tbuckley/cabot-search huggingface dataset:
Abstract 11860: Incremental Prognostic Significance of Peripheral Endothelial Dysfunction in Heart Failure With Reduced Left Ventricular Ejection Fraction
Authors: Koichiro Fujisue, Seigo Sugiyama, Yasushi Matsuzawa, Eiichi Akiyama, Koichi Sugamura, Junchi Matsubara, Hirofumi Kurokawa, Hirofumi Maeda, Yoshihiro Hirata, Hiroaki Kusaka, Eiichiro Yamamoto, Satomi Iwashita, Hitoshi Sumida, Kenichi Tsujita, Koichi Kaikita, Seiji Hokimoto, Kunihiko Matsui, Hisao Ogawa
Journal: Circulation (2014)

Background: Endothelial dysfunction plays a crucial role in heart failure (HF). However, relation between peripheral endothelial function and prognosis remains unknown in patients with HF with reduced left ventricular ejection fraction (HFREF). We investigated the relation between endothelial function and cardiovascular outcomes in HFREF patients. Methods: This is a two-center prospective cohort study of 362 HFREF patients (symptoms of HF and left ventricular ejection fraction [LVEF] <50%) between September 2006 and December 2012. Peripheral endothelial function was noninvasively assessed by reactive hyperemia peripheral arterial tonometry (RH-PAT) as the natural logarithmic scaled reactive hyperemia index (Ln-RHI). We followed HF-related events (composite of cardiovascular death and HF-hospitalization). Results: 82 HF-related events were recorded until 3-years follow-up. The lower-RHI group (Ln-RHI≤0.49, median) had a significantly higher probability of HF-related events compared to the higher-RHI group ...
Abstract 9998: Mechanisms Underlying the Impairment of Ischemia-Induced Neovascularization in Cathepsin K-Deficient Mic
Authors: Haiying Jiang, Xian Wu Cheng, Guo-Ping Shi, Lina Hu, Haizhen Song, Aiko Inoue, Teruhiko Koike, Masafumi Kuzuya
Journal: Circulation (2012)

Background : Cysteine protease cathepsins (Cats) have been implicated in the process of neovascularization. However, the exact roles of individual Cat proteins in vessel formation are poorly understood. Methods and Results : To study the putative role of cathepsin K (CatK) in ischemia-induced neovascularization, a hindlimb ischemia model was applied to CatK+/+ and CatK-/- mice. Serial laser Doppler blood-flow analysis revealed that the recovery of the ischemic/normal blood-flow ratio in CatK-/- young and old mice remained impaired throughout the follow-up period. At day 28, anti-L-lectin immunohistochemical staining revealed less developed capillary formation in both old and young CatK-/- mice compared with age-matched CatK+/+ mice. CatK deficiency reduced macrophage infiltration in the ischemic muscle. An aortic-ring culture assay showed a markedly impaired angiogenic response in CatK-/- mice. Aorta-derived endothelial cells and bone marrow-derived endothelial progenitor cell (EPC)-like c-Kit+ cells from CatK-/- showed marked impairment of invasive and proliferative abilities. On day 7, plasma and ischemic tissues of CatK+/+ showed reduce vascular endothelial growth factor protein and stromal cell derived factor-1. Flow cytometry showed that the numbers of EPC-like CD31+/c-Kit+ cells in peripheral blood markedly decreased in CatK-/- mice. Transplantation of bone marrow-derived mononuclear cells from CatK+/+ mice restored neovascularization in CatK-/- young mice. Conclusions : These data suggest that CatK deficiency impairs ischemia induced neovascularization through a reduction of endothelial cell and EPC functions and EPC mobilization.
p53 adapted neoadjuvant therapy for esophageal cancer: Pilot study
Authors: D. Kandioler, M. Hejna, R. Zwrtek, S. Kappel, C. Bichler, F. Wrba, A. Ba-Ssalamah, C. Zielinski, R. Jakesz, J. Zacherl
Journal: Journal of Clinical Oncology (2007)

