tbuckley/cabot-search huggingface dataset:
Safety and efficacy of repeated anti-CEA radioimmunotherapy (RAIT) with 131I-labetuzumab post salvage resection of colorectal liver metastases
Authors: T. Liersch, J. Meller, T. Lorf, C. Sahlmann, M. Niessner, C. Langer, B. M. Ghadimi, W. A. Wegener, H. Becker, D. M. Goldenberg
Journal: Journal of Clinical Oncology (2007)

14507 Background: As shown recently (JCO 2005; 23:6763–70), a single application of RAIT improved both, median overall survival (OS), and 5-year survival rates of colorectal cancer (CRC) patients (pts) post salvage resection of liver metastases (LM) compared to controls without RAIT (P=0.004). In an ongoing phase II trial we are evaluating the safety and efficacy of repeated RAIT at doses of 2x 40–50 mCi/m 2 (3 mos apart) post salvage resection of LM. Methods: To date, 26 pts (8x f, 18x m; age: 63 ± 9 ys) who underwent surgery for CRC-LM have received the first dose of 131I-labetuzumab (Immunomedics, In., NJ, USA), a humanized monoclonal antibody against CEA, within 2 months of LM surgery. Three months after the first RAIT, a second infusion of 40–50 mCi/m 2 has been applied to all pts after completion of standardized re-staging procedures. Results: The primary tumor sites were 17 colonic and 9 rectal cancers; primary tumor stages were 5x UICC-II, 7x UICC-III, 14x UICC-IV. 13 pts received adjuvant therapy. In 11 pts preoperative chemotherapy (FOLFOX or FOLFIRI) was given to achieve resectability of bilobular LM. After resection of LM (y)mTNM tumor stages were 1x mTNM-I, 6x mTNM-II, 6x mTNM-III and 4x mTNM-IV, respectively. After first RAIT, hematologic Grade 3 and 4, toxicity (WBC/platelet count) occurred in 8/14 and 5/3 pts, respectively. No cumulative toxicity was seen after repeated RAIT, with complete bone marrow recovery observed in all cases so far. To date, all pts are alive. Of the total, 17 pts received RAIT with adjuvant intention (as classified by FDG-PET and CT scans at pre-RAIT re-staging). In these, DFS was 70% post salvage resection of LM during ongoing follow-up of 15 months (median; range: 4–23 mos). As of Dec. 20, 2006, cancer recurrence was detected in 5/17 pts (3x pulmonary, 1x intrahepatic, 1x both) and in 4 pts R0-resection of distant metastases was done. 1 patient with pulmonary and intrahepatic relapses receives polychemotherapy with palliative intention. The pts‘ compliance to repeated RAIT has been 100%. Conclusion: RAIT re-treatment to date appears to be safe, feasible, and well accepted. Extended follow-up of the encouraging survival data will be presented. No significant financial relationships to disclose.
GW26-e5451 Real world experience of Primary PCI in 1000 STEMI patients in Indian scenario at a tertiary care center
Authors: Rajasekhar Durgaprasad, Vanajakshamma Velam, Vamsidhar Akkulagari, Boochi Babu Mannuva, Latheef Kasala
Journal: Journal of the American College of Cardiology (2015)
Effect of cancer cachexia on treatment toxicity in metastatic colorectal cancer patients: Results of a prospective multicenter study.
