tbuckley/cabot-search huggingface dataset:
Abstract 5029: OT-101/Chemotherapy- A novel mechanism of action (MOA) in glioblastoma immunization therapy
Authors: Larn Hwang, David Nam, Fatih Uckun, Vuong Trieu
Journal: Cancer Research (2019)

Abstract Background: Escalating Intratumoral heterogeneity (IH) resulting in xenogenization which is countered by overexpression of TGF-β2. OT-101 is a TGF-β2-specific Phosphorothioate Antisense. Here we report the results of a randomized Phase 2b clinical trial (NCT00431561) comparing the safety and efficacy of OT-101 versus temozolomide (TMZ) in adult patients with WHO grade III/IV high-grade glioma. We took advantage of the known xenogenization activity of alkylating agent such TMZ to explore the impact of xenogenization on survival on treatment with OT-101. Methods: This is a phase 2b, multi-national, multi-center, open-label, active-controlled, randomized parallel group dose-finding study to evaluate the efficacy and safety of OT-101 in adult patients with recurrent high-grade glioma, administered intratumorally as continuous high-flow microperfusion over a 7-day period every other week. Results: A total of 134 patients, 89 patients in the OT-101 test group and 45 patients in the temozolomide (TMZ) group. OT-101 was superior to TMZ in doubling the number of pts in the good survival group, 64 of 97 pts (66%); whereas, only 14 of 45 pts (31%) treated with TMZ did (p=0.0001). mOSOT-101TMZSubseq. TMZSubseq. TMZ (or other alkylating agent)Prev. TMZNoYesNoYesNo4.2mos (N=14)26.2mos (N=30)5.6mos (N=8)13.2mos (N=9)Yes4.8mos (N=19)29.5mos (N=34)6.6mos (N=14)36.6 mos (N=14) There were two cases of neutropenia in the 90 pts treated with OT-101 versus 8, 10, and 8 pts with leukopenia, neutropenia, and thrombocytopenia, respectively, among 45 pts treated with TMZ (2% vs. 56%, p&amp;lt;0.0001). Conclusions: Improved survival was achieved by repeated exposure to TMZ/alkylating agent. This was further enhanced by OT-101 and consistent with the proposed MOA of OT-101/Chemo as reactivation of immunity during TGF-β suppression and subsequent xenogenization by TMZ. Citation Format: Larn Hwang, David Nam, Fatih Uckun, Vuong Trieu. OT-101/Chemotherapy- A novel mechanism of action (MOA) in glioblastoma immunization therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5029.
MAGNIFY: Phase IIIb interim analysis of induction R<sup>2</sup> followed by maintenance in relapsed/refractory indolent non-Hodgkin lymphoma.
Authors: David Jacob Andorsky, Morton Coleman, Abdulraheem Yacoub, Jason M. Melear, Suzanne R. Fanning, Kathryn Kolibaba, Frederick Lansigan, Chris Reynolds, Kenneth A. Foon, Jiahui Li, Mary Llorente, Mathias J. Rummel, Jeff Porter Sharman
Journal: Journal of Clinical Oncology (2019)

