9 of 10 durable responses. Carboplatin proved less effective and in randomised trials involving 361 patients relapse free survival was 72% with Carbo and 92% with cisplatin-based combination. Prompted by successful dose escalation of carboplatin in ovarian cancer, the initial phase 1 study that preceded the UK randomised trial was reopened and dosage escalated to AUC 8 and then 10. This abstract updates this study and provides more prolonged follow up of the previous reported cases. Methods: Initially patients received Carboplatin 450 mg/m 2 (1983–7) and then AUC 7 (88–94), 8 (95–6) and 10 (97–06). The treatment was repeated q21 when possible and if delayed because of toxicity blood counts were repeated every 24 hours. Results: 60 metastatic seminoma patients have been treated between 1983 and 2006. 79%/95% of 19 receiving 450 mg/m 2 , 88%/94% of 17 receiving AUC 7 or 8 and 92%/100% of 24 receiving AUC 10 are progression free/alive. Overall 58 (97%) are alive and with 28 patients followed more than 10 years there have been no relapses after 26 months. Mild and rapidly recovering (med 14 d) transaminitis in 64% of AUC × 10 (med 93 range 51–541) suggests this may be the upper limit for safe use. As a pilot study 5 seminomas receiving AUC × 10 and 6 non-seminomas receiving BEP had PET scan before and at 72 hours after treatment. The only patient failing to respond substantially was a seminoma who showed increased PET activity on AUC × 10 but achieved complete remission of PET activity after one course of BEP. Conclusion: This data confirms the need for more studies of single agent platinum analogues in seminomas and reinforces the view that it may be preferable to radiotherapy for patients electing adjuvant treatment. With increasing attention being paid to late events, minimizing treatment toxicity and finding a fast track approach to proving safety is an increasing need. The data presented demonstrates the potential of early PET scan as a surrogate for response and could have accelerated the phase 1/2 study reported. No significant financial relationships to disclose.
The interaction of HMGA2 with Ku80/70 dysregulates DNA-PK signaling: a novel regulatory pathway in response to genotoxic stress by doxorubicin
Authors: Lee Ming Boo, Angela Li, Xu Li, Helen Lin, Benjamin Chen, David Chen, Yun Yen, David Ann
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

1972 

Ku80/70 heterodimers promote nonhomologous end joining (NHEJ) of DNA breaks by complexing with DNA-PKcs and, as shown here, interact with architectural transcription factor HMGA2. Consequently, the interaction of HMGA2 with Ku80/70 leads to accumulation of basal DNA strand breakage and dysregulation of DNA-PK signaling upon exposure of doxorubicin (Dox). We have previously reported the hypersensitivity of HMGA2-expressing cells to Dox, cisplatin and irradiation; however, the detailed mechanism underlying HMGA2-dysregulated DNA damage response remains unclear. In the present study, we first demonstrate that HMGA2-expessing cells display a deficiency in overall and precise end-joining repair and accumulate more endogenous DNA damage prior to Dox-treatment. Second, HMGA2 renders a sustained phosphorylation of DNA-PKcs-Ser-2056/-Thr-2609, perhaps reflecting the lack of proper repair in Dox-treated cells. While HMGA2 potentiates Dox-induced caspase-3 activation and accumulation of p53-Ser-15 phosphorylation, HMGA2 attenuates phosphorylation of ATM-Ser-1981 and Chk2-Thr-86 in response to Dox-exposure. Altogether, DNA-PK signaling and DNA repair are probably uncoupled in HMGA2-expressing cells. Biochemically, both C-terminal region and AT-hooks of HMGA2 are indispensable for the interaction of HMGA2 with Ku80 and the enhancement of Dox-elicited cytotoxicity. Therefore, HMGA2 dysregulates DNA damage-triggered DNA-PK and ATM signaling network, representing a novel regulatory pathway to promote sensitivity to DNA damage.
First human dose escalation study in patients with metastatic malignancies to determine safety and pharmacokinetics of LY2157299, a small molecule inhibitor of the transforming growth factor-beta receptor I kinase
Authors: E. Calvo-Aller, J. Baselga, S. Glatt, A. Cleverly, M. Lahn, C. L. Arteaga, M. L. Rothenberg, M. A. Carducci
Journal: Journal of Clinical Oncology (2008)