Authors: Maximilien Barret, Cecile Dalban, Julien Taïeb, David Malka, Touraj Mansourbakht, Ewa Latko, Sami Antoun
Journal: Journal of Clinical Oncology (2012)

9026^ Background: Malnutrition reduces tolerance to treatment and survival in numerous cancers, including metastatic colorectal cancer (mCRC). Previous studies have shown that chemotherapy toxicity may be linked to sarcopenia. We evaluated the effect of sarcopenia on chemotherapy toxicity among mCRC patients. Methods: In this prospective, cross-sectional, multicenter study, oncological and nutritional data were collected in all consecutive mCRC patients between March 7th and March 20th 2005 in three hospitals. Computed tomography (CT) images were analysed using Slice-O-Matic software V4.3 (Tomovision) to evaluate cross-sectional areas (cm2) of muscle tissue (MT), visceral and subcutaneous adipose tissue (VAT and SAT). The 3rd lumbar vertebra (L3) was chosen as a reference, since L3 and whole-body measurements are linearly related. Indexed on height, MT, VAT and SAT (cm2/m2), were computed and described, after stratification on sex. In accord with the literature, sarcopenia was defined as MT &lt;55 cm2/m2 for men and &lt;39 cm2/m2 for women. Images were obtained within one month of clinical evaluation. Toxicities were evaluated according to the NCI-CTC, version 3.0, in the two months following clinical evaluation. Results: 53 mCRC patients (72% men (M)), participated in the study. According to body mass index (BMI) only 7% of female patients (F) and 3% M were malnourished (BMI&lt;17 kg/m²), and 93% F and 97% M were of normal weight or overweight (BMI&gt; 25kg/m²). These results are to be compared to the 38% (F) and 82% (M) of patients with sarcopenia. Grade 3-4 toxicities were observed in 28% of the cases, with neurotoxicity in 6%, diarrhea 2%, anemia 2%, neutropenia 9%, and nausea and vomiting 6%. In multivariate analysis including age, sex, BMI, sarcopenia, SAT and VAT, the only factor associated with grade 3-4 toxicity was sarcopenia (OR= 13.55 95% CI [1.08;169.31], p=0.043). Conclusions: In mCRC patients undergoing chemotherapy, low muscle tissue was much more frequently observed (68%) than “visible” malnutrition (4%). Despite the small number of patients included in our study, we showed that sarcopenia was associated with severe chemotherapy toxicity in mCRC.
Efficacy of NEDD8 Pathway Inhibition in Preclinical Models of Poorly Differentiated, Clinically Aggressive Colorectal Cancer
Authors: Gabriele Picco, Consalvo Petti, Francesco Sassi, Katia Grillone, Giorgia Migliardi, Teresa Rossi, Claudio Isella, Federica Di Nicolantonio, Ivana Sarotto, Anna Sapino, Alberto Bardelli, Livio Trusolino, Andrea Bertotti, Enzo Medico
Journal: JNCI Journal of the National Cancer Institute (2016)

The NEDD8 conjugation pathway modulates the ubiquitination and activity of a wide range of intracellular proteins, and its blockade by pevonedistat is emerging as a promising therapeutic approach in various cancer settings. However, systematic characterization of pevonedistat efficacy in specific tumor types and definition of response predictors are still missing.We investigated in vitro sensitivity to pevonedistat in 122 colorectal cancer (CRC) cell lines by an ATP-based proliferation assay and evaluated apoptosis and DNA content by flow cytometry. Associations between pevonedistat sensitivity and CRC molecular features were assessed by Student's t test. A 184-gene transcriptional predictor was generated in cell lines and applied to 87 metastatic CRC samples for which patient-derived xenografts (PDXs) were available. In vivo reponse to pevonedistat was assessed in PDX models (≥5 mice per group). All statistical tests were two-sided.Sixteen (13.1%) cell lines displayed a marked response to pevonedistat, featuring DNA re-replication, proliferative block, and increased apoptosis. Pevonedistat sensitivity did not statistically significantly correlate with microsatellite instability or mutations in KRAS or BRAF and was functionally associated with low EGFR pathway activity. While ineffective on predicted resistant PDXs, in vivo administration of pevonedistat statistically significantly impaired growth of five out of six predicted sensitive models (P < .01). In samples from CRC patients, transcriptional prediction of pevonedistat sensitivity was associated with poor prognosis after surgery (hazard ratio [HR] = 2.49, 95% confidence interval [CI] = 1.34 to 4.62, P = .003) and early progression under cetuximab treatment (HR = 3.59, 95% CI = 1.60 to 8.04, P < .001). Histological and immunohistochemical analyses revealed that the pevonedistat sensitivity signature captures transcriptional traits of poor differentiation and high-grade mucinous adenocarcinoma.These results highlight NEDD8-pathway inhibition by pevonedistat as a potentially effective treatment for poorly differentiated, clinically aggressive CRC.