7513 Background: Standard treatment is lacking for patients with relapsed indolent NHL (iNHL). PI3K inhibitors reported a median PFS of &lt; 1 y in R/R iNHL. The immunomodulatory agent lenalidomide shows enhanced activity with rituximab (ie, R 2 ), which recently reported a 39.4-mo median PFS in R/R iNHL patients (AUGMENT; Leonard. ASH 2018:445). Methods: MAGNIFY is a multicenter, non-registrational phase IIIb trial in patients with R/R FL grade 1-3a and MZL designed to determine the optimal duration of lenalidomide. Lenalidomide 20 mg/d, d1-21/28 + rituximab 375 mg/m 2 /wk c1 and q8wk c3+ (R 2 ) are given for 12c followed by 1:1 randomization in patients with stable disease or better to continued R 2 vs rituximab maintenance. These analyses evaluate the primary endpoint of ORR by 1999 IWG criteria for induction R 2 in efficacy-evaluable patients receiving ≥ 1 treatment with baseline/post-baseline assessments. Results: At a median 16.7 mo follow-up, 370 patients (80% FL grade 1-3a; 20% MZL) were enrolled with a median age of 66 y, 83% stage III/IV disease, and a median of 2 prior therapies (95% prior rituximab-containing). Efficacy-evaluable patients showed a 73% ORR and 45% CR (Table). Median TTR was 2.7 mo, median DOR was 36.8 mo, and median PFS was 36.0 mo. 142 of 370 patients have been randomized and entered maintenance. The most common all-grade AEs were 48% fatigue, 40% neutropenia, 35% diarrhea, 30% nausea, and 29% constipation. Grade 3/4 AE neutropenia was 34%; all other grade 3/4 AEs were &lt; 6%. Conclusions: R 2 therapy is active with a tolerable safety profile in patients with R/R FL and MZL, and in patients refractory to rituximab. Clinical trial information: NCT01996865. [Table: see text]
Abstract 4027: XNA-Based OptiSeqTMlung and colorectal cancer mini panel, a high sensitivity method for cancer early detection
Authors: Michael Y. Sha, Wenjing Feng, Qing Sun, Ke Zhan, Michael J. Powell, Aiguo Zhang
Journal: Cancer Research (2019)

Abstract The identification of genetic variants with low allelic frequency using next-generation sequencing method is confounded by the complexity of human genome sequence and by bias that arise during library preparation, sequencing and analysis. Herein, we introduce a novel molecule, Xenonucleic Acid (XNA) for NGS application. XNA is able to selectively suppress primer directed amplification of DNA with wild type alleles and only amplify DNA target templates containing mutant alleles. Mutants with low allelic frequency will be easily detectable without deep sequencing after enrichment by adding XNA in multiplex PCR. The 17 actionable mutants related to lung or colorectal cancer diseases at different VAF% were investigated in this study. Upon XNA blocking of wild type alleles, enriched variant allelic frequency (VAF) can be increased by ~32 fold from 10 ng of gDNA samples containing mutants as low as 0.10% VAF. Analytical sensitivity of Limit of Detection (LOD) is about 0.10% VAF. These 17 actionable mutants were tested and verified by using tissue biopsy (FFPE) and liquid biopsy (cfDNA) of lung or colon cancer patient samples. Clinical sensitivity for FFPE sample is about 100% for lung cancer and colorectal cancer samples respectively, comparing to without XNA NGS about 85.7% for lung cancer and 70% for colon cancer. For cfDNA sample its clinical sensitivity is about 100% for lung and colon cancer, but without XNA mediated enrichment NGS is only about 70% for lung cancer and undetectable for early colon cancer. This method provides a simple, robust, accurate, faster turnaround, highly sensitive and low cost alternative compared conventional NGS employing deep sequencing. This technology will greatly enhance the adaptability of NGS as a clinically useful platform for every modern pathology laboratory. Citation Format: Michael Y. Sha, Wenjing Feng, Qing Sun, Ke Zhan, Michael J. Powell, Aiguo Zhang. XNA-Based OptiSeqTMlung and colorectal cancer mini panel, a high sensitivity method for cancer early detection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4027.
Abstract 676: Leveraging TCGA gene expression data to build predictive models for cancer drug response
Authors: Evan Clayton
Journal: Cancer Research (2019)

Abstract Personalized oncology promises to increase the success rate of cancer drug therapy by using molecular tumor profiles to determine the optimal therapeutic for an individual. 5-Fluorouracil and Gemcitabine are two Food and Drug Administration approved chemotherapeutics commonly prescribed to cancer patients. Here, we build machine learning models using gene expression data from patients’ primary tumors to predict their response, positive or negative, to these drugs. We compared several clustering and classification methods for predicting response. Of those tested, Clara was found to be the best clustering algorithm while random forest was the best classification method, with prediction accuracy up to 86%. We determined that models trained across several cancers outperform single cancer models. We also found that genes most informative for predicting drug response were enriched in well-known cancer signaling pathways, highlighting their potential significance in chemotherapy prognosis. Ultimately, such predictive models may aid oncologists with making critical treatment decisions. Citation Format: Evan Clayton. Leveraging TCGA gene expression data to build predictive models for cancer drug response [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 676.
Multiple Independent Recruitment of Sodefrin Precursor-Like Factors in Anuran Sexually Dimorphic Glands
Authors: Franky Bossuyt, Lisa M Schulte, Margo Maex, Sunita Janssenswillen, Polina Yu Novikova, S D Biju, Yves Van de Peer, Severine Matthijs, Kim Roelants, An Martel, Ines Van Bocxlaer
Journal: Molecular Biology and Evolution (2019)

