tbuckley/cabot-search huggingface dataset:
Abstract 4029: Analysis of DLL3 and ASCL1 in surgically resected small cell lung cancer (HOT1702)
Authors: Megumi Furuta, Jun Sakakibara-Konishi, Hajime Kikuchi, Hiroshi Yokouchi, Hiroshi Nishihara, Hiroyuki Minemura, Masao Harada, Shigeo Yamazaki, Kenji Akie, Yuka Fujita, Kei Takamura, Tetsuya Kojima, Toshiyuki Harada, Yoshinori Minami, Naomi Watanabe, Satoshi Oizumi, Hiroyuki Suzuki, Masaharu Nishimura, Hirotoshi Dosaka-Akita, Hiroshi Isobe
Journal: Cancer Research (2019)

Abstract Background:Delta-like protein 3 (DLL3) is a Notch ligand that has an important role in the tumorigenesis of small cell lung cancer (SCLC). Recently, rovalpituzumab tesirine (Rova-T), a DLL3-targeted antibody-drug conjugate, has been developed for treating SCLC and has shown improved clinical response in patients with high DLL3 expression. DLL3 is a transcriptional target of the achaete-scute homolog-1(ASCL1) transcription factor, which is involved in pulmonary neuroendocrine cell development. However, the relationship between DLL3 and/or ASCL1 expression and the clinical features of SCLC remains unknown, especially for early-stage resected SCLC. This study aimed to investigate the expression of DLL3 and ASCL1 in resected SCLC samples using immunohistochemical analysis. Materials and Methods:We collected 95 formalin-fixed and paraffin-embedded SCLC samples, which were surgically resected at 11 institutions participating in either the Hokkaido Lung Cancer Clinical Study Group Trial (HOT) or the Fukushima Investigative Group for Healing Thoracic Malignancy (FIGHT) between 2003 and 2013. Immunohistochemistrystaining was performed to investigate the correlation between the expression of either DLL3 or ASCL1 and clinicopathological features of study patients. Results:Seventy-seven (83%) of 93 immunohistochemically evaluable samples were positive for DLL3 (expression in ≥ 1% of tumor cells), and DLL3-high expression (≥ 75%) was observed in 44 samples (47%). Sixty-one (64%) of 95 samples were positive for ASCL1 (expression in ≥ 5% of tumor cells). A positive correlation was observed between DLL3 and ASCL1 expression. DLL3 and ASCL1 expression were not associated with survival in SCLC patients. DLL3 and ASCL1 were more prevalent in patients with advanced clinical disease and pure SCLC, respectively. Conclusion:DLL3 and ASCL1 were highly expressed in surgically resected SCLC patients. Citation Format: Megumi Furuta, Jun Sakakibara-Konishi, Hajime Kikuchi, Hiroshi Yokouchi, Hiroshi Nishihara, Hiroyuki Minemura, Masao Harada, Shigeo Yamazaki, Kenji Akie, Yuka Fujita, Kei Takamura, Tetsuya Kojima, Toshiyuki Harada, Yoshinori Minami, Naomi Watanabe, Satoshi Oizumi, Hiroyuki Suzuki, Masaharu Nishimura, Hirotoshi Dosaka-Akita, Hiroshi Isobe. Analysis of DLL3 and ASCL1 in surgically resected small cell lung cancer (HOT1702) [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 4029.
Promoting Breast Cancer Surveillance: The EMPOWER Study, a Randomized Clinical Trial in the Childhood Cancer Survivor Study
Authors: Kevin C. Oeffinger, Jennifer S. Ford, Chaya S. Moskowitz, Joanne F. Chou, Tara O. Henderson, Melissa M. Hudson, Lisa Diller, Aaron McDonald, James Ford, Nidha Z. Mubdi, Dayton Rinehart, Christopher Vukadinovich, Todd M. Gibson, Nassim Anderson, Elena B. Elkin, Kathleen Garrett, Margaret Rebull, Wendy Leisenring, Leslie L. Robison, Gregory T. Armstrong
Journal: Journal of Clinical Oncology (2019)