Transglutaminase Interaction with α6/β4-Integrin Stimulates YAP1-Dependent ΔNp63α Stabilization and Leads to Enhanced Cancer Stem Cell Survival and Tumor Formation
Authors: Matthew L. Fisher, Candace Kerr, Gautam Adhikary, Dan Grun, Wen Xu, Jeffrey W. Keillor, Richard L. Eckert
Journal: Cancer Research (2016)

Transglutaminase 2 (TG2) expression is required for epidermal squamous cell carcinoma cancer stem cell survival. However, the molecular signaling mechanisms triggered by TG2 that mediate this survival action are not well understood. Here we show that TG2 is constitutively expressed in ECS cells, where it interacts with α6/β4 integrin to stimulate FAK and Src signaling, leading to PI3K activation of phosphoinositide-dependent kinase 1 (PDK1). PDK1 inhibits Hippo signaling, leading to enhanced nuclear accumulation of YAP1, which interacted with and stabilized ΔNp63α to enhance epidermal squamous cell carcinoma spheroid formation, invasion, and migration. Overall, these findings suggest that constitutive TG2 expression results in stabilization of ΔNp63α, leading to maintenance of cancer stem cell properties and enhanced tumor formation. Cancer Res; 76(24); 7265-76. ©2016 AACR.
Phase I trial of sorafenib in high-risk hepatocellular carcinoma (HCC) patients after liver transplantation (LT).
Authors: A. B. Siegel, S. X. Hsu, K. D. Becker, S. Anderson, S. Clark-Garvey, R. Hidalgo, D. Tsushima, I. Matushansky, J. Emond, R. S. Brown
Journal: Journal of Clinical Oncology (2010)

TPS211 Background: Liver transplantation offers long-term survival for 75-80% of HCC patients who fall within the Milan criteria. For those who fall outside these criteria, rates of recurrence are much higher. About a third of HCC patients are transplanted outside Milan criteria at our institution. There are no known treatments that decrease risk of recurrence post-transplant. Sorafenib is a tyrosine kinase inhibitor which targets several pathways, including VEGFR2-3, PDGFR and Raf. It was the first drug approved for the treatment of advanced HCC in the United States. We began a phase I dose escalation study of sorafenib in high-risk HCC patients after liver transplantation at our center to assess safety in preparation for a larger study to evaluate efficacy in this population. Methods: Eligible subjects include patients with biopsy-proven HCC outside Milan criteria, those with poorly differentiated tumors, or with microvascular invasion at explant. We are using a standard phase I dose-escalation design, beginning drug between 4 and 12 weeks after liver transplantation, with a planned duration of treatment of 6 months. Cohort dosages are as follows: 1) 200 mg q day, 2) 200 mg BID, 3) 200 mg/400 mg, and 4) 400 mg BID. Correlative studies include circulating endothelial cells (CECs) and plasma angiogenic and inflammatory markers which are being collected prior to treatment, at 1 month, and at recurrence in a subset of patients as possible predictive and prognostic biomarkers. CECs are assayed by mixing whole blood with a ferrofluid of magnetic nanoparticles coated with antibodies to CD146, which captures endothelial cells. Cells are then stained with CD105, CD45, and the nuclear stain DAPI. CECs are identified as CD105(+), DAPI(+), and CD45(-). Plasma markers include VEGF, VEGFR2, and IL- 6. We have enrolled 4 patients out of a planned enrollment of 24 patients. We are planning a larger phase II feasibility study though the Southwest Oncology Group (SWOG). Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bayer Investigator's Meeting Research project
Surgery versus conservative management for recurrent and ongoing left-sided diverticulitis (DIRECT trial): an open-label, multicentre, randomised controlled trial
Authors: Bryan J M van de Wall, Marguerite A W Stam, Werner A Draaisma, R Stellato, Willem A Bemelman, Marja A Boermeester, Ivo A M J Broeders, Eric J Belgers, Boudewijn R Toorenvliet, Hubert A Prins, Esther C J Consten