14554 Background: Transforming Growth Factor beta (TGF-β) is an important cytokine regulating physiological processes, such as neoangiogenesis, immune responses and tissue remodeling. LY2157299 is a novel small molecule inhibitor which selectively targets the kinase domain of the TGF-β receptor type I. Methods: Patients with advanced/metastatic malignancies and who had exhausted all approved treatments were enrolled in this study. A pharmacokinetic/pharmacodynamic (PK/PD) model was developed based on pre-clinical studies to define starting doses and dose selection for this First Human Dose (FHD) study. Cohorts of 3 patients each were used to determine the safety and pharmacokinetics at the daily doses of 40 mg and 80 mg. Results: Seven patients (3 and 4 patients at the 40 mg and 80 mg dose, respectively) were enrolled in this study, who had colon cancer (n=3), prostate cancer (n=1), adrenal gland cancer (n=1), breast cancer (n=1) and melanoma (n=1). LY2157299 was well tolerated at both doses of 40 and 80 mg and no drug-related CTCAE Grade 3 or 4 toxicities were observed. The PK profile was consistent with the preclinical-based PK/PD modeling. Analysis of the 2 cohorts showed that absorption of LY2157299 was rapid as determined by plasma concentrations at the first sampling time (0.5 hours). The apparent clearance (CL/F) and the apparent volume of distribution (V/F) were estimated at 27.9L/h and 146.4L, respectively. Results from a formal statistical analysis suggested dose proportionality based on the observed AUC (0–12) and Cmax across the two doses. The mean t1/2 remained relatively constant and was estimated to be 6.5 hours. No definitive accumulation of LY2157299 was observed over the 56-day BID dosing regimen. Within and between patient coefficients of variation were 29% and 49% for AUC (0–12), respectively, and 33% and 78% for Cmax/Cmax,ss, pooled across the 2 cohorts. Conclusions: Daily oral administration of LY2157299 was safe and well tolerated at the two dose levels and the pharmacokinetic profile was consistent with the prediction derived from preclinical PK/PD model. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Eli Lilly Eli Lilly
Impact of preoperative CEA levels on the prediction of lymphnode (LN) metastasis
Authors: K. Danno, T. Sugimoto, M. Ikeda, K. Ikeda, T. Ohnishi, M. Fukunaga, H. Ohta, H. Mishima, M. Watase, M. Sekimoto, M. Monden
Journal: Journal of Clinical Oncology (2006)

20070 Background: Although CEA is the most commonly used tumor marker for colorectal carcinoma (CRC) and it may correlate with poorer prognosis, data are insufficient to support its use to determine adjuvant therapy. Monitoring preoperative CEA might be useful if it would assist in staging and treatment planning. Methods: This study was a pooled data analysis of 1791 CRC patients (pts) collected prospectively from 25 hospitals participating in the MCSGO. The purpose of this study was to investigate the impact of preoperative CEA on the prediction of the number of LN metastasis (#LN). Data of 1328 pts were completed with preoperative CEA and clinicopathological (CP) data (number of dissected LN, #LN, tumor size, distant metastasis, macroscopic type, depth of invasion, histological type, and lymphatic and vessel invasion). Data of 582 pts with the number of dissected LN 12 were analyzed in this study. #LN was categorized in 5 levels (0, 1, 2, 3, and ≥4), and relationship between #LN and CEA was first investigated via a multivariate analysis based on adjusting for the other CP factors. Discrete logistic regression analysis was used, in which a random effect was incorporated to adjust some bias between hospitals. The linear effects for the factors were evaluated via the regression model. The multivariate adaptive regression spline (MARS), the most powerful tool in the statistical prediction, was employed for the prediction of #LN. Results: The effect of the CEA adjusted by the other CP factors had a positive trend with two-sided P-value of 0.0394 for #LN. The adjusted R-squared measure (R 2 *) by the MARS fitting, a prediction performance index of #LN, was 0.369, and that averaged based on Bootstrap sampling (Bagging method) was R 2 * = 0.405. The relative importance of each factor in the prediction of #LN estimated by the decrease rate of R 2 * on masking each factor is shown in the Table . The relative importance of CEA in the prediction of LN# was ranked second next to lymphatic invasion. Conclusions: Preoperative CEA has a significant impact on the prediction of #LN. [Table: see text] No significant financial relationships to disclose.
Children born from infertility treatment are not at risk of developmental delays, study finds
Authors: Jacqui Wise
Journal: BMJ (2016)

Children conceived after infertility treatment are no more likely to have developmental delays than children conceived naturally, researchers have reported in JAMA Pediatrics .1

