tbuckley/cabot-search huggingface dataset:
Methylation reversal in high-grade B lymphoma cell lines and novel epigenetic changes conserved between immunocompetent and HIV-positive hosts
Authors: M. Bower, N. Syed, A. Papoudou-Bai, J. Stebbing, K. Naresh, E. Hatzimichael, S. Powles, T. Crook
Journal: Journal of Clinical Oncology (2009)

8585 Background: Methylation-dependent transcriptional silencing is an important mechanism of tumour suppressor gene inactivation in neoplasia, including lymphoma. Methods: Pharmacological “unmasking” of transcriptionally silenced genes in B lymphoma cell lines was achieved using 5' deazacytidine ± Trichostatin A and subsequent analysis of mRNA levels on micro-array. Candidate genes thus identified, were further analysed by qPCR, methylation-specific PCR (MSP) and bisulphite sequencing in B lymphoma cell lines and by MSP in clinical samples from sporadic (immunocompetent) (18 cases) and HIV-infected patients (14 cases). Samples in both patient groups were diffuse large B cell lymphoma (DLBCL) and Burkitt's lymphoma (BL). Additionally, we analysed 8 cases of marginal zone lymphoma (MZL) from the immunocompetent group. Results: We report the identification of 13 novel genes, not previously described in the literature, which are subject to methylation-dependent transcriptional silencing in high-grade lymphoma and whose expression can be reactivated by demethylating agents. The novel genes encode proteins involved in diverse functional classes and include pro-apoptotic members of the p53 pathway (Scotin), transcriptional regulators (Baz2B) and regulators of telomerase (Smrf2). The frequency of methylation in individual genes varied from approximately 10% to 75% in specific lymphoma subtypes, but was in general similar in high grade lymphomas in immunocompetent and HIV-infected hosts. Conclusions: Using pharmacological reversal of methylation, we have identified a number of genes, not previously implicated in human neoplasia, which are subject to transcriptional silencing in high-grade B lymphomas. The similar frequencies of methylation, observed in immunocompetent and HIV positive patients implies that the genes are fundamental in suppression of lymphomagenesis. Detection of methylated DNA of one or more of these genes may have utility as biomarkers of clinical outcome in each patient group. No significant financial relationships to disclose.
Impact of the Factor II G20210A Variant and the Factor V G1691A on Recurrent Venous Thromboembolism in Children: An International Multicentre Cohort Study.
Authors: Guy Young, Fauke Friedrichs, Neil Goldenberg, Gili Kenet, Marilyn Manco-Johnson, Christine During, Ulrike Nowak-Gottl
Journal: Blood (2007)
CONTRASTING US PATIENTS WITH A FILL VERSUS A PRESCRIPTION FOR ALIROCUMAB: EARLY EVIDENCE FROM ADMINISTRATIVE CLAIMS, EMR AND LAB DATA
Authors: Chakkarin Burudpakdee, Joseph Elassal, Velichka Valcheva, Katherine Gorcyca, Serban Iorga, Eli Roth
Journal: Journal of the American College of Cardiology (2017)
Phase I trial of ASG-5ME in metastatic castration-resistant prostate cancer (CRPC).