The aim of the current study was to increase the uptake of screening mammography among high-risk women who were treated for a childhood cancer with chest radiotherapy.Two hundred four female survivors in the Childhood Cancer Survivor Study who were treated with chest radiotherapy with 20 Gy or greater, age 25 to 50 years, and without breast imaging in the past 24 months were randomly assigned 2:1 to receive a mailed informational packet followed by a tailored telephone-delivered brief motivational interview (intervention) versus an attention control. Primary outcome was the difference in the proportion of participants who completed a screening mammogram by 12 months as evaluated in an intent-to-treat analysis. Stratum-adjusted relative risk (RR) and 95% CI were estimated using the Cochran-Mantel-Haenszel method. Secondary outcomes included the completion of screening breast magnetic resonance imaging (MRI) and barriers to screening and moderating factors.Women in the intervention group were significantly more likely than those in the control group to report a mammogram (45 [33.1%] of 136 v 12 [17.6%] of 68; RR, 1.9; 95% CI, 1.1 to 3.3). The intervention was more successful among women age 25 to 39 years (RR, 2.2; 95% CI, 1.1 to 4.7) than among those age 40 to 50 years (RR, 1.4; 95% CI, 0.6 to 3.2). The proportion of women who reported a breast MRI at 12 months was similar between the two groups: 16.2% (intervention) compared with 13.2% (control; RR, 1.2; 95% CI, 0.6 to 2.5). Primary barriers to completing a screening mammogram and/or breast MRI included lack of physician recommendation, deferred action by survivor, cost, and absence of symptoms.Use of mailed materials followed by telephone-delivered counseling increased mammography screening rates in survivors at high risk for breast cancer; however, this approach did not increase the rate of breast MRI. Cost of imaging and physician recommendation were important barriers that should be addressed in future studies.
Role of killer cell immunoglobulin-like receptor (KIR)-ligand interactions to prevent relapse in patients (pts) receiving matched unrelated stem cell transplant (SCT) for acute myeloid leukemia (AML).
Authors: Hind Rafei, Marcelo Fernández-Viña, Yudith Carmazzi, Brandt Moore, Dana Willis, Rafet Basar, Pinaki Prosad Banerjee, May Daher, Chitra Hosing, Partow Kebriaei, Issa F. Khouri, Rohtesh Mehta, Yago Nieto, Muzaffar H. Qazilbash, Elizabeth J. Shpall, Richard E. Champlin, David Marin, Katayoun Rezvani, Kai Cao
Journal: Journal of Clinical Oncology (2019)

7049 Background: NK cells play a pivotal role in cancer immune vigilance. NK cell function is regulated by a balance between activating and inhibitory signals derived from various receptor-ligand interactions. Methods: 390 AML pts received 10/10 unrelated donor SCT. KIR genotype was performed by PCR with sequence specific primers. Hazard ratio (HR) for 2-year relapse was calculated using Fine-Gray regression and adjusted for disease risk index, remission status, pre-SCT MRD, conditioning regimen and presence of HLA-DP mismatch. KIR-ligand (K-L) match was defined as the presence a given KIR in the donor and the presence of its reported ligand in the patient (ex. 2DL1 and HLA-C2). KIRs that have no known ligands were not included in this analysis. The Table shows pt characteristics and K-L matches. Results: There was no correlation between the number of inhibitory or activating KIRs or KIR haplotype (A or B) and the probability of relapse after SCT. However, donor KIRs had a dramatic effect on relapse when they were considered together with the presence of the corresponding ligand in the pt. The 210 pts who had ≥3 inhibitory K-L matches had a significantly higher probability of relapse (HR=1.748, CI=1.147-2.667, p=0.009) than the remaining 180 pts. Similarly, the 96 pts who had at least one known activating K-L match had a lower probability of relapse (HR=0.581, CI=0.345-0.978, p=0.04). When we considered inhibitory and activating K-L matches together, we found that the 168 pts who had ≥3 inhibitory and no activating K-L matches had a significantly higher probability of relapse (HR 2.001, CI=1.376-2.908, p&lt;0.001) than the 222 remaining pts. Conclusions: Donor-pt KIR-ligand matching should be taken into account when choosing unrelated donors for AML pts. [Table: see text]
Abstract 90: The “reproducibility crisis” of animal studies in oncology - How did we get here, and how can we resolve it
Authors: Hannes Hentze, Eric Ibsen
Journal: Cancer Research (2019)