4535 Background: Randomized trials could not yet prove clinical efficacy of neoadjuvant chemotherapy for esophageal cancer. A survival benefit could be shown for treatment responders only. Using platinum based regimen, yet about 20 % of patients can achieve pathological complete remission which translates in reported 3-year survival rates of 64% in this group. Factors identifying this subgroup of responders and selecting optimal drugs for non responders could dramatically enhance treatment efficacy. Several studies suggest that mutations in the p53 gene may induce drug resistance especially for agents whose effect is based on apoptosis induction, like Cisplatin. Methods: In order to test the hypothesis that the p53 genotype is predictive for chemotherapy response, a prospective study was conducted. Thirty-eight patients with potentially respectable esophageal cancer were evaluated for the relation between p53 genotype and response to two different neoadjuvant treatments. P53 gene mutations were assessed by complete direct sequencing of DNA extracted from diagnostic biopsies. Response to neoadjuvant chemotherapy was assessed pathohistologically in the surgical specimen. Results: 20 squamous cell carcinoma and 18 adenocarcinoma were included. Overall the p53 mutation rate was 58% (22/38), with 66 % for squamous cell and 53% for adenocarcinomas, respectively. 30 patients received CIS/5FU (cisplatin 80mg/m 2 d1 5-FU 1,000mg/m 2 d 1–5, q21,2 cycles), 8 received docetaxel (75mg/m 2 , q21,2 cycles). The overall response rate was 48% (18/38). Patients with p53 mutation did not respond to CIS/5-FU (0/16), while all mutant patients responded to docetaxel (6/6). The overall response to p53 adapted neoadjuvant therapy was 94%. P53 adapted treatment was associated with a significant survival advantage (p=0,042) after a median follow up of 15,4 months. Conclusions: A prospective randomized trial was initiated to test the interaction between the predictive marker p53 and response to CIS/5-FU and Docetaxel, respectively. [Table: see text] No significant financial relationships to disclose.
Association of KRAS mutations in cell-free circulating tumor DNA with occurrence of resistance to TKIs in NSCLC.
Authors: Marzia Del Re, Lorenza Landi, Marcello Tiseo, Andrea Camerini, Iacopo Petrini, Alessandro Inno, Valentina Citi, Jessica Salvini, Gabriele Minuti, Enrico Vasile, Alfredo Falcone, Stefania Gori, Domenico Amoroso, Andrea Ardizzoni, Federico Cappuzzo, Romano Danesi
Journal: Journal of Clinical Oncology (2014)

11056 Background: EGFR activating mutations predict sensitivity to tyrosine kinase inhibitors (TKIs) in NSCLC. Although initial responses are commonly observed, patients inevitably progress as a consequence of acquired resistance. Secondary mutations in the EGFR domains (Gainor JF, Shaw AT. J Clin Oncol 2013;31:3987) or in cross-talking pathways (i.e., KRAS, Martin P, et al. J Thorac Oncol 2013;8:530) have been detected in biopsies of resistant cancers. However, the location of the tumor and the risk of complications are serious limitations to re-biopsies in NSCLC. Alternatively, detection of somatic mutations in circulating cell-free DNA (ccfDNA) in plasma could be instrumental to a better understanding of the dynamics of the genetic shift of tumors under stress conditions caused by drug treatments. Methods: Twenty-eight NSCLC patients displayed an activating EGFR mutation or ALK translocation in the primary tumor and received a TKI against EGFR (gefitinib or erlotinib, n= 25) or ALK (crizotinib, n= 3). Blood (5 ml) was collected after tumor progression and DNA was extracted from plasma using QIAamp circulating nucleic acid kit and tested for EGFR and KRAS mutations using Rotor-Gene Q PCR (Qiagen, Valencia, CA) or digital droplet PCR (Bio-Rad, Hercules, CA). Results: EGFR mutations of the primary tumor were confirmed in ccfDNA of 35.7% patients after progression under TKIs (L858R 7.1%, exon 19 insertions/deletions 28.6%). The EGFR T790M mutation was in 10.7% of patients’ ccfDNA. Interestingly, 10 (35.7%) patients displayed a codon 12 KRAS mutation in ccfDNA, including all patients with ALK+ tumors, after TKI treatment. The KRAS mutations were not detectable in their primary tumor using conventional diagnostic approaches. Pre-treatment plasma samples were available in only two patients and KRAS mutations were not detected. Conclusions: The observation of KRAS mutations in plasma of patients with tumors carrying EGFR mutations or ALK rearrangements after TKI treatment suggests an important role of this oncogene in acquired resistance.
Differential delays in breast cancer treatment as a function of racial/ethnic background
Authors: R. T. Bustami, E. B. Poletick, J. N. Cosico, E. D. Whitman
Journal: Journal of Clinical Oncology (2007)