Authors: Michael J. Morris, Justine Yang Bruce, Leonard M. Reyno, Banmeet Anand, Alan Hartford, Kathy Jelaca-Maxwell, Jacqueline Lackey, Mario A. Eisenberger
Journal: Journal of Clinical Oncology (2012)

4568 Background: SLC44A4 is a 710 amino acid protein that is expressed on prostate, pancreas and other cancers. SLC44A4 is found in 95% of primary prostate tumors (75% express moderate to high levels). ASG-5ME is an antibody drug conjugate (ADC) comprised of a fully human antibody targeting SLC44A4, conjugated to the microtubule-disrupting agent monomethyl auristatin E. ASG-5ME has dose-dependent cytotoxic effects in vitro and significant anti-tumor activity in xenograft models. We report results of a phase I study to establish the maximum tolerated dose (MTD) of ASG-5ME for CRPC, conducted by the Prostate Cancer Clinical Trials Consortium. Methods: Patients (pts) had progressive metastatic CRPC. Prior chemotherapy was allowed. Treatment cohorts were 0.3, 0.6, 1.2, 1.8, 2.4, and 3.0 mg/kg. ASG-5ME was given IV q3 weeks. Safety, pharmacokinetic properties, anti-tumor effects, circulating tumor cell (CTC) enumeration, and CTC molecular profiles were assessed. Pts were treated until disease progression or unacceptable toxicity. Dose limiting toxicity (DLT) was defined by cycle 1 toxicity. Results: 20 pts have been treated (3, 3, 3, 3, 6, and 2 pts per respective cohort). Mean age was 69 (range 56-87), median Gleason score 8 (6-10), mean baseline PSA 225 (5-1987). Pts received an average of 4 doses (1-12). 2 DLTs occurred in Cycle 1 in the 3 mg/kg cohort: DLT 1: Grade (Gr) 3 troponin elevation and DLT 2: Gr3 maculopapular rash, hypoxia, constipation, and Gr4 neutropenia. Common Gr 1 and 2 adverse events included fatigue, anorexia, peripheral neuropathy, dyspnea and nausea. Gr3 events included: fatigue (2 pts),peripheral neuropathy (1), dyspnea (1) and nausea (1). Serum concentrations of ASG-5ME decreased multi-exponentially and the exposure was dose-proportional. The half-life of intact drug was calculated as 7.01 days (range-3.93-15.9, n=17) after the first dose and 11.2 days ( range-7.75-19.1 days, n=10) after the last dose. PSA declines of &gt;50% were seen in 3/8 pts treated in the last two cohorts and one unconfirmed &gt;50% decrease in retroperitoneal nodes. Conclusions: DLT events observed at 3 mg/kg exceeded the MTD; the MTD is 2.4 mg/kg of doses tested in pts with metastatic CRPC. The drug appears to have anti-cancer activity at 2.4 and 3 mg/kg.
SERUM ALBUMIN AS AN INCREMENTAL PREDICTOR OF MORTALITY IN OLDER ADULTS UNDERGOING TRANSCATHETER AORTIC VALVE REPLACEMENT: RESULTS FROM THE MULTICENTER FRAILTY-AVR STUDY
Authors: Michael Goldfarb, Sandra Lauck, John Webb, Dae Hyun Kim, Jeffrey Popma, Nicolo Piazza, Giuseppe Martucci, Marino Labinaz, Andre Lamy, Mark Peterson, Nicolas Noiseux, Andrew Rassi, Brian Lindman, Philippe Genereux, Rakesh Arora, José Morais, Anita Asgar, Louis Perrault, Jonathan Afilalo
Journal: Journal of the American College of Cardiology (2017)
DO CARDIOVASCULAR HEALTH SCREENING PROGRAMS AND FOCUSED COUNSELING HAVE IMPACT ON PATIENT HABITS AND LIFESTYLE CHANGE? EARLY RESULTS OF THE HEART SMART SCREENING PROGRAM
Authors: Paul Nona, Aayush Mittal, Karthik Pattiala, Kristen Brooks, Maria Tyler Moore, Karthikeyan Ananthasubramaniam
Journal: Journal of the American College of Cardiology (2017)
EXERTIONAL HYPOXEMIA IN LEVO-TRANSPOSITION OF THE GREAT ARTERIES (L-TGA) AND PULMONARY STENOSIS DUE TO PULMONARY ARTERY CONDUIT STENOSIS AND ATRIAL SEPTAL DEFECT
Authors: Joanna M. Joly, Arka Chatterjee, Marc Cribbs, Mark Law
Journal: Journal of the American College of Cardiology (2017)
The Imprinted Dlk1-Gtl2 Locus Epigenetically Regulates Primitive Hematopoietic Stem Cell Mitochondrial Function and Energy Metabolism Via Repression of PI3K/Akt/mTOR Pathway
Authors: Pengxu Qian, Xi He, Ariel Paulson, Jeffrey S. Haug, Linheng Li
Journal: Blood (2014)
Testosterone Replacement Therapy and Risk of Favorable and Aggressive Prostate Cancer
Authors: Stacy Loeb, Yasin Folkvaljon, Jan-Erik Damber, Joseph Alukal, Mats Lambe, Pär Stattin
Journal: Journal of Clinical Oncology (2017)

Purpose The association between exposure to testosterone replacement therapy (TRT) and prostate cancer risk is controversial. The objective was to examine this association through nationwide, population-based registry data. Methods We performed a nested case-control study in the National Prostate Cancer Register of Sweden, which includes all 38,570 prostate cancer cases diagnosed from 2009 to 2012, and 192,838 age-matched men free of prostate cancer. Multivariable conditional logistic regression was used to examine associations between TRT and risk of prostate cancer (overall, favorable, and aggressive). Results Two hundred eighty-four patients with prostate cancer (1%) and 1,378 control cases (1%) filled prescriptions for TRT. In multivariable analysis, no association was found between TRT and overall prostate cancer risk (odds ratio [OR], 1.03; 95% CI, 0.90 to 1.17). However, patients who received TRT had more favorable-risk prostate cancer (OR, 1.35; 95% CI, 1.16 to 1.56) and a lower risk of aggressive prostate cancer (OR, 0.50; 95% CI, 0.37 to 0.67). The increase in favorable-risk prostate cancer was already observed within the first year of TRT (OR, 1.61; 95% CI, 1.10 to 2.34), whereas the lower risk of aggressive disease was observed after &gt; 1 year of TRT (OR, 0.44; 95% CI, 0.32 to 0.61). After adjusting for previous biopsy findings as an indicator of diagnostic activity, TRT remained significantly associated with more favorable-risk prostate cancer and lower risk of aggressive prostate cancer. Conclusion The early increase in favorable-risk prostate cancer among patients who received TRT suggests a detection bias, whereas the decrease in risk of aggressive prostate cancer is a novel finding that warrants further investigation.