Journal: The Lancet. Gastroenterology & hepatology (2016)
Radiographic and immunologic responses to adjuvant immunotherapy for malignant gliomas
Authors: P. Z. New, D. Baskin, T. Trask, R. Cavaliere, A. R. Chaudhury, S. Bell, L. K. Aguilar, E. Aguilar-Cordova, A. Chiocca, K. Wong
Journal: Journal of Clinical Oncology (2008)

2039 Background: The invasive nature of malignant gliomas leads to a high rate of recurrence. Recruitment of the immune system to eradicate residual tumor may provide a significant outcome improvement. AdV-tk, an adenoviral vector containing the Herpes virus thymidine-kinase gene (GliAtak, Advantagene) plus prodrug has shown promise as an immuno-stimulatory adjuvant to standard therapies. The mechanisms involve tumor cytotoxicity combined with local elicitation of danger signals, recruitment and activation of antigen presenting cells and stimulation of systemic antitumor T- cell immunity. Methods: Patients with newly diagnosed malignant glioma received one of three dose levels of AdV-tk (3×1010, 1×1011 and 3×1011 vector particles) delivered to tumor cells via tumor bed injection followed by valacyclovir 2gm TID×14d. Radiation began within 7 days and temozolomide was allowed after prodrug completion. Results: The study enrolled 3 patients in each of the first two dose levels and 6 in the third. Tumors were classified as WHO grade IV (GBM) in 10 patients and anaplastic astrocytoma in two. Possibly related toxicity included transient elevation of liver transaminase, creatinine and fever. There were no significant related delays or interruptions in radiation or temozolomide. Five patients are alive 12–21 months after treatment. Significant intratumoral T-cell and macrophage infiltrate was seen in two patients who underwent re-resection at 30 and 36 weeks, suggesting a treatment induced antitumor response. One GBM patient, with persistent enhancement and FLAIR signal resolving slowly over 9 months is progression-free >20 months after treatment. Three patients have persistent enhancement and FLAIR signals but no progression for >12 months. Radiation and immune effects may confound interpretation of conventional imaging. Perfusion MRI was used in two of these three patients in an attempt to differentiate tumor progression from treatment effects. Conclusions: AdV-tk can be safely combined with surgery and radio-chemotherapy in patients with newly diagnosed malignant gliomas. Novel imaging techniques may help differentiate tumor progression from inflammation after radio-immunotherapy. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Advantagene Advantagene
Acquired resistance to anti-PD1 therapy: checkmate to checkpoint blockade?
Authors: Jake S. O’Donnell, Mark J. Smyth, Michele W. L. Teng
Journal: Genome Medicine (2016)

Anti-programmed cell death 1 (PD1) immunotherapies are among the most effective anti-cancer immunotherapies available; however, a large number of patients present with or develop resistance to them. Unfortunately, very little is known regarding the mechanisms of resistance to such therapies. A recent study sought to identify mutations associated with resistance to anti-PD1 therapy. Results from this study demonstrated that mutations which affected the sensitivity of tumor cells to T-cell-derived interferons, and mutations limiting tumor-cell antigen presentation, could cause acquired resistance. These findings have significant implications for understanding the mechanisms by which anti-PD1 therapies exert their efficacy, comprehending why and how some patients acquire resistance over time, and ultimately guiding the development of combination therapies designed to overcome, or potentially prevent, the development of acquired immunotherapeutic resistance.