Abstract Historically, a large majority of clinical phase III trials fail to gain regulatory approval due primarily to a lack of demonstrated efficacy, demonstrating the challenge of conducting clinically relevant efficacy studies in laboratory animals. In 2012, Amgen researchers published their finding that an astoundingly-high proportion (90%) of more than 50 republished in vivo studies in oncology was not reproducible. This sparked an intense debate about data validity in preclinical sciences, and several reviews have been published in the last two years analysing this issue. A number of best-practice initiatives and resources have since been created along with the development of animal study workflow software applications and databases to address the causes of this significant, global problem in cancer research. Major sources of irreproducibility in animal research such as bias, suboptimal disease models, lack of controls, and most importantly bad documentation practices will be discussed. Several initiatives have resulted in practically-applicable concepts and publicly-available resources to address this issue, such as ARRIVE guidelines, PHISPS protocols and the N3R Design Assistant, will be described. Electronic spreadsheets have been the most prevalently-used tool to plan and conduct preclinical efficacy studies in oncology. The advent of animal study workflow software and database technology, designed specifically for in vivo oncology research, has seen increasingly widespread adoption in recent years in both academia and industry. By employing standardized and more detailed approaches to the processes documenting highly detailed study design, data collection, method and procedure descriptions and adherence, real-time monitoring of animal welfare parameters, standardized graphing, data analyses and report generation, measurement and task scheduling, as well as data preservation approaches, will be explored. Using some real-life examples, the advantages and disadvantages of preclinical study automation and the use of electronic spreadsheets will be discussed in the context of helping to resolve the animal study “Reproducibility Crisis”. Citation Format: Hannes Hentze, Eric Ibsen. The “reproducibility crisis” of animal studies in oncology - How did we get here, and how can we resolve it [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 90.
Apatinib as non-first-line treatment in patients with advanced cholangiocarcinoma
Authors: J. Lin, X. Yang, J. Mao, X. Yang, D. Wang, L. Zhang, Y. Bai, J. Bian, J. Long, F. Xie, H. Huang, X. Sang, H. Zhao
Journal: Annals of Oncology (2019)
Abstract 2537: Targeting chromosomal passenger complex by disruption of INCENP function inhibits tumor progression in neuroblastoma
Authors: Ming Sun, Veronica Veschi, Norris Lam, Sukriti Bagchi, Man Xu, Arnulfo Mendoza, Zhihui Liu, Carol J. Thiele
Journal: Cancer Research (2019)