Oxaliplatin (L-OHP) in combination with 5-fluorouracil (5-FU)/<b><i>l</i></b>-leucovorin (<b><i>l</i></b>-LV) on modified Roswell Park regimen as first-line treatment of advanced colorectal cancer (ACRC): A phase I/II study
Authors: Y. Miyata, K. Shirao, A. Ohtsu, N. Boku, Y. Tanigawara
Journal: Journal of Clinical Oncology (2004)

3705 Background: L-OHP has been established as a key drug for ACRC, and FOLFOX 4 is commonly used in Europe and the US. We conducted this trial to determine the recommended dose (RD) and evaluate safety and efficacy of L-OHP + weekly bolus 5-FU/l-LV as first-line treatment of ACRC. Methods: Inclusion criteria were unresectable ACRC, no prior chemotherapy, PS (ECOG) 0–2, age 20 - 75 years, measurable lesions, and adequate organ functions. L-OHP was administered over 2 hours (hrs) IV on days 1, and 15 with l-LV over 2 hrs IV and 5-FU IV bolus on days 1, 8, and 15 every 28 days. Doses of L-OHP and l-LV were fixed at 85 mg/m2 and 250 mg/m2 respectively, and that of 5-FU was escalated from 400 mg/m2 (level 1) to 500 mg/m2 (level 2). RD was determined in a formal phase I dose escalation manner, and safety and efficacy were evaluated according to NCI-CTC v2.0 and RECIST guidelines. Results: No dose-limiting toxicity (DLT) was observed at level 1 (n = 3), but at level 2 (n = 4), 3 patients (pts) experienced DLTs in the first cycles; grade (G) 3 thrombocytopenia, G4 neutropenia, and G2 neutropenia required treatment delay over 7 days. Level 1 was therefore determined as the RD, and 11 pts more were accrued at this dose. A total of 18 pts (14 at RD) were enrolled. Male /female = 11/7, PS 0/1/2 = 15/3/0, median age 63 years (range 37 - 73), colon/rectum = 14/4. Median number of cycles treated was 5.5. Peripheral neuropathy was observed in all 18 pts, but with no functional impairment. G3 toxicities at RD were as follows: neutropenia in 2 pts, hemoglobin decreased, lymphopenia in 1 pt each. Overall response rate was 61% (CR/PR/SD/PD=0/11/7/0). Median progression-free survival was 170 days. Conclusions: L-OHP + weekly bolus 5-FU/l-LV regimen was well tolerated. Efficacy and safety appear to be comparable to those of FOLFOX 4. (Supported by Yakult Honsha Co., Ltd.) No significant financial relationships to disclose.
