tbuckley/cabot-search huggingface dataset:
Abstract 17577: Peripheral Blood Gene Expression in Acute Coronary Syndrome Reflects Acute Inflammatory Responses and Correlates With Residual Inflammation at Follow-up
Authors: Maarten Vanhaverbeke, Ambra Pastori, Heinrich J Huber, Thibault Petit, Sander Trenson, Tom Adriaenssens, Johan Bennett, Christophe Dubois, Walter Desmet, Stefan Janssens, Peter Sinnaeve
Journal: Circulation (2015)

Introduction: Previous research showed that peripheral blood gene expression profiles correlate with the extent of coronary artery disease (CAD) in stable non-diabetic patients. It remains unknown how these expression profiles change during an acute coronary syndrome (ACS), and whether they relate to residual inflammation at 30-days follow-up. Methods: Peripheral blood samples were prospectively collected from 34 unselected ACS patients (mean age 62 years, 20 STEMI and 14 NSTEMI) on admission and after 30 days. Total RNA was extracted from whole blood at both time points and micro-array analysis was performed (Affymetrix). The results were validated with qRT-PCR and correlated to clinical characteristics and biomarkers. Results: On admission, 170 inflammatory transcripts were differentially expressed when compared to 30 days after the event. Pathway analysis revealed IL-1ß and TNF-α as common upstream regulators of these transcripts. From the top 10 genes, we selected 4 significantly upregulated genes on admission for qRT-PCR validation: CLEC4E (fold change 2.2, p &lt;0.001), FKBP5 (fold change 2.3, p &lt;0.001), IL18RAP (fold change 1.6, p =0.002) and the inflammasome-related NLRC4 (fold change 1.8, p &lt;0.001). These findings were consistent in STEMI and NSTEMI. The gene expression levels on admission were inversely related to hsCRP levels at 30 days. Patients with a high gene expression score on admission had a mean hsCRP of 0.56±0.11mg/l at 30-day follow-up, vs. 2.44±0.75mg/l in patients with a low gene expression score ( p =0.035, figure 1). This difference was independent of peak troponin T or peak CRP. Conclusion: Peripheral blood gene expression profiles reflect acute inflammatory responses in ACS. Lower baseline gene expression levels, but not infarct size or peak CRP, were associated with higher hsCRP at 30 days, an important marker of residual cardiovascular risk. Whether these expression profiles correlate with outcome needs further investigation.
T(X;14)(p11.4;q32.33) Is Recurrent In Marginal Zone Lymphoma and Upregulates GPR34
Authors: Iwona Wlodarska, Julio Finalet Ferreiro, Thomas Tousseyn, Helena Urbankova, Lucienne Michaux, Laurence de Leval, Daan Dierickx, Pascal Wolter, Xavier Sagaert, Peter Vandenberghe, Christiane De Wolf-Peeters, Mathijs Baens
Journal: Blood (2011)
P0762 : Non-RNA testing among hepatitis C virus antibody-positive patients in a national public health insurance care system: Prevalence, characteristics and predictive factors
Authors: D.E. Morales Arraez, A. Alonso, F. Diaz-Flores, J.A. Garcia Dopico, A. de Vera, E. Quintero, M. Hernandez Guerra
Journal: Journal of Hepatology (2015)
Brivanib (BMS-582664) in advanced solid tumors (AST): Results of a phase II randomized discontinuation trial (RDT).
