tbuckley/cabot-search huggingface dataset:
Abstract 18995: Radiation-Induced Constrictive Pericarditis(r-cp) With Normal Left Ventricular Ejection Fraction is Associated With Lower Global and Regional Myocardial Mechanics Compared to Non-Radiation-Induced Constrictive-Pericarditis(cp)
Authors: Mamotabo R Matshela, Lori A Blauwet, Patricia A Pellikka, Jae K Oh, Hector R Villarraga
Journal: Circulation (2013)

Background: CP/R-CP may be associated with subtle features of ventricular dysfunction which are not easily detectable with the use of conventional echocardiographic modalities. The aim of this study was to evaluate myocardial mechanics by 2D-STE (2 Dimensional speckle-tracking echocardiography) between CP and R-CP. We hypothesized that strain/ strain rate (S/SR) would be worse in the R-CP patients due to radiation-induced myocardial injury. Methods: We analyzed 180 patients (62% male, age 62±13 years, 127 CP and 53 R-CP) with suitable echocardiographic images and normal left ventricular ejection fraction (LVEF&gt;55%). The two groups were similar in terms of age, cardiovascular symptoms, risk factor profile and LVEF (Table). Selected images were analyzed off-line using Velocity Vector Imaging technology. The diagnosis of CP was based on clinical parameters as well as echocardiography and/or hemodynamic cardiac catheterization. Patients in whom radiation therapy was the primary etiology of CP were classified as R-CP. Global and segmental circumferential, radial, longitudinal, systolic and early diastolic strain and strain rate were analyzed in all patients. Results: Global and segmental radial (GRadS), global longitudinal (GLS), global basal (GBS), global mid-segment (GMS), septal wall (SWS), and anterior wall (AWS) strain was significantly reduced in the R-CP patients compared with the CP patients (Table). Antero-septal and anterior wall diastolic strain and strain rates (AS + AW Sre, SR) were reduced in the R-CP group. The best differentiators between the two groups were antero-septal (SAS), basal anterior (BAS) and mid anterior (MAS) segmental strain, based on receiver operating characteristic (ROC) and area under the curve (AUC) analysis. ROC calculations were AUC: SAS 0.67, SBA 0.69, and SMA 0.71. Conclusion: The study showed that compared with CP, R-CP is associated more with myocardial dysfunction, likely due to radiation-induced myocardial injury.
Evaluation of prognosis in relapsed germ cell tumors: Identification of patients who profit from high dose chemotherapy (HDCT)
Authors: C. Sammler, J. Beyer, C. Bokemeyer, J. Hartmann, W. Siegert, O. Rick
Journal: Journal of Clinical Oncology (2006)

4585 Background: To identify prognostic variables in patients (pts) with metastatic germ cell tumors (GCT) and relapse or progression after first-line chemotherapy (FLC). Methods: In our database of 257 GCT pts treated with HDCT, 176/257 (67.4%) pts with first relapse or progression were identified. All patients had received platinum-based FLC. As salvage treatment all pts had received 1–3 cycles of conventional-dose salvage chemotherapy (CDCT) followed by one cycle HDCT. First, pts were retrospectively classified according to a prognostic score developed for CDCT by Fossa et al. [Br J Cancer 1999,80:1392], based on variables present at the time of relapse. Thereafter, a multivariate analysis was performed to evaluate further risk factors. Results: After a median follow up of 9 years the event-free survival (EFS) and overall survival (OS) for all 176 patients was 34% and 38%, respectively. Patients with good (n= 100/176, 57%) and poor (n = 76/176, 43%) prognosis in accordance to Fossa et al. showed an EFS of 41% and 26% (p &lt; 0.01) and an OS of 47% and 26% (p &lt; 0.01). Thus, in contrast to the data of Fossa et al, long-term survival could be demonstrated even in the poor prognosis subset. In the multivariate analysis, the level of elevated tumor markers alfa-fetoprotein and human chorionic gonadotrophin (p &lt; 0.01), the presence of extrapulmonal visceral metastases (p &lt; 0.01) and refractoriness to cisplatin (p &lt; 0.01) adversely influenced OS after HDCT significantly. Based on these latter factors three different groups with increasingly poor OS could be identified: none factor (n = 39/176, 22%) 4 year OS of 59%, one factor (n = 78/176, 44%) 6 year OS of 42% and more than one factor (n = 59/176, 34%) 4 year OS of 17%. Conclusion: In pts with first relapse or progression after platinum-based FLC high serum tumor markers, presence of extrapulmonal visceral metastases and cisplatin refractoriness proved to be independent prognostic significance for OS after salvage HDCT. However, even in the poor prognosis subset long-term survival could be demonstrated. No significant financial relationships to disclose.
Patients’ characteristics and outcomes of palliative care inpatient consults at a comprehensive cancer center
Authors: B. El Osta, F. S. Braiteh, S. Reddy, H. El Osta, E. Bruera
Journal: Journal of Clinical Oncology (2006)