Clinical improvement with a novel CD20 mAb, ofatumumab, in fludarabine-refractory chronic lymphocytic leukemia (CLL) also refractory to alemtuzumab or with bulky lymphadenopathy
Authors: T. J. Kipps, A. Österborg, J. Mayer, S. Stilgenbauer, A. Hellmann, C. D. Williams, R. Furman, G. Chan, C. Russell, W. G. Wierda
Journal: Journal of Clinical Oncology (2009)

7043 Background: Patients (pts) with CLL refractory tofludarabine and alemtuzumab (double-refractory, DR) or refractory to fludarabine with bulky (&gt;5 cm) lymphadenopathy (bulky fludarabine-refractory, BFR) have a poor prognosis. Ofatumumab is a human mAb specific for a distinctive small-loop epitope of CD20 that appears more potent than rituximab in eliciting complement-dependent lysis of B cells in vitro. We report, for the first time, results from the planned interim analysis of the clinical benefit observed in pts with DR or BFR CLL treated with ofatumumab in an international pivotal clinical study. Methods: Pts with DR or BFR CLL received 8 weekly then 4 monthly ofatumumab infusions (Dose 1, 300 mg; Doses 2–12, 2,000 mg). Primary endpoint was overall response rate (ORR; 1996 NCI-WG criteria), as assessed by an Independent Review Committee, over 24 wks. Results: Of 138 treated pts (DR: N = 59; BFR: N = 79; median age 64 and 62 yrs, respectively), 63% had Rai stage III/IV disease at screening. Pts had a median of 5 prior therapies. ORR (99% CI) was 58% (40, 74%) in the DR and 47% (32, 62%) in the BFR groups, and median overall survival (95% CI) was 13.7 mo (9.4, NR) and 15.4 mo (10.2, 20.2), respectively. Resolution of disease symptoms (maintained for ≥2 mo) were observed in a large proportion of pts (Table), including in pts considered nonresponders by NCI-WG criteria. Improvements in hematologic values were also observed in some pts with abnormal baseline values, particularly for platelet counts. Pts with thrombocytopenia at baseline (n = 73) experienced sustained increases in median platelet counts from 65 × 10 9 /L to over 100 × 10 9 /L by Wk 8; a similar pattern of rapid improvement was observed in Hgb values. Conclusions: Ofatumumab as single-agent achieves high ORR, and improves disease symptoms and hematologic parameters in heavily pretreated pts with DR and BFR disease who lack standard treatment options. [Table: see text] [Table: see text]
IHP Interpretation Criteria of Interim-PET Scan Confirms Prognostic Impact In Early Stage Hodgkin Lymphoma Patients without Bulky Disease
Authors: Luigi Rigacci, Pier Luigi Zinzani, Benedetta Puccini, Alessandro Broccoli, Andrea Gallamini, Francesco Merli, Vittorio Stefoni, Caterina Stelitano, Monica Balzarotti, Patrizia Pregno, Ercole Brusamolino, Flavia Salvi, Pietro Maria Stefani, Rosaria Sancetta, Rita Emili, Silvia Tavera, Ida Capodanno, Umberto Vitolo, Cinzia Pellegrini, Anna Marina Liberati, Alberto Bosi
Journal: Blood (2010)
INTRAVASCULAR ULTRASOUND ASSESSMENT OF THE EFFECTS OF ROTATIONAL ATHERECTOMY IN CALCIFIED CORONARY ARTERY LESIONS
Authors: Myong Hwa Yamamoto, Sung Sik Kim, Akiko Maehara, Kohei Koyama, Colin Berry, Keith Oldroyd, Gary Mintz, Margaret McEntegart
Journal: Journal of the American College of Cardiology (2017)
Measurement of gene expression biomarkers by qNPA from archived NSCLC FFPE: Prognosis of 5-year survival
Authors: M. M. Joshi, B. Seligmann, C. Sabalos, D. H. Harpole
Journal: Journal of Clinical Oncology (2009)