Authors: M. J. Ratain, G. K. Schwartz, A. M. Oza, C. M. Rudin, S. B. Kaye, M. J. De Jonge, D. Khayat, A. Awada, M. B. Sawyer, J. C. Obel, J. Medioni, T. R. J. Evans, J. De Greve, P. M. Soetekouw, J. Baurain, P. J. O'Dwyer, C. Hartman, V. Poulart, I. B. Walters
Journal: Journal of Clinical Oncology (2011)

3079 Background: Brivanib (B) is an oral once daily selective dual inhibitor of FGF and VEGF signaling currently in phase III development for advanced hepatocellular carcinoma and colorectal cancer. An adaptive RDT was performed to assess therapeutic activity in other AST. Methods: Pts aged ≥18 y with unresectable AST and no other treatment options received open label fixed dose B 800 mg qd for a 12-wk lead-in period, after which they were assessed by CT/MRI. Pts with RECIST response continued on open-label B, those with progressive disease (PD) went off study, and those with stable disease (SD) were randomized 1:1 to B or placebo (P), stratified by FGF2 expression (IHC + or -), until PD or unacceptable toxicity. Steering Committee review of initial open-label data was used to stop enrollment in tumor cohorts with activity judged insufficient to justify expansion. The trial specified 70 randomized pts needed to assess the primary endpoint of improved PFS with a HR of 0.5; secondary endpoints included safety, ORR, duration of response, DCR, PK/PD, and exploratory biomarkers. Results: A total of 396 pts with 5 AST types received study treatment. Early evidence of activity prompted expansion of the soft tissue sarcoma (STS) cohort to 251 pts to achieve 76 randomized, showing prolonged PFS for B vs P (HR 0.64, 90% CI 0.41–0.98; P=.09). Single agent B activity in FGF2+ pancreatic, gastric, bladder, and NSLC was judged insufficient to justify expansion of these cohorts, allowing closure decisions to be made with ≤42 pts. Common AEs were as expected; grade 3-4 AEs ≥5% were hypertension, fatigue, dyspnea, and abdominal pain. Conclusions: The adaptive RDT design conserved pt resources by efficiently identifying tumor types with encouraging activity and demonstrated a potential benefit in pts with STS. Common AEs associated with B monotherapy were as expected across tumor types. Biomarker exploration with potential for enrichment continues; breast and ovarian cohorts have been added to the trial. Tumor type N ≥ 2 prior regimens, % FGF2+, %* Status at 12 wk, % PR SD Sarcoma 251 52 65 3 27 NSCLC 42 93 79 0 24 Pancreatic 38 66 79 0 13 Gastric 34 71 97 9 9 Bladder 31 52 88 0 16 *Assessable patients
A potential source of new chemopreventive agent for bladder cancer from Ganoderma lucidum
Authors: John W. M. Yuen, Mayur Danny I. Gohel
Journal: Cancer Research (2006)

4805  Introduction: Although tumor resection is effective for treating transitional cell carcinoma (TCC) of the urinary bladder, the recurrence rate remains high. A powerful chemopreventive agent is demanded for people at risk. Human uroepithelial cells (HUC), the prime target of most known bladder carcinogen, is able to become tumorigenic when immortalized with Simian virus 40. The anti-cancer effects of defined extracts from Ganoderma lucidum (Lingzhi) for antioxidant / oxidant and cytotoxic mechanisms were studied with pre-malignant SV40-HUC-PC cell line. Brief Methodology: The SV40-HUC-PC cells were incubated with 4-aminobiphenyl (4-ABP) and/or extracts of Lingzhi as intervention groups. Cell culture media of each study group were collected at 0, 2, 4, 6, 12, 24, and 48 hours, to measure the total antioxidant power (FRAP value), 1,1-Diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity, and hydrogen peroxide (H2O2) concentration. Moreover, cytotoxicity of cells in each group was assessed at 24 and 48 hours incubation, and 72 hours post-incubation, using Lactate Dehydrogenase (LDH) and/or trypan blue staining method. Results and Discussion: Compared to the control group, oxidative stress was induced by 4-ABP, while antioxidant activities were enhanced by Lingzhi extracts, during the course of HUC cultures. The FRAP total antioxidant power was maintained at a steady level when the cells were incubated with ABP together with either water or ethanol extract of Lingzhi, indicating the potential protection of the cells from oxidative attacks. Interestingly, at non-cytotoxic levels, the ethanol extract of Lingzhi (LE) killed 90% and 10% of the pre-malignant cells with or without 4-ABP at 48 hours respectively, whereas the water extracts did not. Cells incubated for 24 hours with 4-ABP/LE were washed and successively fed with media containing LE, and almost all the cells were killed within 72 hours, in addition to morphological changes in the cells. The cell growth was inhibited by LE in the absence of 4-ABP for up to at least 3 days. Conclusion: Conclusively, the results indicated that ethanol extract of Lingzhi possesses anti-cancer effects in the three aspects, which are (1) protecting HUC from potential oxidative attacks during carcinogenesis; (2) inhibiting the growth of pre-malignant SV40-HUC-PC; and (3) eliminating adverse cells under carcinogenic stress. Lingzhi is a potential source of new chemopreventive agent for bladder cancer. The underlying mechanisms regarding cell signaling transduction are being investigated.