Chemical signaling in animals often plays a central role in eliciting a variety of responses during reproductive interactions between males and females. One of the best-known vertebrate courtship pheromone systems is sodefrin precursor-like factors (SPFs), a family of two-domain three-finger proteins with a female-receptivity enhancing function, currently only known from salamanders. The oldest divergence between active components in a single salamander species dates back to the Late Paleozoic, indicating that these proteins potentially gained a pheromone function earlier in amphibian evolution. Here, we combined whole transcriptome sequencing, proteomics, histology, and molecular phylogenetics in a comparative approach to investigate SPF occurrence in male breeding glands across the evolutionary tree of anurans (frogs and toads). Our study shows that multiple families of both terrestrially and aquatically reproducing frogs have substantially increased expression levels of SPFs in male breeding glands. This suggests that multiple anuran lineages make use of SPFs to complement acoustic and visual sexual signaling during courtship. Comparative analyses show that anurans independently recruited these proteins each time the gland location on the male's body allowed efficient transmission of the secretion to the female's nares.
Human pancreatic islet three-dimensional chromatin architecture provides insights into the genetics of type 2 diabetes
Authors: Irene Miguel-Escalada, Silvia Bonàs-Guarch, Inês Cebola, Joan Ponsa-Cobas, Julen Mendieta-Esteban, Goutham Atla, Biola M. Javierre, Delphine M. Y. Rolando, Irene Farabella, Claire C. Morgan, Javier García-Hurtado, Anthony Beucher, Ignasi Morán, Lorenzo Pasquali, Mireia Ramos-Rodríguez, Emil V. R. Appel, Allan Linneberg, Anette P. Gjesing, Daniel R. Witte, Oluf Pedersen, Niels Grarup, Philippe Ravassard, David Torrents, Josep M. Mercader, Lorenzo Piemonti, Thierry Berney, Eelco J. P. de Koning, Julie Kerr-Conte, François Pattou, Iryna O. Fedko, Leif Groop, Inga Prokopenko, Torben Hansen, Marc A. Marti-Renom, Peter Fraser, Jorge Ferrer
Journal: Nature Genetics (2019)
Quality of life and psychological impact in the photodermatoses: a systematic review
Authors: K.J. Rutter, I. Ashraf, L. Cordingley, L.E. Rhodes
Journal: British Journal of Dermatology (2019)