17023 Differential delays in breast cancer treatment as a function of racial/ethnic background Background: Multiple studies have identified differences in breast cancer treatment and outcome due to racial/ethnic and socioeconomic factors. The purpose of this study was to investigate treatment disparities, both actual and temporal (i.e. time delay), in patients newly diagnosed with breast cancer as a function of racial/ethnic background. Methods: Patients at two affiliated hospitals newly diagnosed with breast cancer were identified and classified from discharge billing data. Time to treatment was defined as the time in days between biopsy proven diagnosis and initiation of treatment including chemotherapy, radiation therapy, lumpectomy and mastectomy. Nonparametric Analysis of Variance (ANOVA) using the Kruskal-Wallis Test examined differences between race groups based on median time to treatment. Types of treatment were analyzed by the Chi-Square test. Results: A total of 1217 patients were identified over a five-year period. Racial background was classified as White, African American, or Asian/Other. Lumpectomy was performed in 47%, 41%, and 38%, respectively (p = 0.15), while 24%, 23%, and 18% received a mastectomy (p = 0.51). There were no significant differences between the racial groups for types of therapy received. Results from ANOVA (table) showed statistically significant differences between the three race groups in terms of time to mastectomy (p = 0.003) and time to radiation therapy (p=0.043). Results from pairwise comparisons showed that (1) African American patients had a significantly longer time to mastectomy than Whites (p = 0.002), (2) patients in the Asian/Other group had a significantly longer time to radiation than their white counterparts (p = 0.015). Conclusion: This study demonstrates racial differences in time to non-surgical and surgical treatment in a group of ethnically diverse breast cancer patients. [Table: see text] No significant financial relationships to disclose.
A randomized controlled trial to evaluate the impact of an educational DVD on cancer patients considering participation in a phase I clinical trial
Authors: E. L. Strevel, C. Newman, G. R. Pond, M. Maclean, L. L. Siu
Journal: Journal of Clinical Oncology (2006)

6011 Background: Informed consent for phase I trials is controversial; gaps in patient (pt) knowledge regarding the purpose of these studies are central to this debate. This study assessed the impact of viewing an educational DVD on pt knowledge and satisfaction in cancer pts newly referred to a phase I trials clinic. Methods: Prior to physician (MD) appointment, 49 pts were randomly assigned to view either an educational DVD (n = 22) which provided information about phase I trials, or a placebo DVD (n = 27) which described research achievements by local scientists. Upon completion of DVD viewing, pts completed a self-administered questionnaire addressing their understanding of phase I trials (knowledge) and their satisfaction with the DVD (perception). The interviewing MD (n = 8), who was blinded to the intervention, also rated the pt’s understanding of phase I trials upon completion of the clinic appointment. Results: The mean pt age was 56 and 61% were male. Prior to attending the phase I clinic, most pts (86%) had previously heard of clinical trials, but only 49% were aware of phase I trials. Pts who viewed the educational DVD were less likely to believe that the goal of phase I trials is to determine the efficacy of a new drug (p = 0.019), more likely to correctly assess that drugs undergoing phase I evaluations have not been thoroughly studied in humans (p = 0.003), and less likely to believe that phase I drugs have proven activity against human cancers (p = 0.008). More pts who viewed the educational DVD than the placebo DVD agreed/strongly agreed that the DVD provided useful information (p &lt; 0.001), believed that they had a good knowledge of phase I trials (p = 0.031), felt that the DVD helped them decide whether to enter a phase I trial (p = 0.011), and perceived that they would have more questions for their physicians as a result of watching the DVD (p = 0.017). No statistically significant differences in MD satisfaction was observed. Conclusions: Exposure to an educational DVD increased both objective measures of pt knowledge as well as pt satisfaction regarding participation in phase I clinical trials. The educational DVD did not significantly impact MD perception of pt understanding. No significant financial relationships to disclose.
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Authors: J Vaage
Journal: JNCI Journal of the National Cancer Institute (1984)

The anterior-posterior incidence of spontaneous mammary tumor development and the anterior-posterior gradient of growth potential among transplanted tumors was studied in C3H/He and C3Hf/He mice. The relative incidence of spontaneous tumor development in the five mammary gland pairs showed no anterior-posterior bias, but it was in proportion to the quantity of tissue in the individual mammary glands. The transplantability and growth rate of 164 spontaneous C3H/He and 67 spontaneous C3Hf/He mammary carcinomas were tested and compared in anterior and posterior subcutaneous sites and at mammary implantation sites. Initially, in their early transplant generations, most subcutaneous tumor implants (67%) grew significantly better near the shoulder than in an implantation site near the hip. At the same time, implants from the same tumor tissue grew equally well in anterior (#2) and posterior (#4) mammary glands. Without exception, all transplanted tumors grew better in a mammary gland than at a subcutaneous site. Some tumors (12%) that initially would grow only in mammary glands gained subcutaneous transplantability with increased growth rate. With increasing growth rate, the tumors' anterior subcutaneous growth preference decreased. Anterior subcutaneous growth preference was not related to immunologic tumor characteristics. Implants of slow-growing tumors grew better in the anterior subcutaneous implantation site where the greater blood flow improved their growth conditions and survival rate.
Relationship of DNA Viruses and Cervical Carcinoma
Journal: JNCI Journal of the National Cancer Institute (1985)