ASSESSMENT OF TUMOR GENOTYPES IN METASTATIC COLORECTAL CANCER (MCRC): MUTATIONS BEYOND KRAS CODONS 12 AND 13 AS PREDICTIVE BIOMARKERS OF RESPONSE TO PANITUMUMAB (PMAB) IN A RANDOMIZED, PHASE 3 STUDY
Authors: Marc Peeters, Kelly S Oliner, Salvatore Siena, Eric Van Cutsem, Jing Huang, Yves Humblet, Jean-Luc Van Laethem, Thierry Andre, Jeffery Wiezorek, Scott D Patterson
Journal: Annals of Oncology (2011)
Gemcitabine and cisplatin with or without sorafenib in urothelial carcinoma (AUO-AB 31/05).
Authors: S. Krege, H. Rexer, F. vom Dorp, P. Albers, P. De Geeter, T. Klotz
Journal: Journal of Clinical Oncology (2010)

4574 Background: This is a prospective randomised double-blind phase II trial to compare gemcitabine and cisplatin with or without sorafenib in histologically verified locally advanced or metastasized urothelial carcinoma. Methods: Patients were randomised from 10/06 until 10/09. Included were patients with ECOG 0-1 performance status. Brain metastases and prior systemic chemotherapy were exclusion criteria. Patients received 1250mg/qm gemcitabine iv on day 1 and 8, 70mg/qm cisplatin iv on day 2 and 2x400mg sorafenib or placebo po daily on day 3-21 until progression or unacceptable toxicity. Patients were assessed for response using RECIST after every 2 courses of therapy. Progression-free survival (PFS) was the primary endpoint. Secondary endpoints included objective response rate (ORR), time to progression (TTP), overall survival (OS) and toxicity Results: This analysis includes toxicity data of 85 patients, 44 patients received placebo (arm A), 41 sorafenib (arm B). 42% of the patients only received one or two cycles of chemotherapy, 19% up to 4 cycles, 33% up to 6 cycles and 6% up to 8 cycles. There were no significant differences concerning dose reduction of medication or prolonged intervals between cycles within the two arms. Serious adverse events were observed in 19 (43%) and 19 (46%) patients; Grade 3/4 toxicity occurred in 19 (43%) and 20 (49%) patients (arm A vs arm B). Myelosuppression was identical in arm A and B (grade 3/4 leucocythopenia 6/6; thrombocythopenia 5/5 and anemia 3/3). 2 patients in arm A and one in arm B suffered from severe infection. Grade 3/4 nausea and emesis occurred in six patients in arm A and three patients in arm B. Severe diarrhea (n=3), dyspnoe (n=2), cardiac dysfunction (n=1) and intracerebral bleeding (n=1) were only observed in arm B. Data about response rate, time to progression, progression free survival and overall survival will be presented. Conclusions: There were no major differences in safety between the sorafenib and placebo arm with the exceptions mentioned above. No significant financial relationships to disclose.
Study of different mutations in chronic myeloid leukemia in India and their co-relation with drug resistance.
Authors: Priti Mitra, Swati Dasgupta, Chinmay Kumar Basu, Firoj Hossain Gharami, Subrata Mandal, Ashis Mukhopadhyay
Journal: Journal of Clinical Oncology (2013)

7083 Background: Emergence of ABL point mutations is the most frequent cause for imatinib resistance in CML. Aim of our study is to investigate two potential resistance mechanisms i.e.,mutations of BCR-ABL tyrosine kinase domain (TKD) and Additional Chromosomal Abnormalities during TKI treatment in CML. Methods: Karyotyping and BCR-ABL TKD mutation screening are performed in 100 imatinib resistant CML patients who were on imatinib at the time of loss of hematologic response, cytogenetic or molecular response. Imatinib–Resistance Mutation Analysis (Qualitative) were detected by Nested RTPCR and Sanger’s Sequencing. In 100 cases, 34 received escalated imatinib, 34 nilotinib and another 32 dasatinib. Results: In 100 BCR-ABL positive imatinib, nilotinib and dasatinib resistant cases, 11 different BCR-ABL TKD mutations were detected. Analysis revealed no mutations-43 cases, M351T-12 cases, G250E-10 cases, F317L-8 cases, M244V-5 cases, E255K-4 cases, V379I-4 cases, F359V-3 cases, H396R-3 cases, Y253F-3 cases, E355G-3 cases, T315I-2 cases. 11 novel mutations (F317L, G250E, M244V, Y253F, E255K, M351T, F359V, H396R, V379I, E355G, T315I) conferring imatinib resistance, 10 nilotinib–resistant mutations (M244V, F359V, T315I, E355G, G250E) and 8 dasatinib-resistant mutations (H396R, F317L, H396R, T315I, M351T) were seen in our patient population. T315I was found more frequently in cases on dasatinib than on imatinib therapy. Conclusions: T315I which confers resistance to all TKIs was detected only in 2/100 patients who demonstrated loss of response in our population. As compared with other western studies, incidence of T315I mutation was very low in our study. In addition analysis of mutation patterns at baseline may help in stratifying patients for treatment. For cases with TKI resistance, mutation and ACA screening may play role in identifying patients with poorer prognosis. In our practice if nilotinib–resistant mutation was detected, dasatinib was preferred and for dasatinib-resistant mutation, nilotinib was preferred. We are planning for using bosutinib, panotinib and omacetaxine (SC route) in third line therapy in imatinib resistant different mutation positive chronic myeloid leukemia.