Background The photodermatoses affect large proportions of the population but their impact on quality of life (QoL) and psychological health has not been reviewed. Several tools are available to evaluate QoL and psychological impacts. Objectives To systematically review current literature to identify tools used to assess QoL and psychological impacts in patients with photodermatoses, and to summarize the reported findings. Methods A systematic search of PubMed, OVID Medline, PsycInfo and CINAHL was performed for articles investigating QoL and/or psychological impact in patients with photodermatoses, published between 1960 and September 2018. Results Twenty studies were included: 19 incorporated QoL assessment while three evaluated psychological morbidity. Six QoL tools were found to be used: Dermatology Life Quality Index (DLQI), Children's DLQI, Family DLQI, Skindex (16- and 29-item versions), Erythropoietic Protoporphyria Quality of Life (EPP-QoL) and EuroQol. Between 31% and 39% of photosensitive patients reported a very large impact on QoL (DLQI > 10). Employment and education, social and leisure activities, and clothing choices were particularly affected. Only one tool was specifically designed for a photodermatosis (EPP-QoL). Four tools were used to evaluate psychological impact: the Hospital Anxiety and Depression Scale, Fear of Negative Evaluation, brief COPE and Illness Perception Questionnaire-Revised. Levels of anxiety and depression were approximately double British population data. Patients with facial involvement, female gender and younger age at onset showed more psychological morbidity. Conclusions Several tools have been used to assess QoL in the photodermatoses, and confirm substantial impact on QoL. Development of specific, validated QoL measures would address their unique impacts. Research delineating their psychological comorbidity is sparse and requires further exploration. What's already known about this topic? The photodermatoses negatively impact quality of life (QoL) and cause psychological distress, but no reviews of this area appear in the literature. What does this study add? Few studies have explored the psychological and social impacts of the photodermatoses. There are no fully validated QoL tools specific to the photodermatoses. Around one-third of adult and child patients with photosensitivity experience very or extremely large impact on QoL, with particular effect on clothing choices, employment and social and leisure activities. Studies suggest anxiety and depression levels in these patients are around double those in the U.K. general population. More attention is required on these ‘hidden’ conditions.
Poor prognosis of hypermutant colorectal cancer with KRAS mutations: A retrospective analysis of 1,052 Japanese colorectal cancer patients without treatment of immuno-checkpoint inhibitors
Authors: T. Nagasaka, H. Tanioka, A. Nyuya, Y. Katata, M. Okawaki, M. Yamamura, T. Kawai, K. Yasui, T. Toshima, Y. Mori, Y. Umeda, A. Tsuruta, T. Ueno, Y. Yamaguchi
Journal: Annals of Oncology (2019)
Response to: ‘Can biomarkers differentiate psoriatic arthritis from osteoarthritis?’ by Tian <i>et al</i>
Authors: Vinod Chandran, Richard J Cook, Dafna D Gladman
Journal: Annals of the Rheumatic Diseases (2019)

Response to: 'Can biomarkers differentiate psoriatic arthritis from osteoarthritis?' by Tian et alWe thank the authors for their interest in our paper that demonstrated that a panel of biomarkers may distinguish psoriatic arthritis (PsA) from osteoarthritis (OA). 1 We agree with the comments that diagnostic biomarkers are most useful when the two diseases are difficult to distinguish clinically especially at earlier stages.PsA and OA may be hard to distinguish when the distal (distal interphalangeal (DIP), proximal interphalangeal (PIP)) joints are predominantly involved.Moreover, when patients with psoriasis develop joint pain, it may be difficult to distinguish OA from PsA. 2 As a first step towards improving diagnostic ability using molecular biomarkers, in this particular study we aimed to provide proof of principle that a select panel of markers is able to distinguish between the two diseases using samples from patients with well-established disease.We did not adjust for disease severity since most patients with OA had advanced disease, and there is no common method to measure radiographic severity of OA and PsA.The association with disease severity was not investigated since that would be a different research/clinical question.As stated in Chandran et al, 3 future verification and validation studies will be conducted to examine the utility of this model in independent samples and to investigate whether other markers are identified for distinguishing OA from PsA in patients with psoriasis, particularly in the early disease stages.We could have tested other markers, some of which have been mentioned.We chose a limited set of markers of cartilage metabolism, metabolic syndrome and inflammation/immune response.The reasons behind our choice are discussed in the discussion section of the paper.
Abstract 1435: An ultra-sensitive and high-throughput technology (imPACT) for the identification and isolation of intrinsic and emergent neoepitope-specific T cells from the peripheral blood and TILs of cancer patients
Authors: Songming Peng, Boi Quach, Duo An, Salemiz Sandoval, Robert Bao, Zheng Pan, Michael Bethune, Olivier Dalmas, Michael Yi, Corey Meadows, Katherine Heeringa, Linlin Guo, Benjamin yuen, John Sorfleet, Kyle Jacoby, Robert Moot, William Lu, Diana Nguyen, Barbara Sennino, Andrew Conroy, Bhamini Purandare, Adam Litterman, Stefanie Mandl, Alex Franzusoff
Journal: Cancer Research (2019)