11098 Background: There are vast archives of formalin fixed paraffin-embedded (FFPE) tissue samples that are clinically annotated offering great research potential. However, the technology currently available to assess gene expression is limited to fresh, frozen, tissue. Recently, a method for measuring gene expression from FFPE using the quantitative Nuclease Protection Assay (qNPA) has been published in a model of diffuse large B-cell lymphoma. It was demonstrated that identical results were obtained from small amounts of FFPE as from matched frozen tissue, or from freshly fixed versus 18 year archived FFPE. Methods: This study used the qNPA assay to measure gene expression in archived FFPE primary tumor samples of patients with stage 1 NSCLC for whom the survival outcomes are known (n=86). HTG lysis buffer is added to the sample; nuclease protection probes that are complementary to the mRNA of interest are then added to the solution. The probes hybridize to all RNA, soluble and cross-linked. After hybridization, S1 nuclease was added and destroys all nonspecific, single strand nucleic acid, producing a stoichiometric amount of target-mRNA to probe duplexes. Base hydrolysis releases the probe from these duplexes. Probes were transferred to a programmed ArrayPlate, detection linker added, and both probes and detection linkers were captured onto the array. The ArrayPlate was washed, HRP-labeled detection probe added, incubated, washed, and chemiluminescent substrate was added. Finally, the ArrayPlate was imaged, to measure the expression of each gene in all the wells. Results: Mantel-Cox analysis indicates that the detection of increased expression of G-CSF (p = 0.07; H.R. =1.904; 95% CI=0.9003–4.028) and Leptin (p=0.09; H.R. =1.910; 95% CI=0.9299–3.924) individually suggest an improved survival. Age, gender and T size were found to not be significant in this data set. Conclusions: These results suggest an improved survival advantage in patients with an elevated native GCSF level in stage 1 NSCLC that is consistent with the survival benefits associated with the prophylactic treatment of GCSF for chemosensitivity in stage III or IV NSCLC patients. These results are currently being assessed using a larger cohort. [Table: see text]
Assessment of penetration potential of pH responsive double walled biodegradable nanogels coated with eucalyptus oil for the controlled delivery of 5-fluorouracil: In vitro and ex vivo studies
Authors: Prashant Sahu, Sushil K. Kashaw, Sanyog Jain, Samaresh Sau, Arun K. Iyer
Journal: Journal of Controlled Release (2017)
Impact of the Use of Thalidomide, Lenalidomide, or Bortezomib, Compared to“standard Chemotherapy”, as “salvage” Before Reduced Intensity Conditioning Allogeneic Stem Cell Transplantation (RIC-AT), for Relapsed Multiple Myeloma
Authors: Anna Schmitt, Reza Tabrizi, Stephane Vigouroux, Mathieu Sauvezie, Carine Foucaud, Krimo Bouabdallah, marie-Sarah Dilhuydy, Arnaud Pigneux, Thibaut Leguay, didier-Innocent Adiko, Jean-Michel Boiron, Gerald Marit, Noel-Jean Milpied
Journal: Blood (2008)
Long Term Follow-up of IL-1 Receptor Antagonist and Dexamethasone Phase II Clinical Trial in Patients with Smoldering/Indolent Myeloma Shows Improved Survival in Responsive Patients: Implications for Targeting Interleukin-1 Induced IL-6 Production and the Myeloma Proliferative Component
Authors: John A Lust, Martha Q Lacy, Steven R Zeldenrust, Angela Dispenzieri, Morie A Gertz, Philip R. Greipp, Thomas E. Witzig, Shaji Kumar, Laurie L. Moon-Tasson, S. Vincent Rajkumar, Kathleen A. Donovan
Journal: Blood (2011)
PERIPHERAL ENDOTHELIAL FUNCTION ASSESSMENT OF PATIENTS ON TICAGRELOR VERSUS CLOPIDOGREL WHO HAVE UNDERGONE PERCUTANEOUS CORONARY INTERVENTION: A RANDOMIZED, CROSSOVER STUDY
Authors: Ronstan Lobo, Kirsten Mannix, Catriona Ahern, Ailish Hannigan, Syed Abbas, Terence Hennessy, Thomas B. Meany, Thomas J. Kiernan
Journal: Journal of the American College of Cardiology (2017)
EFFECT OF INHALED NEBULIZED NITRITE ON PULMONARY ARTERIAL PRESSURE IN HBE/BETA-THALASSEMIA PATIENTS WITH PULMONARY ARTERIAL HYPERTENSION
Authors: Teewin Rakyhao, Nathawut Sibmooh, Suporn Chuncharunee, Piyamitr Sritara, Teerapat Yingchoncharoen
Journal: Journal of the American College of Cardiology (2017)
Phase I open-label, multiple ascending dose trial of MSB0010718C, an anti-PD-L1 monoclonal antibody, in advanced solid malignancies.