Abstract Chromosomal passenger complex (CPC), which is composed of Aurora B and Survivin, INCENP and Borealin, regulates crucial mitotic events including chromosome alignment, segregation and cytokinesis during the mitosis. Disruption of CPC function by Aurora B and Survivin inhibition has been demonstrated to be effective at killing tumor cells and show promising results in many different cancer types including neuroblastoma (NB). However, chemical inhibition of either Aurora B or Survivin is unable to target CPC specifically due to off-target effects of Aurora B inhibitors on the other kinases and antiapoptotic activities of Survivin independent of this complex. In a chromatin-focused siRNA screen, we found that NB cells were particularly vulnerable to the silencing of INCENP, a gene encoding a key scaffolding and regulatory component of the CPC. In this study, we found that INCENP was highly expressed in NB cells and its expression levels were decreased upon Retinoic Acid (RA)-induced NB cell differentiation. Genetic silencing of INCENP reduced the growth of both MYCN single copy and MYCN amplified NB cell lines in vitro and led to significant decreases in NB xenograft growth and increases in murine survival in vivo. Elevated levels of INCENP were significantly associated with poor prognosis in primary NB tumors whereas low INCENP expression levels were predictive of better outcomes. Mechanistically, we found that INCENP depletion suppressed NB cell growth by inducing massive polyploidization, mitotic arrest, senescence and cell death (apoptosis). We also observed that in the majority of NB cell lines tested in vitro, cell death represented the primary cell fate after INCENP silencing due to a strong induction of DNA damage response and activation of the p53-p21 axis. Therefore, targeting INCENP phenocopies treatment with Aurora B inhibitor, providing a novel strategy to disrupt the activity of CPC and inhibit tumor progression in NB. Citation Format: Ming Sun, Veronica Veschi, Norris Lam, Sukriti Bagchi, Man Xu, Arnulfo Mendoza, Zhihui Liu, Carol J. Thiele. Targeting chromosomal passenger complex by disruption of INCENP function inhibits tumor progression in neuroblastoma [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 2537.
Abstract 4861: Chemotherapy improves overall survival in patients with T2N0M0 non-small cell lung cancer undergoing definitive radiation therapy: An analysis of the SEER database
Authors: Takefumi Komiya, Gerard Chaaya, Emily Powell
Journal: Cancer Research (2019)

Abstract Objectives: Despite relatively routine practice and recommendations by clinical guidelines, an advantage of adding systemic chemotherapy to definitive radiation in patients with early stage non-small cell lung cancer (NSCLC) has never been demonstrated by randomized or large-scale studies. This study evaluates the role of chemotherapy in addition to thoracic radiation in T2N0M0 NSCLC patients who did not undergo surgical resection. Materials and Methods: Using the Surveillance, Epidemiology, and End Results (SEER) database, we screened for patients with T2N0M0 NSCLC who received radiation therapy without surgical resection from 2004 to 2015. T-staging was defined according to the American Joint Committee on Cancer (AJCC) 6th (Year 2004+) and 7th(Year 2010+) versions. Kaplan-Meier curves and estimated overall survival according to chemotherapy status were determined by Log-rank test. Both univariate and multivariate analyses were conducted for the AJCC 6th (T2), 7th T2a, and 7th T2b groups. All the statistical analyses were performed using JMP software version 13 (SAS Institute, Cary, NC), and significance was achieved when P-value is below 0.05. Results: A total of 6,075 and 3,138 patients were identified for AJCC 6th (T2; 3cm -7cm) and 7th (T2a; 3 - 5cm, T2b; 5-7 cm) version, respectively. Administration of chemotherapy was associated with younger age, male sex, non-adenocarcinoma, and high pathologic grade. Kaplan-Meier estimates demonstrated that the chemotherapy group had a statistically significant longer five-year overall survival than the non-chemotherapy group in patients with AJCC 6th T2 (19.9% vs 15.8%, p=0.0023) and AJCC 7th T2b (5-7cm, 20.9% vs 13.6%, p=0.0046) but not those with AJCC 7th T2a (3-5cm, 24.3% vs 21.1%, p=0.4369). Multivariate analyses also revealed that the use of chemotherapy was an independent prognostic factor in AJCC 6th T2 and AJCC 7th T2b. Conclusions: This study strongly suggests that chemotherapy may benefit non-adenocarcinoma patients with primary tumor larger than 5cm (AJCC 8th T3) undergoing chest radiation. Citation Format: Takefumi Komiya, Gerard Chaaya, Emily Powell. Chemotherapy improves overall survival in patients with T2N0M0 non-small cell lung cancer undergoing definitive radiation therapy: An analysis of the SEER database [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 4861.
Abstract 2283: Accurate and efficient Next-Generation Sequencing approach for liquid biopsy detection and monitoring
Authors: Cai Chen, Christopher Kasbek, Yang Song, Si Chen, Nouran Almalki, Jiangyu Li, Yifei Wan, Jun Huang, Wei Ding
Journal: Cancer Research (2019)