8524 Background: There is limited information about the characteristics and outcomes of inpatient palliative care consults in cancer centers. Two mobile teams (MT) each with a physician, fellow, and a nurse, provide consultation to hospitalized patients (pts) with complex symptoms. Methods: We analyzed the pts characteristics and outcomes during a two-month period. The charts were reviewed for demographics, cancer data, reason for consultation, symptoms, interventions, and outcomes. Results: Sixty-one pts were analyzed. Pain was the main reason for a consult request in 46 pts (75%), delirium in 10 (16%), anxiety in 4 (7%) and constipation in 5 (8 %). Some pts had more than one reason. 56(92%) pts had metastatic disease, diagnosis for ≤1 year in 26 (42%) and ≤2 years in 44 (72%) (Median =17 months). The Edmonton Symptom Assessment Scale (ESAS), 0–10, is summarized in the table. We uncovered new issues at consultation, such as 20 pts (38%) screened positive for alcoholism with CAGE questionnaire and the 34 pts (56%) had clinical delirium. Features of opioids toxicity such as constipation (N=43;70%), confusion (N=35;57%) (Mean MMSE = 23 ± 5), hallucinations (N=21;34%), myoclonus (N=16;26%) and miosis (N=18;29%) were frequently identified. The MT interventions included imaging studies (23%), enema (43%), laxatives (49%), neuroleptics (54%), metoclopramide (39%), corticosteroids (25%). Half (N=30;50%) of the pts had opioid rotation and/or had counseling (N=27;46%). One out of two pts (N=30;49%) required transfer to the palliative care unit. Conclusions: Most pts had previously undiagnosed opioid toxicity, delirium, and other symptoms. Opioid toxicity occurred secondary to rapid opioid escalation, possibly linked to chemical coping, and psychosocial distress. The outcome of these pts improved by opioid rotation, adding laxatives, metoclopramide, neuroleptics, and steroids. [Table: see text] No significant financial relationships to disclose.
Margaret McCartney: Dishonourable New Year honours
Authors: Margaret McCartney
Journal: BMJ (2016)

This is likely to upset some of my nicest friends—those called Sir or Dame, or those who sign off with CBE or OBE (commander or officer of the Most Excellent Order of the British Empire). I apologise wholeheartedly. But, as the newspapers publish the names of those who have accepted the honours of the land in the New Year Honours list, and as the medical press publishes them to inevitable looks of envy, there should be room for caution.

To what extent does our honours system encourage people to think that it’s better to work on the inside of an institution rather than the outside? Clearly, some people genuinely think that insiders have a more direct route to …
Expression and activation of ADAM15 in bladder cancer
Authors: A. Bucheit, K. Day, M. L. Day, W. A. Chadwick, M. Liebert, M. Hussain
Journal: Journal of Clinical Oncology (2009)

e16010 Background: ADAM15 is a member of the disintegrin family of metalloproteinases. These molecules function as membrane-bound proteases, and, when activated, cleave important membrane anchored growth factors such as heparin binding epidermal growth factor and cell adhesion molecules such as E-cadherin. This proteolysis may contribute to bladder cancer growth through release of growth factors and progression by altering cell adherence. We evaluated ADAM15 expression in bladder cancer cell lines and tissues. Methods: ADAM15 expression was assessed in human bladder cell lines, normal bladder and bladder cancer tissues. A datamining program (Oncomine) was used to evaluate previous array studies in bladder cancer. ADAM15 activation results in the release of a prodomain fragment. Expression and activation of ADAM15 in bladder cancer cell lines were monitored by enzyme-linked immunosorbent assay and western blotting using ADAM15 antibody (Millipore). Staining was performed on formalin-fixed, paraffin-embedded human tissues using ADAM15 antibody (Millipore) and the peroxidase- avidin-biotin complex (ABC) method. Results: Of 7 bladder cancer cell lines, 6 demonstrated expression of full length (100 kD) and “active” (90kD) ADAM15 molecules. Four of these cell lines showed release of the ADAM15 prodomain fragment, and 5 cell lines provided evidence for proteolytic activity, indicated by release of 80kD soluble E-cadherin molecule. Immunostaining of a bladder cancer tissue microarray revealed that normal urothelium expressed low levels of ADAM15, but focal overexpression of ADAM15 was observed in 17/29 bladder cancer specimens. Datamining of independent microarray analysis revealed that ADAM15 mRNA is upregulated in bladder cancer. Conclusions: ADAM15 is expressed in the majority of human bladder cancer specimens. Cell line studies indicate that ADAM15 can be activated, as indicated by release of the ADAM15 prodomain fragment. These results suggest that ADAM15 may be a therapeutic target to modulate bladder cancer growth and progression. Future studies will continue evaluation of the biology of ADAM15 in bladder cancer and evaluate if the soluble ADAM15 prodomain can be detected in plasma, serum or urine from patients with bladder cancer. No significant financial relationships to disclose.
Abstract 10787: Discovery of a Novel Aptamer-based Inhibitor of GPVI and its Matched Active Control Agent
Authors: Christopher P Rusconi, Juliana M Layzer, Brian G Stell, Sanjoy K Mahanty, Ryan J Quick, Tadeusz K Wyrzykiewicz, Douglas G Brooks, Steven L Zelenkofske
Journal: Circulation (2010)

