tbuckley/cabot-search huggingface dataset:
Knockdown of TPPP3 to inhibit cell proliferation and invasion in human colorectal cancer.
Authors: Yintao Li, Jinming Yu
Journal: Journal of Clinical Oncology (2017)

e23006 Background: Tubulin Polymerization Promoting Protein Family Member 3, TPPP3, a member of the TPPP protein family, has been reported to play important roles in initiation and progression of human cancers, such as lung cancer. However, the expression and underlying function of TPPP3 in colorectal cancer (CRC) have not yet been fully clarified. Methods: In this study, the mRNA and protein levels of TPPP3 in 96 clinical CRC specimens were determined by RT-PCR and immunohistochemistry. The relation between TPPP3 expression and clinicopathologic characteristics and overall survival (OS) were evaluated. TPPP3 was stably knockdowned by shRNA. In addition, CCK-8、Colony formation、Flow cytometric、Transwell and Angiogenesis assay were to examine the biological function of TPPP3 in CRC cells in vitro. Results: We show that TPPP3 was significantly increased in CRC tissues and associated with aggressive factors and poor patient survival. Further experiments showed that knockdown of TPPP3 inhibited cell proliferation, migration and invasion and induced cell apoptosis in vitro. In addition, TPPP3 silencing resulted in a decrease of angiogenesis and S phase fraction. And TPPP3 significantly affected the invasion and migration of CRC cells via the expression of MMP-9, Rac-1 and E-cadherin. Conclusions: Our results suggested that TPPP3 played an important role in CRC progress and might serve as novel therapeutic targets for CRC treatment.
Utilization of imaging during staging and surveillance of localized colon cancer in a large insured population.
Authors: Urshila Durani, Dennis Asante, Thorvardur Ragnar Halfdanarson, Herbert Heien, Lindsey R. Sangaralingham, Ronald S. Go
Journal: Journal of Clinical Oncology (2018)

6616 Background: It is unknown if staging and surveillance imaging in Stage I/II colon cancer are under- or over-utilized. On one hand, the Choosing Wisely campaign advocates against positron-emission tomography (PET) imaging and overzealous use of CT surveillance. Meanwhile, the NCCN recommends CT chest/abdomen/pelvis (CT C/A/P) at staging for Stage I/II colon cancer. For Stage II only, NCCN recommends surveillance CT C/A/P every 6-12 months for up to 5 years. Herein, we measure both underutilization and overutilization of staging and surveillance imaging in Stage I/II colon cancer. Methods: Insurance claims data from 2008-2016 were queried using OptumLabs (Cambridge, MA) for Stage I/II adult colon cancer patients who underwent surgery alone. Utilization of PET and CT C/A/P imaging was evaluated both during initial staging (N = 6,291) and surveillance for patients with at least 1 year of follow up (N = 5,466). Over-utilization was defined as (1) any usage of PET during staging or surveillance or (2) > 2 CT A/P or PET scans per year during surveillance. Results: Overall, 31% of Stage I/II colon cancer patients did not receive a staging CT A/P and 95% did not receive a CT chest on diagnosis. However, rates of staging CT A/P increased from 62% (2008) to 75% (2016) and rates of CT chest rose from 2.3% (2008) to 7.1% (2016). Use of PET imaging also increased slightly from 5.2% (2008) to 6.5% (2016) despite guidelines recommending against its use. On surveillance, 30% of patients with at least 1 year of follow up received a CT A/P or PET within the first year of surveillance. This dropped to 18% in year 2, 9% in year 3, 6% in year 4, and 3% in year 5 of follow up. Of patients who had surveillance CT A/P or PET, the proportion receiving > 2 scans within the first year (representing overutilization) declined from 32% (2008) to 10% (2016), p = 0.01. Conclusions: A large proportion of Stage I/II colon cancer patients do not receive appropriate staging CTs at diagnosis; however, the utilization of PET imaging at staging remains appropriately low. Furthermore, the vast majority of patients undergoing surveillance do not even receive 3 years of imaging follow-up. Among those who do receive surveillance imaging, overutilization has declined over time.
Environmental Chemicals in Breast Milk and Formula: Exposure and Risk Assessment Implications
Authors: Geniece M. Lehmann, Judy S. LaKind, Matthew H. Davis, Erin P. Hines, Satori A. Marchitti, Cecilia Alcala, Matthew Lorber
Journal: Environmental Health Perspectives (2018)