Concerns had arisen that conception after infertility treatment could affect the embryo at a sensitive stage and harm neurodevelopment. Many studies have investigated neurodevelopmental outcomes from assisted reproductive technology, but the evidence remains equivocal and is based largely on a few follow-up studies conducted outside the United States, said the study …
A liposomal MUC1 vaccine for treatment of non-small cell lung cancer (NSCLC): Differences in QOL assessments for Stage IIIBLR and IV patients
Authors: D. Soulières, N. Murray, A. Maksymiuk, E. Marshall, G. Goss, C. Butts
Journal: Journal of Clinical Oncology (2005)

7209 Background: The primary analysis results from a randomized, open label phase IIb trial utilizing L-BLP25 (BLP25 Liposome Vaccine) for the immunotherapy of stage IIIB and IV NSCLC patients with stable or responding disease following any first line chemotherapy were reported in April 2004. Patients were randomized 1:1 to best supportive care (BSC) or BSC + L-BLP25 (TX). Treatment arm patients received a single intravenous dose of 300mg/m2 cyclophosphamide, followed by 8 weekly subcutaneous immunizations with L-BLP25. Maintenance immunizations are given at 6-week intervals. The FACT-L QoL questionnaire was administered to all patients prior to study randomization, at weeks four and eight, and then every 12 weeks, commencing at week 19, until withdrawal/discontinuation from the study. Overall, a clear advantage for the L-BLP25 arm compared to BSC arm was demonstrated. More patients in the L-BLP25 arm demonstrated either a clinically meaningful improvement or did not change from baseline compared to patients in the BSC arm, where more patients demonstrated a clinically meaningful worsening in the Trial Outcome Index (TOI). Patients receiving L-BLP25 maintained QoL as measured by the FACT-L total score and TOI. Methods: Stage IIIBLR disease and Stage IIIB with malignant PE/IV subgroup comparison analysis between TX and BSC patients was performed for the FACT-L total score, subscales and TOI using T-test. Results: Of 171 patients enrolled, 65 had IIIBLR disease. The groups were well balanced. Results are presented in Table 1. Conclusion: The subgroup analysis indicates that the better QoL for patients treated with L-BLP25 is mainly dependant on StageIIIBLR patients. This is consistent with previously presented data demonstrating a clinically meaningful improvement in survival in Stage IIIBLR patients treated with BLP-25 (p=0.0692). Subscale scores will be presented at the meeting Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Biomira
Hospitalization for exacerbation of respiratory symptoms in former workers of a poison gas factory
Authors: Yoshifumi Nishimura, Nobuhisa Ishikawa, Hiroshi Takahashi, Masaya Taniwaki, Keiichi Kondo, Noboru Hattori, Nobuoki Kohno
Journal: European Respiratory Journal (2014)

Introduction: Exacerbation of chronic obstructive pulmonary disease (COPD) increases the rate of hospitalization. Since 1952 and for more than 60 years, we have provided health care to the former workers of a poison gas factory. Previous studies in our laboratories revealed a high incidence of COPD among these workers. However, exacerbation of respiratory symptoms among them has not been evaluated to date.

Objectives: We aimed to elucidate the clinical features leading to the hospitalization for exacerbation in former workers of a poison gas factory.

Methods: We retrospectively reviewed clinical records of 635 former workers of a poison gas factory, who underwent pulmonary function tests between 2009 and 2010. Hospitalization for exacerbation was defined as exacerbation of respiratory symptoms plus hospitalization.

Results: The mean annual hospitalization rates for exacerbation of former workers with and without COPD were 0.070 and 0.041 events per patient year, respectively. Among 51 patients who experienced at least one hospitalization for exacerbation during the 2-year observation period, 13 patients developed multiple hospitalization for exacerbation. Multivariate analysis showed that older age ( P = 0.003), current smoking status ( P = 0.01), and lower %FEV1 ( P < 0.001) were independent predictors of hospitalization for exacerbation.

Conclusions: Former poison gas workers, even those without lung function impairment, required frequent hospitalization for exacerbation. Our study suggests that older age, current smoking status, and lower %FEV1 are the important predictors of hospitalization for exacerbation in workers of poison gas factories.
Abstract 10720: Sitagliptin Provides Multiple Antiatherosclerotic Effects Independent of Diabetic Improvement for Type-2 Diabetics With or Without Insulin Therapies
Authors: Tatsuaki Murakami, Katsushi Misawa
Journal: Circulation (2012)