Introduction: GPVI mediates collagen induced platelet activation and is required for firm adhesion of platelets to the damaged vessel wall. GPVI is also overexpressed in type 2 diabetes, and high G...
Erlotinib as 1st-line therapy for elderly patients (pts) with advanced non-small cell lung cancer (NSCLC)
Authors: O. Merimsky, C. Cheng, M. Reck, S. Au, J. von Pawel
Journal: Journal of Clinical Oncology (2008)

19016 Background: The prognosis for elderly pts with advanced NSCLC is generally poor due to significant co-morbidities that limit treatment options. Furthermore, aggressive treatments are often contra-indicated due to poor performance status. Erlotinib is approved as a 2nd-line therapy for pts with NSCLC, and is a useful treatment option for elderly pts due to its favorable toxicity profile. However, experience with 1st-line erlotinib in chemo-naïve elderly pts is currently limited. Methods: The global open-label TRUST study investigated erlotinib in >6000 pts with advanced stage IIIB/IV NSCLC. Pts were eligible if they had either failed standard treatment or were unsuitable for chemotherapy/radiotherapy. This report focuses on a subgroup of elderly pts (>70 y), who received erlotinib (150 mg/day) as a 1st-line therapy for advanced NSCLC. Results: By August 2007, eligible pts had received at least one dose of erlotinib and interim analysis data were available for 451 pts. Median age was 78 yrs and baseline characteristics (%) were as follows: male/female 57/43; never smoker/current or former smoker/no data 30/69/1; stage IIIB/V 31/68; adenocarcinoma/BAC/ squamous-cell/other 51/12/22/15; Caucasian/Asian/other 76/15/9. Grade 3–5 adverse events (AEs) of any cause were reported by 49% of pts. However, only 7% had ≥1 treatment-related AE, and only 3 pts (<1%) died due to a treatment-related AE (1 as a result of bleeding, 1 from pneumonitis, and 1 from community-acquired pneumonia). Dose reductions were necessary in 16% of pts. Five complete (1%) and 34 partial responses (8%) were noted. Stable disease was seen in 45% of pts for an overall disease control rate of 54%. Progression-free survival (PFS) was 16.4 wks (95% CI: 14.6- 20.0). This compares favorably with recent data, which demonstrated PFS of around 14 wks for pemetrexed or pemetrexed/gemcitabine in chemo-naïve pts >70 yrs [Gridelli et al, J Thorac Oncol 2007;2:221–9]. Overall survival data will be presented. Conclusions: Erlotinib as 1st-line treatment for elderly pts with NSCLC has encouraging efficacy. These results indicate that erlotinib is a valuable 1st-line treatment option for the management of advanced NSCLC in this subgroup and warrants further investigation in the 1st-line setting. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Boehringer Ingelheim, Hoffmann-La Roche, Lilly Bayer HealthCare, Boehringer Ingelheim, Hoffmann-La Roche, Lilly
A DNA vaccine targeting Flk1 and PDGFRβ prevents colon carcinoma growth
Authors: Charles D. Kaplan, Ralph R. Reisfeld
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