Background: Human health risk assessment methods have advanced in recent years to more accurately estimate risks associated with exposure during childhood. However, predicting risks related to infant exposures to environmental chemicals in breast milk and formula remains challenging. Objectives: Our goal was to compile available information on infant exposures to environmental chemicals in breast milk and formula, describe methods to characterize infant exposure and potential for health risk in the context of a risk assessment, and identify research needed to improve risk analyses based on this type of exposure and health risk information. Methods: We reviewed recent literature on levels of environmental chemicals in breast milk and formula, with a focus on data from the United States. We then selected three example publications that quantified infant exposure using breast milk or formula chemical concentrations and estimated breast milk or formula intake. The potential for health risk from these dietary exposures was then characterized by comparison with available health risk benchmarks. We identified areas of this approach in need of improvement to better characterize the potential for infant health risk from this critical exposure pathway. Discussion: Measurements of chemicals in breast milk and formula are integral to the evaluation of risk from early life dietary exposures to environmental chemicals. Risk assessments may also be informed by research investigating the impact of chemical exposure on developmental processes known to be active, and subject to disruption, during infancy, and by analysis of exposure–response data specific to the infant life stage. Critical data gaps exist in all of these areas. Conclusions: Better-designed studies are needed to characterize infant exposures to environmental chemicals in breast milk and infant formula as well as to improve risk assessments of chemicals found in both foods. https://doi.org/10.1289/EHP1953
Abstract 17725: Heart Failure in Women and Men During Acute Coronary Syndrome: interaction for Long-term Cardiovascular Mortality (The ABC-3 Study on Heart Disease)
Authors: Fiorella Cavuto, Giuseppe Berton, Francesco Bagato, Paola Michelazzo, Jessica Civiero, Rocco Cordiano, Beatrice Segafredo, Gerlando A Preti, Arianna Cati, Francesca Russo
Journal: Circulation (2016)

Introduction: Natural history studies have suggested important differences in survival between men and women in a broad spectrum of heart failure (HF) severity. Nonetheless, the relationship betwee...
Phase III study comparing gefitinib monotherapy (G) to combination therapy with gefitinib, carboplatin, and pemetrexed (GCP) for untreated patients (pts) with advanced non-small cell lung cancer (NSCLC) with EGFR mutations (NEJ009).
Authors: Atsushi Nakamura, Akira Inoue, Satoshi Morita, Yukio Hosomi, Terufumi Kato, Tatsuro Fukuhara, Akihiko Gemma, Kazuhisa Takahashi, Yuka Fujita, Toshiyuki Harada, Koichi Minato, Kei Takamura, Kunihiko Kobayashi, Toshihiro Nukiwa
Journal: Journal of Clinical Oncology (2018)

9005 Background: Although EGFR-TKI alone has been a standard first-line treatment for pts with advanced NSCLC with EGFR mutations, our phase II study (NEJ005) showed promising efficacy of GCP. NEJ009, an open-label, randomized phase III study, was conducted to evaluate the superiority of GCP vs G in progression-free survival (PFS), PFS2, and overall survival (OS). Methods: Pts with newly diagnosed stage III/IV/ recurrent NSCLC harboring an EGFR activating mutations (exon 19 deletion or exon 21 L858R) were randomized 1:1 to G 250 mg PO QD or GCP (G 250mg PO QD combined with carboplatin AUC 5 + pemetrexed 500mg/m2, every 3 weeks). The primary endpoints consisting of PFS, PFS2, and OS were sequentially analyzed according to a preplanned gate-keeping method. Secondary endpoints included objective response rate, safety, and quality of life. Results: In September 2017, a preplanned required number of events of PFS2 was observed. The ITT population included 344 pts with baseline characteristics fairly well balanced between the arms. Although GCP demonstrated significantly better PFS compared to G, there was no difference in PFS2 between the arms as below. Additional OS analysis (G:101 events vs GCP:83 events) revealed that median survival time of GCP was much longer than that of G (52.2 months vs 38.8 months, HR:0.695, p = 0.013). Conclusions: NEJ009 was the first phase III study which evaluated the efficacy of a combination of EGFR-TKI and platinum doublet chemotherapy in untreated advanced NSCLC pts with EGFR mutations. Although GCP regimen failed to demonstrate its superiority in PFS2, it may increase long survivors. ITT Population GCP (N = 169) G (N = 172) Median (months) Median (months) HR PFS 20.9 11.2 0.493 [95%CI: 18.0, 24.2] [95%CI: 9.0, 13.4] [95%CI: 0.390, 0.623] P < 0.001 PFS2 20.9 21.1 0.891 [95%CI: 18.0, 24.2] [95%CI: 17.9, 24.9] [95%CI: 0.708, 1.122] P = 0.806.
TCT-526 Long-Term Biocompatibility of a Novel Bioresorbable Scaffold for Peripheral Arteries: A Preliminary Study in Yucatan Miniswine
Authors: Marco Ferrone, Gilberto Melnick, Nicolas Isaza, Yanping Cheng, Gerard Conditt, Serge Rousselle, Juan Granada, Grzegorz Kaluza
Journal: Journal of the American College of Cardiology (2018)
Outcome driven persona-typing for precision oncology: Beyond a genomics centered view of individualized therapy.
Authors: Emanuel Petricoin, Subha Madhavan, R Joseph Bender
Journal: Journal of Clinical Oncology (2018)