Background:  Diabetes mellitus is thought to be highly involved in complex atherothrombogenic processes, but the antiatherosclerotic therapies in diabetic patients have not been established.We assessed hypothesis sitagliptin, a dipeptidyl peptidase-4 inhibitor (DPP4I) recently developed antidiabetic agent, inhibits atherosclerotic progression in diabetic patients.   Methods:  Type-2 diabetic patients with or without insulin therapies were randomized to group-S where they received sitagliptin, or to group-C where they continued therapy without a DPP4I for 6 months. We quantified flow-mediated endothelium-dependent dilatation of brachial artery after 5 minutes forearm occlusion (FMD) using high-resolution ultrasonography, and we also quantified brachial-to-ankle pulse wave velocity (PWV). Changes in FMD and PWV were compared between the 2 groups.   Results:  The patients in group-S (n=18) manifested improvements in metabolic variables represented by HbA1c and LDL after medication, while those in group-C (n=18) showed no improvement. In group-S FMD (%) increased both in patients with insulin therapies (from 3.4±2.5 to 5.9±2.9, p=0.02) and in those without insulin therapies (from 3.9±2.1 to 6.5±2.8, p   Conclusion:  These results indicate sitagliptin provides multiple antiatherosclerotic effects independent of diabetic improvement, which may have novel potential benefit of a DPP4I for management of progressive atherosclerosis in type-2 diabetics with or without insulin therapies.
Detecting subclinical atherosclerosis (SA) in testicular cancer (TC) survivors
Authors: D. J. Vaughn, L. A. Jacobs, S. Palmer, J. Carver, E. Mohler, A. T. Meadows
Journal: Journal of Clinical Oncology (2005)

8163 Background: Studies suggest that TC survivors treated with cisplatin-based chemotherapy (CBCT) have increased cardiovascular risk (Meinardi, et al. J Clin Oncol, 2000; Huddart, et al. J Clin Oncol, 2003). Detection of SA in asymptomatic individuals could identify an at risk cohort for targeting behavioral and/or pharmacologic interventions. SA can be detected by measuring flow-mediated brachial artery vasodilatation (FMD), carotid artery intima-media thickness (IMT), and biochemical markers including ICAM and hsCRP. Methods: In this pilot study, we compared TC survivors who received CBCT with those who are chemo-naïve (CN) with respect to Framingham risk scores, brachial artery FMD, carotid artery IMT, and ICAM/hsCRP. Results: To date, 27 subjects have been enrolled: 16 received CBCT, 11 were CN. Median age of the CBCT subgroup is 41 years vs. 43 years for the CN subgroup. Both groups are approximately 6 years post-diagnosis. Both subgroups have an increased 10-year coronary heart disease risk compared to age-matched healthy controls as determined by Framingham (relative risk for CBCT subgroup: mean, 2.4; range, 0.75–9.25; relative risk for CN subgroup: mean, 1.6; range, 1.0–2.5; both p <.02). Brachial artery studies have been performed on 18 subjects. Both subgroups demonstrate impairment in endothelium-dependent brachial artery FMD (mean 6.8%; normal > 12%) but normal endothelium-independent nitroglycerin-mediated vasodilatation (mean 18.60%). No significant differences in brachial artery FMD were noted between the CBCT and CN subgroups. Carotid artery IMT was normal in subjects from both subgroups (n=15). ICAM and hsCRP are within the normal range in both subgroups. Conclusions: These preliminary results suggest that both CBCT and CN subgroups of TC survivors may have increased risk of coronary heart disease. In addition, both subgroups demonstrate abnormal brachial artery FMD, suggesting endothelial dysfunction. Accrual to this study continues. Further investigation of potential endothelial dysfunction in TC survivors may be warranted. Supported in part by NCI 1R21CA097355–01A1, Lance Armstrong Foundation, Abramson Family Cancer Research Institute. No significant financial relationships to disclose.
Sixty seconds on . . . malaria vaccination
Authors: Nigel Hawkes
Journal: BMJ (2015)

The World Health Organization has hedged its bets by recommending 3-5 large pilot projects to see how practicable the vaccine is. This falls short of a wholehearted recommendation but accurately reflects current uncertainty.

The genus of parasites that cause malaria, plasmodium, is a tough target. Much bigger and more complex than a bacterium or a virus, …
Inhibiting ABCG2 by Ko143 May Enhance the Efficacy of Irinotecan Treatment in Colon Cancer
Authors: Hoang Dinh Tuy, Hisanori Shiomi, Ken Ichi Mukaisho, Shigeyuki Naka, Hiroyuki Sugihara, Tohru Tani
Journal: Clinical Gastroenterology and Hepatology (2015)