Improving therapeutic outcomes and mitigating drug-induced systemic toxicity using noninvasive, targeted focused resonance nanopermeabilization (FORN).
Authors: Meena Augustus, Anjana Rani Nair, Ramanathapuram Venkatasubramaniam Parameswaran, Poonam Patil, Rajah Vijay Kumar
Journal: Journal of Clinical Oncology (2014)

e14013 Background: Focused Resonance Nano-permeabilization (FORN) is a patented process whereby the targeted delivery of chemotherapeutic molecules is enabled by its concurrent use with planned chemotherapy. The whole body device called the CYTOFORN houses a gantry of 864 radiofrequency (RF) guns with specialized near field antennae. In a proof of concept study, drug focusing and delivery was enabled using FORN in a patient with loco-regionally recurrent, metastatic, nasopharyngeal carcinoma (NPC). Methods: Non-ionizing, safe, extraneous-source radio-frequencies (RF) are delivered in the presence of an instantaneous magnetic field, to create temporary, drug molecular weight-specific nano-pores in the cell membrane of target lesions, after administration of chemotherapy. The high frequency RF is timed and delivered to ROIs, to span peak plasma concentrations of infused drugs. Results: FORN enabled chemotherapy-related adverse event evaluation and tumor response based on PERCIST 1.0 reflected improved clinical, anatomical and metabolic outcomes and significantly reduced myelosuppression. Functional Assessment of Chronic Illness Therapies-Head & Neck (FACT-H&N)/Quality of Life (QoL) and Karnofsky pain scores reflected overall patient well-being. Recurrent, loco-regional disease, nodal, hepatic and skeletal metastases showed dramatic response on PET-CT follow up. Conclusions: Concurrent chemo-radiotherapy (CCRT) as a treatment paradigm is the standard of practice in locally advanced nasopharyngeal carcinoma (NPC), followed by varying chemotherapy regimens in relapsed NPC with distant metastases. However, the severe cytotoxicity experienced with these modalities has made patient compliance poor and survival statistics dismal. The role of concurrent chemotherapy with a drug focusing and delivery-enabling technology like FORN can help overcome dose-limiting cytotoxicity and improve therapeutic windows with existing and emerging chemotherapeutic regimens. Providing the QoL that is largely lacking, while positively impacting therapeutic outcomes and progression free survival, fulfills an unmet medical need today.
KRAS and BRAF mutational status as selective criteria for targeted therapy in cholangiocarcinoma.