4130 Background: Precision oncology is currently being defined mainly by a genomics-oriented view to tumor biology. However, a multi-omic view to tumor biology and more accurate outcome prediction is emerging. Combining this with treatment history, clinical-epidemiological data, and outcomes data may provide patient-specific descriptors that in N-dimensional space constitute population based “personas” that share common outcome destinies and identify response predictors to any given therapy. Methods: We utilized our database from 919 pancreatic adenocarcinoma patients within our ongoing registry study as a feasibility study. Commercial exome (315 genes by NGS) and proteomic data (24 proteins by IHC) as well as previous and current treatment history, epidemiological data and outcomes data were collected on every patient. Overall Survival (OS) was calculated and 10 individual outcome “personas” were created that spanned short-term survival ( < 6 months) to long term survival (32-110 months). Statistical analysis of individualized gene, protein, specific treatment type, disease stage, location, age, gender, ethnicity, was used to determine key principal components that significantly (p < 0.05) described each outcome persona to create a unique persona-type identifier. Results: Proteomic information was significantly associated with outcomes more frequently then genomic information (p = 0.02). Longest term outcome personas (OS > 32 months) were characterized by increased PD1 and decreased TS protein levels along with increased frequency of BRCA2 genomic alterations and treatment with off-label targeted therapy. Shorter term personas (OS < 6 months) were described by high TS protein levels along with genetic alterations in MYCL1, MYST3, VEGFA, ZNF703 and KEL. Conclusions: Persona-typing can be used to define and map key characteristics that associate with outcome and specific treatment. In the future, individual patients can be mapped to pre-defined personas that could more accurately describe outcome destiny and optimized/personalized therapy options.
A pilot trial of irinotecan, temozolomide and bevacizumab (ITB) for treatment of newly diagnosed patients with desmoplastic small round cell tumor (DSRCT).
Authors: Heather D. Magnan, Anita Price, Alexander J. Chou, Elyn Riedel, Leonard H. Wexler, Srikanth R. Ambati, Emily Kanaya Slotkin, Gary Ulaner, Shakeel Modak, Michael P. La Quaglia, Paul A. Meyers
Journal: Journal of Clinical Oncology (2017)

11050 Background: DSRCT is a rare tumor with a dismal prognosis in the setting of current treatment options. Preclinical data suggested that VEGF-dependent angiogenesis is important for DSRCT tumor biology and that targeting angiogenesis with bevacizumab in combination with irinotecan was more effective than treatment with irinotecan alone. This pilot study was designed to explore the safety and feasibility of adding ITB to the existing “P6- like” regimen used to treat DSRCT. Methods: Fifteen patients with newly diagnosed DSRCT were enrolled onto this single-institution study. They began treatment with 2 cycles of irinotecan (20 mg/m2/dose x 10 days) and temozolomide (100 mg/m2/dose x 5 days). Bevacizumab 10 mg/kg q2 weeks was added after sufficient time had passed from initial biopsy or surgery. Patients were then treated with cycles of alkylator based chemotherapy (3 cycles of cyclophosphamide, doxorubicin, vincristine and 3 cycles of ifosfamide, etoposide). An initial surgical resection was performed after cycle 5 and a second resection or second look surgery after cycle 8. Toxicity was graded according to CTCAE v.4.0. Secondary efficacy objectives were assessed using RECIST 1.1 criteria and the Kaplan Meir method. Results: 14 of 15 patients completed planned protocol therapy. One patient was taken off study due to complications associated with surgery after cycle 5 of chemotherapy. Stopping rules for unacceptable toxicity were not met. No patients experienced toxicity attributed to bevacizumab, and surgical morbidity was no greater than expected. Grade 3 diarrhea associated with irinotecan was experienced by 2 patients. Expected toxicities with “P6-like” cycles included grade 3/4 hematologic toxicity and admissions for febrile neutropenia in all patients. Response rate to the ITB cycles was 27% (95% CI 8-55%) and to the 5 pre-resection cycles was 73% (95% CI 45-92%). Median time to progression was 18.1 months. Overall survival at 1 year was 100% and 3 years 61% (95% CI 25-84%). Conclusions: The combination of ITB is active in patients with DSRCT, and it is feasible to combine these agents with standard chemotherapy without greater than expected toxicity. Clinical trial information: NCT01189643.
Quality of life and satisfaction with care in a contemporary cohort of pancreatic cancer patients.
Authors: Omar Abdel-Rahman, Daniel John Renouf, David F. Schaeffer, Winson Y. Cheung
Journal: Journal of Clinical Oncology (2017)