Abstract Liquid biopsy detection using ctDNA has great potential in cancer diagnosis, monitoring, and predicting survival. However, detection sensitivity and specificity remain major challenge at the current stage. Here we utilized a targeted next-generation sequencing (NGS) approach to develop a noninvasive test to identify single nucleotide variations (SNVs), indels, fusions, copy number variations (CNVs) and microsatellite instability (MSI) present at low frequencies in different solid cancer patients. Target regions of interest were sequenced using tagging of individual molecules, followed by amplicon library generation and massive parallel sequencing using an Illumina platform. The variants were called and annotated using our in-house Actionable Genomic Interpretation System (AGIS) bioinformatics pipeline. This CLIA-approved NGS panel (LiquidGx™) detects more than 170 variants in 17 genes which were chosen mostly based on NCCN clinical actionable guidelines (AKT1, ALK, BRAF, EGFR, ERBB2, HRAS, KIT, KRAS, MAP2K1, MET, NRAS, PDGFRA, PIK3CA, PTEN, RET, ROS1 and TP53) with detection limit of 0.1%. Mutations are detected with 94% sensitivity and 99.8% specificity in a short turnaround time of 3-5 business days. To assess the performance in a clinical setting, accurate sequencing was performed on 210 lung cancer patients; the frequency of mutations identified of each gene closely mirrored the published lung cancer tissue biopsy data. Fusions are detected from exosomal RNA, which could increase the sensitivity and/or concordance to tumor. For spike-in data validation, the limit of detection (LOD) of CNV can reach 2.2 -2.5 total gene copies. In addition to actionable mutations for targeted therapy, LiquidGx™ provides MSI status, which can predict a predisposition to mutations as a result from impaired DNA mismatch repair (MMR) and help predict if a tumor will respond to anti-PD-1 therapy. The LOD of our MSI detection is 2-4%. In summary, we have developed a potent liquid biopsy platform for highly sensitive genomic biomarker test. Our technology is also available as an assay development service and can be easily adaptable to the diagnosis and monitoring of different cancer types. Note: This abstract was not presented at the meeting. Citation Format: Cai Chen, Christopher Kasbek, Yang Song, Si Chen, Nouran Almalki, Jiangyu Li, Yifei Wan, Jun Huang, Wei Ding. Accurate and efficient Next-Generation Sequencing approach for liquid biopsy detection and monitoring [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 2283.
Role of extra corporeal methods for light chain removal on renal recovery in multiple myeloma: A systematic review.
Authors: Hamza Hassan, Abdul Rafae, Nimra Iftikhar, fateeha furqan, Ahmad Iftikhar, Adeela Mushtaq, Afia Ashraf, Ammara Majeed, Sanjana Kashinath, Faryal Razzaq, Faiz Anwer
Journal: Journal of Clinical Oncology (2019)

e19530 Background: Renal impairment (RI) in Multiple Myeloma (MM) adversely affects the prognosis. Removing circulating free light chains via hemodialysis (HD) or plasma exchange (PLEX) along with chemotherapy can improve renal outcomes in MM. Methods: Per PRISMA guidelines a systematic search yielded 7311 articles since 2009 on 4 databases. After screening, 16 studies were included. Results: Main modalities were high cut off (HCO) HD, high flux (HF) HD, conventional HD and PLEX. N = 541 patients underwent HD/PLEX. 375/541 (69.3%) patients received HCO HD. In 2 RCTs, there was no significant difference in renal recovery (55.8% vs 51.6%; 41% vs 33%). The overall survival (OS) between the 2 groups was lower in the HCO group vs conventional HD (55.8% vs 76.6%) at 2 years while there was no significant difference in second study. Conclusions: HCO has failed to show promising efficacy with 2 RCTs failing to show statistical OS difference. There is paucity of data and further trials are needed. [Table: see text]
Abstract 14715: Higher Incidence of Ischemic and Bleeding Events in Pre-specified Registry Subset of Nobori Dual Antiplatelet Therapy as Appropriate Duration (NIPPON) Randomized Trial
Authors: Toshiro Shinke, Masato Nakamura, Raisuke Iijima, Junya Ako, Hisayuki Okada, Yoshiaki Ito, Kenji Ando, Hitoshi Anzai, Hiroyuki Tanaka, Yasunori Ueda, Shin Takiuchi, Yasunori Nishida, Hiroshi Ohira, Katsuhiro Kawaguchi, Makoto Kadotani, Hiroyuki Niinuma, Kazuto Omiya, Takashi Morita, Kan Zen, Yoshinori Yasaka, Kenji Inoue, Sugao Ishiwata, Masahiko Ochiai, Toshimitsu Hamasaki, Hiroyoshi Yokoi
Journal: Circulation (2017)