6176 

Over the past several years, it has become evident that angiogenesis plays a central role in tumor progression. One treatment approach which attempts to block tumor growth through the disruption of the anigogenic process, is the use of DNA vaccines encoding proteins that are over-expressed during angiogenesis. Two such proteins are vascular endothelial growth factor receptor-2 (Flk1) and platelet derived growth factor receptorβ (PDGFRβ). To assess the efficacy of inhibiting tumor growth by targeting cells expressing these proteins, BALB/c mice were immunized orally with attenuated salmonella thyphimurium carrying plasmid DNA encoding for empty vector, Flk1, PDGFRβ, or both Flk1 and PDGFRβ followed by i.v. tumor challenge with the colon carcinoma cell line CT26. Following challenge, disease severity was significantly reduced in all treatment groups except empty vector vaccinated control mice. Mice immunized with the PDGFRβ vaccine demonstrated a small, but statistically significant decrease in lung weight in comparison to controls, whereas both the Flk1 and the Flk1 plus PDGFRβ combination vaccination groups revealed a marked decrease in lung weight compared to controls. When mice were immunized with either the PDGFRβ or Flk1 vaccine alone, they displayed a significant decrease in the number of lung metastases in comparison to controls, whereas mice receiving a Flk1 plus PDGFRβ combination vaccine showed a more pronounced decrease in the number of lung metastases compared to all other treatment groups. Although PDGFRβ or Flk1 vaccinated groups demonstrated a decrease in overall metastasis score in comparison to controls, a vaccine including both Flk1 and PDGFRβ also proved superior in decreasing the metastasis score in comparison to all other treatment groups, suggesting that a combined Flk1 plus PDGFRβ vaccine regimen was more effective than a single vaccine application. To explain the protective effect of our DNA vaccines, we performed a CTL assay using splenocytes harvested from vaccinated/challenged animals and Hevc endothelial target cells (Hevc-Flk1), which endogenously expressed PDFGRβ and were stabley transfected with Flk1. Upon co-culture of the effector splenocytes with the Hevc-Flk1 target cells, we found that mice immunized with the Flk1 plus PDGFRβ combination vaccine induced the greatest cytolysis against Hevc-Flk1 target cells followed by mice immunized with either the Flk1 or PDGFRβ vaccine. Together, these results suggest that the use of a combined Flk1 plus PDGFRβ vaccine provides for superior protection from tumor progression than by immunizing mice against either target alone. These results further suggest a direct correlation between the level of the CTL response and level of protection conferred by the vaccine.
Abstract #LB-166: Promoter CGI methylation of reprogramming factors in aggressive B-cell lymphomas
Authors: Deiter Duff, Srilatha Nalluri, Michael Wang
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

Background: Both cancer and pluripotent stem cell lines share the common biological properties of unlimited capacity for self-renewal and high potency for proliferation in vitro . Several research groups have shown that differentiated somatic cells derived from all three germ layers can be induced into pluripotent stem cells (iPS) by defined transcription factors, namely OCT4, SOX2, c-MYC, KLF4, NANOG, and LIN28. Overexpression of a set of 4 genes induces global epigenetic reprogramming that in turn results in eventual transition of somatic cells to phenotypic iPS cells in a few weeks. Among these genes, OCT4 and SOX2 are required for self-renewal, while c-MYC and KLF4 are known to be oncogenic. Furthermore, xenograft of iPS cells in mouse produces a teratoma. It seems that there is not clear distinction between iPS cells and tumor cells. In this study, we demonstrated that the promoter CpG islands (CGIs) of SOX2 and KLF4 are methylated in two aggressive B-cell lymphomas, diffuse large B-cell lymphoma (BLBCL) and Burkitt lymphoma (BL). The latter is the most aggressive lymphoma characterized by a t(8;14) translocation resulting in overexpression of the c-MYC protein. Materials and Methods: DLBCL (DB) and BL (Raji and Daudi) cell lines from the American Type Culture Collection were studied. We also examined DLBCL (3) and BL (2) patient samples obtained from Ellis Fischel Cancer Center, University Missouri Healthcare, with IRB approval. Genomic DNA was extracted and subjected to digestion with 4 methylation sensitive restriction enzymes. Each of the PCR target in CGI was carefully selected and hypermethylated region can be differentially amplified. Results: CGI methylation of 10 genes was tested. These genes include SOX2, KLF4, HOXD10, COX2, DLC-1, PCDHGA12A, HIN1, SLC26A, CDH1, and CD44. Dense methylation of the SOX2 gene was observed in all 3 cell lines and 1 DLBCL patient. Only weak methylation bands were seen in all other patients. KLF4 was strongly methylated in all 3 cell lines and all DLBCL patients, but not methylated in BL patients. The HOXD10, COX2, DLC-1, SLC26A, CDH1, CD44 were methylated in both DLBCL cell lines and patient samples as well as in BL cell lines, but not in BL patient samples. No methylation was seen in pooled normal control blood samples. Conclusion: Promoter CGI hypermethylation in combination with other epigenetic alterations is associated with gene silencing. Compared with DLBCL, less CGI methylation of reprogramming factors SOX2 and KLF4 and other tested genes, in conjunction with overexpression of c-MYC in Burkitt lymphoma patients may be associated with high mitotic rate and more aggressive clinical behavior in this tumor. Activity of the reprogramming factors in both tumor cells and iPS cells may shed light on the origin of tumor stem cells.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr LB-166.
Serial RT-PCR detection of circulating tumour cells as a marker of disease progression in patients with malignant melanoma
Authors: P. A. Ascierto, M. Budroni, A. Cossu, S. Scala, E. Simeone, P. Giuliano, S. M. Satriano, C. Caracò, M. Casula, G. Palmieri
Journal: Journal of Clinical Oncology (2006)