Influence of atrial fibrillation on post‐discharge natriuretic peptide trajectory and clinical outcomes among patients hospitalized for heart failure: insights from the <scp>ASTRONAUT</scp> trial
Authors: Stephen J. Greene, Gregg C. Fonarow, Scott D. Solomon, Haris P. Subacius, Andrew P. Ambrosy, Muthiah Vaduganathan, Aldo P. Maggioni, Michael Böhm, Eldrin F. Lewis, Faiez Zannad, Javed Butler, Mihai Gheorghiade
Journal: European Journal of Heart Failure (2016)
Abstract 14720: Firefighters Have the Highest Risk for Heart Disease Among Emergency Personnel
Authors: Kelsey A Moody, Tracey Matthews, Richard Wood, Laurel A Ayvazian, Erin A Woodbury, Molly Gile, Heidi Szalai, Quinn R Pack, Samuel Headley
Journal: Circulation (2015)

Introduction: Prior studies have shown obesity, lower activity levels and increased stress among emergency personnel, yet it is unclear if the specific sub-type of emergency personnel impacts stress levels and physical activity (PA). The purpose of this study was to compare emergency personnel sub-types for risk of heart disease and compare on and off duty PA and stress levels. Hypothesis: We hypothesized that there would be differences in cardiac risk factors, exercise behaviors, and salivary cortisol by type of emergency responders and would be different when on/off duty. Methods: We recruited 37 male emergency personnel workers (12 paramedics, 12 police officers and 13 firefighters, ages 20-40) who then underwent three non-sequential days of testing. We measured body composition, lipids, blood pressure, and peak VO2 with a standard Bruce treadmill protocol and calculated Framingham Risk Scores (FRS) on the first day of testing. Participants then wore an accelerometer and measured AM and PM salivary cortisol on and off duty. Results: Contrary to our hypothesis, PA levels did not differ between on and off duty. Firefighters expended significantly more kcals per day and took more steps per day compared to paramedics (p &lt; 0.05). Cortisol concentration was significantly higher AM vs. PM on duty (p &lt; 0.05); although off duty cortisol remained elevated. No significance was found between off duty values. Firefighters’ FRS was significantly higher than paramedics (p &lt; 0.05). See Table. Conclusion: In conclusion, although firefighters were more active than police and paramedics, they had a higher FRS. Among all emergency personnel types, cortisol concentrations showed a prolonged stress response in the emergency personnel population suggesting a sustained off duty stress response for unclear reasons. These finding suggest that firefighters should focus on decreasing cardiac risk factors and interventions are needed to reduce emergency personnel off duty stress.
Effect of a synthetic peroxisome proliferator-activated receptor-gamma (PPARγ) ligand on breast cancer cells
Authors: H. Youn, B. Lee, S. Jung
Journal: Journal of Clinical Oncology (2009)

e14638 Background: Peroxisome proliferator-activated receptor-gamma (PPARγ) ligands have been identified as a potential source of therapy for human cancers. And, it is reported that PPAR-γ ligands could serve as negative regulators of breast cancer development and progression, but their mechanism is still unknown. The purpose of this study was to determine whether the PPAR- γ ligand induces cell cycle arrest and apoptosis of MDA-MB-231(ERα-negative) and MCF-7(ERα-positive) breast cancer cell. Methods: The effect of PPAR-γ ligands on the cell viability of breast cancer cells was determined using mitochondrial tetrazolium(MTT) assay. The cell cycle distribution and apoptosis induction were evaluated by using the flow cytometry. The expression of apoptosis-related proteins were measured with Western blot analysis. Results: The treatment of MDA-MB- 231 cell with PPAR-γ ligand, troglitazone was shown to induce cell cycle G 1 arrest and induction of apoptosis. Moreover, troglitazone treatment, applied in a dose-dependent manner, caused a marked decrease in phosphorylated retinoblastoma(pRb), cyclin D 1 , D 2 , D 3 , cyclin dependent kinase(Cdk) 2, 4, and 6 expression as well as a significant increase in Cdk inhibitor, p21 and p27. Troglitazone showed antiproliferative effect on MCF-7 cell with tamoxifen, respectively and synergically. Troglitazone and tamoxifen could induce G 1 arrest and apoptosis of MCF-7 cell, through upregulation of Bax and downregulation of Bcl-2 and cyclin D 1 . Conclusions: PPAR-γ ligand, troglitazone induces cell cycle arrest and apoptosis of MDA-MB-231 cell and increases the sensitivity of anti-hormonal therapy in MCF-7 cell. These results suggest that troglitazone has anticancer effect on both ERα-negative and positive breast cancer cells. No significant financial relationships to disclose.