Authors: G. Brandi, M. Fiorentino, S. Di Girolamo, F. de Rosa, A. Altimari, E. Gruppioni, E. Nobili, F. Grigioni, G. Biasco
Journal: Journal of Clinical Oncology (2010)

e14644 Background: Mutations of KRAS and BRAF genes have been associated with resistance to treatments targeted at EGFR pathway in advanced colorectal cancer and other solid tumors. Cetuximab is currently being tested in advanced biliary tract cancer, with encouraging preliminary results although definitive evidence of activity is still lacking. It is reasonable that cetuximab efficacy be restricted to tumors bearing wild-type KRAS and BRAF. Our study is aimed at determining KRAS and BRAF mutational status to evaluate the proportion of patients affected by biliary tract cancer who could benefit from EGFR-cascade targeted therapies. Methods: This is a retrospective analysis on 24 consecutive cases of cholangiocarcinoma undergone potentially curative resection in our institution. The mutational analyses have been conducted on the surgical specimen. After microdissection of the neoplastic area, DNA was extracted from enriched pathologic material with QIAmp DNA FFPE Tissue Kit (Qiagen S. p. A., Milan, Italy). Extracted DNA have been quantified after real-time PCR (Quantifiler Human DNA Quantification Kit, Applied Biosystems, Foster City, CA, USA) with ABI PRISM 7000 Sequence Detection System (Applied Biosystems). KRAS and BRAF mutations were detected in real-time PCR using specific commercially available kits (DxS Diagnostic, Manchester, UK) and confirmed with direct genomic sequencing of the same DNA specimen (Applied Biosystems 3730xl DNA Analyzer, Applied Biosystems). Results: Among patients included, 16 were extrahepatic cholangiocarcinomas and 8 intrahepatic; 14 pts showed lymph nodes involvement at surgery. 7 mutations of KRAS (all in exon 2, codon 12) and 2 of BRAF (1 in exon 11, 1 in exon 15) were identified, occurring respectively in 29% and 8% of patients. There were no double-mutated patients. 63% of study population (15 patients) was wild-type for both KRAS and BRAF. No relationship between mutational status and time to relapse has been found in this population (p 0.7). Conclusions: These preliminary data show that the majority of biliary tract cancer patients could benefit from anti-EGFR targeted therapies. Expansion of the number of patients and correlation with clinical data are ongoing. No significant financial relationships to disclose.
Clinical Features and Treatment Outcomes of Angioimmunoblastic T-Cell Lymphoma: An Analysis from a Nationwide Multicenter Registry, Thailand
Authors: Chittima Sirijerachai, Kanchana Chansung, Arnuparp Lekhakula, Jakrawadee Julamanee, Kitsada Wudhikarn, Udomsak Bunworasate, Lalita Norasetthada, Weerasak Nawarawong, Archrob Khuhapinant, Supachai Ekwattanakit, Tontanai Numbenjapon, Kannadit Prayongratana, Suporn Chuncharunee, Pimjai Niparuck, Tawatchai Suwanban, Nonglak Kanitsap, Somchai Wongkhantee, Peerapon Wong, Nisa Makruasi, Tanin Intragumtornchai
Journal: Blood (2015)
Hematopoietic Stem Cells Emerge in the Placental Vasculature in the Absence of Circulation.
Authors: Katrin E. Rhodes, Christos Gekas, Yanling Wang, Christopher T. Lux, Cameron S. Francis, Simon Conway, Stuart H. Orkin, Mervin C. Yoder, Hanna K.A. Mikkola
Journal: Blood (2007)
Adjunctive Azithromycin Prophylaxis for Cesarean Delivery
Authors: Alan T.N. Tita, Jeff M. Szychowski, Kim Boggess, George Saade, Sherri Longo, Erin Clark, Sean Esplin, Kirsten Cleary, Ron Wapner, Kellett Letson, Michelle Owens, Adi Abramovici, Namasivayam Ambalavanan, Gary Cutter, William Andrews
Journal: New England Journal of Medicine (2016)

The addition of azithromycin to standard regimens for antibiotic prophylaxis before cesarean delivery may further reduce the rate of postoperative infection. We evaluated the benefits and safety of azithromycin-based extended-spectrum prophylaxis in women undergoing nonelective cesarean section.In this trial conducted at 14 centers in the United States, we studied 2013 women who had a singleton pregnancy with a gestation of 24 weeks or more and who were undergoing cesarean delivery during labor or after membrane rupture. We randomly assigned 1019 to receive 500 mg of intravenous azithromycin and 994 to receive placebo. All the women were also scheduled to receive standard antibiotic prophylaxis. The primary outcome was a composite of endometritis, wound infection, or other infection occurring within 6 weeks.The primary outcome occurred in 62 women (6.1%) who received azithromycin and in 119 (12.0%) who received placebo (relative risk, 0.51; 95% confidence interval [CI], 0.38 to 0.68; P<0.001). There were significant differences between the azithromycin group and the placebo group in rates of endometritis (3.8% vs. 6.1%, P=0.02), wound infection (2.4% vs. 6.6%, P<0.001), and serious maternal adverse events (1.5% vs. 2.9%, P=0.03). There was no significant between-group difference in a secondary neonatal composite outcome that included neonatal death and serious neonatal complications (14.3% vs. 13.6%, P=0.63).Among women undergoing nonelective cesarean delivery who were all receiving standard antibiotic prophylaxis, extended-spectrum prophylaxis with adjunctive azithromycin was more effective than placebo in reducing the risk of postoperative infection. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development; C/SOAP ClinicalTrials.gov number, NCT01235546 .).