Journal Article Relationship of DNA Viruses and Cervical Carcinoma Get access Susan B. Spring, Ph.D., Susan B. Spring, Ph.D. Biological Carcinogenesis Branch Division of Cancer Etiology National Cancer Institute National Institutes of Health Public Health Service U.S. Department of Health and Human ServicesBethesda, Maryland 20205 Search for other works by this author on: Oxford Academic PubMed Google Scholar Jack Gruber, Ph.D. Jack Gruber, Ph.D. Biological Carcinogenesis Branch Division of Cancer Etiology National Cancer Institute National Institutes of Health Public Health Service U.S. Department of Health and Human ServicesBethesda, Maryland 20205 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 75, Issue 3, September 1985, Pages 589–590, https://doi.org/10.1093/jnci/75.3.589 Published: 01 September 1985
Factors associated with reductions in chemotherapy dose intensity: Impact of clinical, sociodemographic and practice setting
Authors: G. H. Lyman, N. M. Kuderer, M. S. Poniewierski, J. Crawford, D. A. Wolff, E. Culakova, D. C. Dale
Journal: Journal of Clinical Oncology (2007)

6550 Background: A nationwide, prospective cohort study of patients receiving cancer chemotherapy was undertaken to better define treatment-associated toxicities and delivered dose intensity. Methods: Following informed consent, 3,670 patients initiating a new chemotherapy regimen with lymphoma (n=547) or carcinomas of the colon (n=521), breast (n=1,473), lung (n=907) or ovary (n=312) were prospectively registered at 117 randomly selected US oncology practices between March 2002 and December 2005. Pretreatment characteristics including clinical and sociodemographic factors and practice setting associated with reductions in chemotherapy dose intensity over 4 cycles were evaluated. Results: Chemotherapy regimen standards and intended dose and schedule were defined in 97% and 93% of patients, respectively. Average initial (planned) relative dose intensity (RDI) was 90% while the mean RDI actually delivered over 4 cycles was 83%. Reductions in RDI =15% of standard were planned in 23% of patients and actually occurred over 4 cycles in 38%. Body surface area (BSA) calculated by the method of Mosteller exceeded the BSA utilized by the oncology practices in two-thirds of patients most often due to capping at 2 m 2 . Obese patients with a body mass index (BMI) =30 were more likely to receive planned RDI reductions =15% (30%) than patients with BMI &lt;30 (21%) (P&lt;.0001). Other factors associated with planned reductions in RDI in multivariate analysis included: older age, male gender, lower education, absence of myeloid growth factor prophylaxis and cancers of the lung or ovary as well as the practice setting, size and geographic location. Factors associated with unplanned (subsequent) reductions in RDI included: older age, male gender, poorer Charlson comorbidity index, prior chemotherapy, lung cancer, low baseline hematocrit, white blood or platelet count, poor renal or hepatic function and low serum albumin as well as smaller practice and rural setting. Conclusions: A substantial proportion of patients receiving cancer chemotherapy experience both planned and unplanned reductions in RDI. Further understanding of factors associated with such reductions may provide opportunities for improving the quality of cancer care and clinical outcomes. No significant financial relationships to disclose.
Randomized phase III trial of the TTD Group comparing capecitabine and oxaliplatin (XELOX) vs. oxaliplatin and 5-fluorouracil in continuous infusion (FUFOX) as first line treatment in advanced or metastatic colorectal cancer (CRC)
Authors: B. Massuti, A. Gómez, J. Sastre, J. M. Tabernero, M. Chaves, A. Carrato, A. Abad, J. Aparicio, E. Díaz-Rubio, E. Aranda
Journal: Journal of Clinical Oncology (2006)