A Pharmacogenetic Study of the NCIC CTG Clinical Trial My.10: Single Nucleotide Polymorphisms, Prognosis, and Predicting Benefit from IMiD® Compound Maintenance Therapy Following Autologous Stem Cell Transplant for Multiple Myeloma
Authors: Ming Han, Alli Murugesan, Nizar J Bahlis, Kevin Song, Darrell White, Christine Chen, Matthew D. Seftel, Kang Howsen-Jan, Donna Reece, Keith Stewart, Yagang Xie, Annette E Hay, Lois Shepherd, Bingshu E Chen, Marina Djurfeldt, Tony Reiman
Journal: Blood (2015)
Hematopoietic Stem Cell Transplantation for Patients with β-Thalassemia Major Underwent Pre-Transplant Splenectomy
Authors: Yuelin He, Xuedong Wu, Yongsheng Ruan, Zhiyong Peng, Xiaoqin Feng, Jianyun Liao, Huaying Liu, Wenfeng Xu, Na Li, Chunfu Li
Journal: Blood (2014)
Intrapleural combination bevacizumab with cisplatin therapy for non-small cell lung cancer caused by non-small cell lung cancer.
Authors: Nan Du, Hui Zhao, Haibin Wang, Xiaosong Li, Junxun Ma, Zhongyi Fan
Journal: Journal of Clinical Oncology (2012)

7036 Background: Malignant pleural effusion (MPE) is a common complicate of advanced non-small cell lung cancer (NSCLC). Bevacizumab, a humanized monoclonal antibody to VEGF, has been shown to be efficient in suppressing the pleural fluid accumulation; however, it has not been reported that whether bevacizumab can be used intrapleurally for the treatment of MPE. The present study is to evaluate the efficacy and safety of combined intrapleural therapy with bevacizumab and cisplatin, an antineoplastic agent, in controlling MPE. Methods: A total of 65 NSCLC patients with MPE were randomly assigned to one of two groups: intrapleural bevacizumab (300mg) with cisplatin (60mg) therapy (n=35) and intrapleural cisplatin (60mg) therapy (n=30). Results: The curative efficacy following combination or cisplatin mono therapy were 85.71% and 56.67%, respectively, being combination therapy group (p&lt;0.05) is significantly higher. In addition, the combination therapy showed a higher efficacy in the patients with VEGF positive (p&lt;0.01). Among the 25 cases that showed initial resistance to chemotherapy, 22 responded well to the combination therapy. Furthermore, combined bevacizumab with cisplatin therapy significantly reduced the VEGF expression, as shown by quantitative RT-PCR. All procedures were well tolerated by the patients, with wwwno severe side effect detected. Conclusions: Intrapleural combined bevacizumab with cisplatin therapy was effective and safe in managing MPE caused by NSCLC; the expression level of VEGF in MPE can be a prognostic marker for bevacizumab therapy.
GW26-e0204 Variants of Mitochondrial Genome in Patients with Subclinical Atherosclerosis
Authors: Igor A. Sobenin, Andrey V. Zhelankin, Varvara A. Orekhova, Zukhra B. Khasanova, Vasily V. Synyov, Anton Y. Postnov, Alexander N. Orekhov
Journal: Journal of the American College of Cardiology (2015)
Low and disparate seroprotection after pentavalent childhood vaccination in the Lao People's Democratic Republic: a cross-sectional study
Authors: K. Evdokimov, K. Sayasinh, P. Nouanthong, K. Vilivong, B. Samountry, D. Phonekeo, M. Strobel, F. Haegeman, P. Heimann, C.P. Muller, A.P. Black
Journal: Clinical Microbiology and Infection (2016)
A Novel Splice Site Variant of hOCT-1 and Response to Imatinib.
Authors: Jacob Grinfeld, Juan M Alonso-Dominguez, Mary Alikian, Mikel Valgañón, Georgios Nteliopoulos, Deborah L. White, David Marin, Corinne Hedgley, Stephen O'Brien, Richard E. Clark, Richard M Szydlo, Jane Apperley, John M Goldman, Letizia Foroni, Gareth Gerrard
Journal: Blood (2012)