Authors: Christopher Ryan Heery, Geraldine Helen O'Sullivan Coyne, Ravi Amrit Madan, Jeffrey Schlom, Anja von Heydebreck, Jean-Marie Cuillerot, Helen Sabzevari, James L. Gulley
Journal: Journal of Clinical Oncology (2014)

3064 Background: MSB0010718C is a fully human IgG1 monoclonal antibody targeting the coregulatory protein Programmed Death (PD)-Ligand 1 (PD-L1). PD-1/PD-L1 interactions induce T-cell anergy, protecting tumor cells from elimination by the immune system. MSB0010718C is expected to have antitumor activity by restoring immune system activity and through ADCC. Objectives: Assess the safety of MSB0010718C and determine its maximum tolerated dose, and analyze its pharmacokinetic (PK) profile and target receptor occupancy (RO). Methods: Twenty-seven patients (pts) with refractory malignancies have been enrolled and treated to date. Dose escalation (3+3 design) has been performed for 4 dose levels (1, 3, 10, and 20 mg/kg, q2w). After dose-level safety was determined, accrual of additional pts was allowed in order to generate additional safety, PK, and RO data. Results: Four, 11, 6, and 6 pts have been accrued to dose levels 1–4, respectively. Median pt age is 64 years (range 34–77), ECOG 0–1, with a median of 2 prior lines of therapy for metastatic disease (range 0–5). Eleven pts received prior immunotherapy (range 1–2 lines). Twenty-three pts have been followed for at least 4 weeks by Jan 7, 2014. To date, 12 pts (52.2%) have come off study: 9 (39.1%) for progression, 2 (8.7%) for adverse events (AEs), and 1 (4.3%) for death. Grade ≥3 AEs attributable to drug comprised laboratory abnormalities in 3 pts (2 pts with grade 3 AEs; 1 pt with a grade 4 AE). One DLT was observed in 1 pt at dose level 4: an immune-related AE with creatine kinase increase, myositis and myocarditis. Data from 25 pts were evaluable for PK and RO analysis. Median time to maximum concentration for all doses was approximately 1.5 to 2 h after infusion, with a linear PK. Half-life was 63.4, 80.7, 93.9, and 115.1 h for dose levels 1, 2, 3, and 4, respectively, as measured by ELISA. Target RO data were available for 13 pts, as measured by PD-L1 binding on peripheral leukocytes via flow cytometry. Mean RO prior to second infusion was 75.7, 93.8, and 93.2% for dose levels 1, 2, and 3, respectively. Conclusions: MSB0010718C can be safely administered in doses up to 20 mg/kg IV every 2 weeks. Clinical trial information: NCT01772004.
Practical application of whole genome and transcriptome tumour analysis to guide chemotherapy decision-making for patients with advanced cancers.
Authors: Janessa J. Laskin, Howard John Lim, Karen A. Gelmon, Cheryl Ho, Daniel John Renouf, Stephen Yip, David Huntsman, Anna Tinker, Erin Pleasance, Yvonne Li, Yaoqing Shen, Katayoon Kasaian, Richard Corbett, Karen Mungall, Andrew Mungall, Yongjun Zhao, Jacquie Schein, Robyn Roscoe, Steven Jones, Marco Marra
Journal: Journal of Clinical Oncology (2013)

e22020 Background: We propose that applying personal genomic information prospectively, in a clinically realistic timeframe can aid chemotherapy decision-making and result in more effective cancer treatment. We are investigating this approach in a variety of cancers to examine timeliness, deliverability, and rate of actionable targets identified. Methods: Eligible subjects with incurable cancer and limited chemo options have a tumour biopsy and “normal” blood taken for analysis. Archival specimens are concurrently analyzed to look for changes with time and treatment. Samples are subject to both an Ampliseq amplicon panel and in-depth whole genome DNA and RNA sequencing (WGS). Bioinformatics approaches identity genes with somatic and copy number variations, and expression changes. Variants are integrated into a pathway analysis to identify tumour specific processes that may drive the tumour, these are then matched to drug databases, with manual literature reviews, to indentify drugs that may be useful or even contra-indicated. Results: Between July 2012 -Jan 2013, 9 subjects (of 30 planned) are enrolled: 2 cases each of: colorectal and breast and 1 each of: squamous skin, squamous ethmoid sinus, nasopharyngeal, lung, and CLL-peripheral mantle cell cancer. 5 have completed analyses. Cancer panel results correlated well with WGS; although the panel is more rapid, it provides less comprehensive information and has not been as informative for identifying candidate druggable drivers. Extensive pathway mapping uncovered potential drug targets in each case that would not have necessarily been considered without this analyses. To date, 4 subjects have started chemo based on the analyses and 1 patient has had his diagnosis radically changed. There are significant genomic differences between archival and fresh tumour samples. Conclusions: This approach is feasible and yields actionable targets that can inform real-time chemotherapy decision-making. Archival samples do not appear to adequately represent post-treatment cancers. The impact of WGS vs. panel sequencing will require more subjects but it appears a panel may be insufficient for detailed treatment guidance.
Antitumor Activity of An RNA-Based Agonist of TLR7 and 8 In Preclinical Models of Hematological Malignancies
Authors: Daqing Wang, Melissa Precopio, Michael Reardon, Tao Lan, Jimmy X Tang, Ekambar R Kandimalla, Nicola La Monica, Sudhir Agrawal
Journal: Blood (2010)