Abstract T cells capable of targeting neoepitopes (neoE) from tumor-specific mutations hold the potential to uniquely recognize and kill tumor cells. However, most cancer patients fail to mount a sufficient intrinsic T cell immune response to translate into clinical benefit. PACT Pharma has developed an ultra-sensitive and high-throughput technology (imPACT) for identifying and isolating neoE-specific T cells from peripheral blood. Whole exome sequencing of tumors and computational prediction identify patient-specific neoepitopes resulting from tumor-specific mutations. We then interrogate patient blood for neoE-specific T cells using human leukocyte antigen (HLA) protein-based reagents comprising a spectrum of human HLAs, thus enabling the evaluation of &amp;gt;99% of all individuals with cancer. We have identified and isolated neoE-specific T cells from the peripheral blood of &amp;gt;80% treatment-naive patients with bladder and colorectal cancers, melanoma and other solid tumors. Primary human T cells engineered with T cell receptor sequences (TCRs) cloned from the imPACT-isolated T cells gain the ability to kill cognate neoE-presenting tumor cells, thereby also confirming the specificity of the isolated TCR sequences to bind to the neoE target. This approach is also amenable to the longitudinal analysis of patients undergoing treatment for their cancers, to characterize the neoE-specific T cell populations likely to confer clinical benefit. In summary, the imPACT technology efficiently discovers potentially meaningful intrinsic neoE-specific TCRs from patients, enabling the development of personalized neoTCR-T cell therapies for the eradication of solid tumors. Citation Format: Songming Peng, Boi Quach, Duo An, Salemiz Sandoval, Robert Bao, Zheng Pan, Michael Bethune, Olivier Dalmas, Michael Yi, Corey Meadows, Katherine Heeringa, Linlin Guo, Benjamin yuen, John Sorfleet, Kyle Jacoby, Robert Moot, William Lu, Diana Nguyen, Barbara Sennino, Andrew Conroy, Bhamini Purandare, Adam Litterman, Stefanie Mandl, Alex Franzusoff. An ultra-sensitive and high-throughput technology (imPACT) for the identification and isolation of intrinsic and emergent neoepitope-specific T cells from the peripheral blood and TILs of cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1435.
Association Between Quantity of Opioids Prescribed After Surgery or Preoperative Opioid Use Education With Opioid Consumption
Authors: Kevin X. Farley, Albert T. Anastasio, Arun Kumar, Ajay Premkumar, Michael B. Gottschalk, John Xerogeanes
Journal: JAMA (2019)

This cohort study investigates the association between reducing the number of opioid tablets prescribed after anterior cruciate ligament (ACL) reconstruction and postoperative opioid consumption and between preoperative opioid use education about nonopioid pain strategies and duration and quantity of opioid use.
Abstract LB-214: Imputation of single cell cancer genotypes
Authors: Alex Zelikovsky, Igor Mandric, Pavel Skums, Ion Mandoiu, Bogdan Pasaniuc, Pramod Srivastava
Journal: Cancer Research (2019)

Abstract Recent advances in sequencing technologies and emerging single cell sequencing promise to profoundly impact cancer studies. One of the most important problems is reconstruction of history of cancer mutations. Existing methods model cells DNA as haplotypes and reconstruct perfect (or almost perfect) phylogeny of mutations from single cell DNA sequencing data. In this paper we propose to reconstruct genotypes (rather than haplotypes) which in absence of repeated and omitted mutations is equivalent to reconstruction of the mutation phylogeny. Single cell genotype reconstruction is proposed to perform in two steps - first the sequencing data are used for imputation of cell genotypes treated as individual human genomes and then the resulted genomes are fitted to perfect phylogeny by eliminating 4-gamete rule violations using integer linear programs. Our simulation results show advantage of single cell genotype imputation over existing methods. Note: This abstract was not presented at the meeting. Citation Format: Alex Zelikovsky, Igor Mandric, Pavel Skums, Ion Mandoiu, Bogdan Pasaniuc, Pramod Srivastava. Imputation of single cell cancer genotypes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-214.
Relationship between peripheral neuropathy and effectiveness in second-line chemotherapy for unresectable advanced gastric cancer: a prospective, observational, multicenter study protocol
Authors: H. Tanioka, T. Nagasaka, F. Uno, M. Inoue, H. Okita, Y. Katata, H. Kanzaki, H. Kuramochi, H. Satake, Y. Shindo, A. Doi, J. Nasu, H. Yamashita, Y. Yamaguchi
Journal: Annals of Oncology (2019)