3580 Background: OX plus CI 5-FU is one of the standard chemotherapy regimens for first-line treatment in patients (p) with advanced CRC. Phase II trials have shown XELOX as a convenient combination, with a high activity and a favourable safety profile. This study is a phase III trial comparing both schedules. Methods: Multicenter, randomized and open labeled study was designed to include p withadvanced/metastatic CRC adenocarcinoma, measurable disease, PS ≥70% and adequate bone marrow, renal and hepatic functions. Previous adjuvant chemotherapy was allowed. Primary endpoint is time to progression (TTP). The study was designed to determined non-inferiority when the median time to progression in the XELOX arm was not lower than 5.5 months (hazard ratio no larger than 1.27). A sample size of 348 p (174 per arm) was necessary (0.05 level test; 80% power). Treatment: P were randomly assigned to receive either Arm A: oral XEL 1000 mg/m 2 twice daily from day 1 to day 15, plus OX 130 mg/m 2 , iv, 2h, day 1 (in 3-week treatment cycles) or Arm B: biweekly 85 mg/m 2 , OX, iv, 2h, plus weekly CI 5-FU 2250 mg/m 2 , in 48h (TTD schedule). Treatment was continued, until progressive disease, unacceptable toxicity or consent withdrawal. Results: 340 (170/170) p have been included in the interim analysis over 348 enrolled, (M/F, 61%/39%), median age: 65.6 years (32.3–81.6), PS 90–100%: 62%. Primary tumour sites were colon (66.4%), rectum (28.3%) and both (5.3%). Median relative dose intensity was 90% for XEL and 92% for OX in arm A and 78% for OX and 78% for 5-FU in arm B. Efficacy: overall response rate in each arm (A/B) was 37.1/43.0% (p=0.824). With a median follow up of 12.6 months, median TTP was 8.8/9.6 months (p=0.130). Main grade 3–4 toxicity per p in each arm (A/B) was: paresthesia (17.7/15.9%), asthenia (12.4/17.1%), diarrhea (14.1/23.6%), neutropenia (8.3/10.0%) and vomiting (4.1/7.6%). Mature data on TTP and OS will be presented at the meeting. Conclusions: Efficacy and safety results suggest a similar toxicity profile, response rate and TTP for both regimens. No significant financial relationships to disclose.
Mechanism of bevacizumab-induced arterial hypertension: Relation with skin capillary rarefaction in patients treated for metastatic colorectal cancer
Authors: J. F. Morere, G. Des Guetz, J. Mourad, B. I. Lévy, J. Breau
Journal: Journal of Clinical Oncology (2007)

3557 Background: Bevacizumab in combination with chemotherapy is the standard treatment of metastatic colorectal cancer (mCRC). Hypertension (HT) has been reported in all studies, in particular grade 3 HT (3 - 16%) (Saif and Mehra, 2006 Expert Opinion on Drug Safety). The mechanism underlying bevacizumab-related HT is not yet clearly understood and recent studies have demonstrated that humoral factors involving the renin-angiotensin system and the sympathetic nervous system had little role in the observed increase in BP. As far as microvascular rarefaction has been reported in all forms of human and experimental HT, we tested the hypothesis that anti VEGF therapy could induce microvascular rarefaction in non tumoral tissues and, thus, result in an increase in BP Methods: For 16 patients treated for mCRC, Bevacizumab was administered at 5 or 7.5 mg/kg every 2 or 3 weeks depending on the frequency of concomitant chemotherapies which were FOLFIRI (4 patients) or XELOX (12 patients) We used intravital video-microscopy to measure basal and maximal (during venous congestion) skin capillary densities in the dorsum of the fingers. Aortic stiffness was evaluated using pulse wave velocity, and microvascular endothelial function was assessed by laser-Doppler flowmetry combined with iontophoresis of three different doses of acetylcholine (ACh). All measurements were performed in 16 patients (mean age: 59±10 y) before and after a 6 month treatment with bevacizumab (mean cumulative dose: 3.16±0.90 g) Results: are summarized in the following table : Conclusions: Pharmacological blockage of VEGF receptors result in endothelial dysfunction and capillary rarefaction in humans. Both changes are closely associated with and seem responsible for the rise in blood pressure observed in patients receiving this treatment. This could be considered for future study about anti- angiogenic treatment and HT. [Table: see text] No significant financial relationships to disclose.
How early starts increased collagen synthesis in systemic sclerosis
Authors: F Ingegnoli, R Gualtierotti, T Schioppo, A Orenti, P Boracchi, C Lubatti, A Murgo, S Zeni, C Mastaglio, Galbiati, G Monti, C Grossi, O Borghi, W Rosenberg, PL Meroni
Journal: Annals of the Rheumatic Diseases (2013)