18009 Background: Detection of circulating malignant cells (CMCs) through a reverse transcriptase-polymerase chain reaction (RT-PCR) assay seems to be a demonstration of systemic disease. We here evaluated the prognostic role of RT-PCR assays in serially-taken peripheral blood samples from patients with malignant melanoma (MM). Methods: One hundred forty-nine melanoma patients with disease stage ranging from I to III were consecutively collected in 1997. A multi-marker RT-PCR assay was used on peripheral blood samples obtained at time of diagnosis and every 6 months during the first two years of follow-up (total: 5 samples). Univariate and multivariate analyses were performed after 83 months of median follow-up. Results: Detection of at least one circulating mRNA marker was considered a signal of the presence of CMC (referred to as PCR-positive assay). A significant correlation was found between the rate of recurrences and the increasing number of PCR-positive assays (P = 0.007). Presence of CMC in a high number (≥2) of analysed blood samples was significantly correlated with a poor clinical outcome (disease-free survival: P = 0.019; overall survival: P = 0.034). Multivariate analysis revealed that presence of a PCR-positive status does play a role as independent prognostic factors for overall survival in melanoma patients, adding precision to the predictive power of the disease stage. Conclusions: Our findings indicated that serial RT-PCR assay may identify a high risk subset of melanoma patients with occult cancer cells constantly detected in blood circulation. Prolonged presence of CMCs seems to act as a surrogate marker of disease progression or a sign of more aggressive disease. No significant financial relationships to disclose.
Abstract 14423: Outcomes of Carotid Artery Stenting for Recurrent Carotid Artery Restenosis Following Prior Ipsilateral Carotid Artery Endarterectomy or Stenting
Authors: Brian Hynes, Nicholas J Ruggiero, Kevin F Kennedy, Kenneth Rosenfield, Joseph M Garasic
Journal: Circulation (2011)

Background: Restenosis occurs in 5-15% of patients who undergo carotid artery endarterectomy (CEA) or stenting (CAS). Recurrent stenosis can be treated with CAS; however, outcomes of this approach ...
Subdiaphragmatic Hodgkin's disease: laparotomy and treatment results in 49 patients.
Authors: M H Leibenhaut, R T Hoppe, A Varghese, S A Rosenberg
Journal: Journal of Clinical Oncology (1987)

The clinical records of 1,616 patients with previously untreated Hodgkin's disease were reviewed. Forty-nine of these patients (3%) presented with disease limited to sites below the diaphragm and underwent laparotomy as part of their staging evaluation. The clinical and histological characteristics of this group of patients with subdiaphragmatic Hodgkin's disease are compared with those who presented with supradiaphragmatic disease. Splenectomy in 47 patients revealed splenic involvement in 16 (39%), and bulky splenic involvement (more than five gross nodules) in ten (24%). The final pathological stage (PS) distribution was PS I = 8, PS II = 37, PS IV = 4. No clinical stage (CS) IA patients and only two of 20 patients with negative paraaortic nodes on lymphogram had splenic involvement in contrast to eight of nine CS IIB patients. Freedom from relapse and survival were similar to patients with equivalent stage supradiaphragmatic disease. Splenic involvement and bulky splenic involvement were associated with a significantly decreased survival. Twelve out of 44 PS IA to IIB patients relapsed. In eight of these 12 patients, relapse was limited to sites above the diaphragm and another two patients relapsed both above and below the diaphragm. Patients who received total lymphoid irradiation were less likely to relapse above the diaphragm than patients who received no supradiaphragmatic irradiation. We recommend that CS IA and IIA patients with subdiaphragmatic disease undergo staging laparotomy and receive supradiaphragmatic irradiation as part of their treatment. Laparotomy may not be necessary for CS IIB patients who are at high risk for splenic disease if chemotherapy is planned as part of their treatment program.