Introduction: A number of randomized trials have been conducted to explore the optimal duration of dual antiplatelet therapy (DAPT) after DES implantation. Mostly, however, observed event rate in p...
Abstract 5213: A modified L-penetratin peptide targeting e2f-1, 2 and 3 is effective in combination with cisplatin or pemetrexed against prostate and lung cancer cell lines
Authors: Gulam M. Rather, Michael Anyanwu, John E. Kerrigan, Kathleen W. Scotto, Olga Garbuzenko, Tamara Minko, Zoltan Szekely, Joseph R. Bertino
Journal: Cancer Research (2019)

Abstract Overexpression of the “activating” transcription factors, E2F1,2 and-3a induces genes involved in DNA synthesis and leads to cellular proliferation, tumor growth, and invasion. Therefore, inhibiting the overexpression of one or more activating E2Fs is a recognized target in cancer therapeutics. Dysregulation/overexpression of E2Fs is also controlled by deletion or mutations in the retinoblastoma protein in tumors. In our previous studies we showed that a novel penetratin conjugated 7-mer peptide (PEP) inhibited transcription of the E2F1, 2 and 3a by bounding tightly to E2F promoters. The PEP was cytotoxic at low micro molar concentrations to several malignant cell lines. As the PEP was unstable in vivo, the PEP was encapsulated in PEGylated liposomes (PL-PEP). Treatment of xenografts of the pRB negative small cell lung cancer H-69 and castrate resistant prostate cancer DU145 tumors propagated in mice with the PL- PEP, caused tumor regression. To increase stability and potency of the PEP, L-Arg in the PEP was replaced by D-Arg. Molecular simulation studies showed that the D-Arg PEP secondary structure is more stable than the L- Arg peptide structure in water. In vitro studies showed that the D-Arg PEP was more potent and more resistant to degradation by serum proteases than the L- form. As E2F is important for DNA repair, and for transcription of thymidylate synthase, we tested the effects of the PEP in combination with cisplatin, a DNA damaging drug and pemetrexed, a potent thymidylate synthase inhibitor. Combination studies of the D-ARG pep with cisplatin (in DU145, PC3, LnCap and 4T1) cells and with pemetrexed (in non-small cell lung cancer, H2009, H441, H1975 and H2228) resulted in synergistic cytotoxicity as determined by Chou-Talalay analysis. Citation Format: Gulam M. Rather, Michael Anyanwu, John E. Kerrigan, Kathleen W. Scotto, Olga Garbuzenko, Tamara Minko, Zoltan Szekely, Joseph R. Bertino. A modified L-penetratin peptide targeting e2f-1, 2 and 3 is effective in combination with cisplatin or pemetrexed against prostate and lung cancer cell lines [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 5213.
До питання диференціальної діагностики синдромів мальабсорбції (лактазна недостатність, непереносимість глютену, целіакія)
Authors: D.I. Kvit, T.Z. Marchenko, Ya.V. Tomkiv, H.Z. Vivcharivska, V.D. Shaidych, L.V. Zastavna, L.M. Horaiska, L.P. Sakalosh, Z.V. Tomkiv
Journal: GASTROENTEROLOGY (2020)

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