e21623 Background: Pancreatic cancer patients face significant disease- and treatment-related morbidity while management is frequently complex. With recent advances in radiation and surgery and the introduction of new systemic therapy regimens, understanding these patients’ quality of life (QOL) and their satisfaction with the care that they currently receive is essential to inform the design of future care delivery models. Methods: Pancreas Centre BC was established in British Columbia in 2012 to promote efficient triage, rapid access to multidisciplinary care, and early involvement of palliative care, if necessary. Consecutive pancreatic cancer patients who were referred to and seen at Pancreas Centre BC completed the EORTC-QLQ C30 and PAN26 questionnaires before and after surgery as well as surveys focused on the levels of satisfaction with their disease management. Using independent samples t-tests, we correlated clinical characteristics with QOL and satisfaction scores. Results: In total, 167 patients were included: median age was 63 years, 45% were men, and 70% were ECOG 0/1. The majority had early stage disease (78%), pancreatic head tumors (53%), adenocarcinoma histology (68%), and adjuvant gemcitabine (75%). Baseline mean QOL scores were 63, 90, 83, 58 and 92 (out of 100) in the overall, physical, emotional, cognitive and social domains, respectively. Advanced age ( &gt; 70 years), weight loss ( &gt; 10 kg), and poor ECOG were independently associated with lower overall QOL rating (all p &gt; 0.05). Surgery had a positive impact on all functional domains where we observed a mean improvement in QOL scores ranging from 8 to 17 points (all p &gt; 0.05). In terms of satisfaction, 94% of patients rated their overall care as good to excellent. Likewise, 80% of patients were very or mostly satisfied with the amount of information they received and 84% of patients rated the healthcare information they received as very or mostly helpful. Conclusions: Despite the morbidity of pancreatic cancer, patients referred to and seen at a tertiary pancreatic cancer center reported good QOL and satisfaction levels, suggesting that the centralization of pancreatic cancer care may be an effective model to address the high priority needs of this population
TCT-504 Incidence and natural course of incomplete stent apposition in heavily calcified lesions requiring rotational atherectomy prior to stenting: an optical coherence tomography study
Authors: Atsushi Kyodo, Hiroyuki Okura, Saki Iwai, Akihiko Okamura, Daisuke Kamon, Yukihiro Hashimoto, Tomoya Ueda, Tsunenari Soeda, Makoto Watanabe, Yoshihiko Saito
Journal: Journal of the American College of Cardiology (2018)
Expanded molecular routine testing for targetable mutations in non-small cell lung cancer to reveal frequent co-occuring mutations.
Authors: Anna Kostenko, Jana Fassunke, Susanne Steinhauser, Matthias Scheffler, Sabine Merkelbach-Bruse, Sebastian Yves Friedrich Michels, Rieke Nila Fischer, Lucia Nogova, Martin Hellmich, Thomas Zander, Reinhard Buettner, Juergen Wolf
Journal: Journal of Clinical Oncology (2017)

e20596 Background: Using next-gen sequencing of predefined gene panels in routine clinical diagnostics of lung cancer allows, in contrast to single-gene assays, assessment of co-occuring mutations, which might underly heterogeneity of response to targeted drugs and survival. The Network Genomic Medicine (NGM) performs high sensitive next generation sequencing (NGS) based routine molecular diagnostics on a central platform for about 5000 inoperable lung cancer patients (pts) annually in Germany. Methods: NGS panel used in NGM consists of 17 genes to cover potentially targetable aberrations. Mutation analyses were run on an Illumina (MySeq) platform, while FISH analyses were performed separately. In 2016, we have started the evaluation of all NGM pts with available clinical data who had received NGS-based molecular diagnostics. In particular, we have focused on non-squamous (non-sq) and squamous (sq) NSCLC pts with co-occurring mutations: their frequency, significance and impact on overall survival. Results: From 2014 molecular genotyping was performed for 7,893 NGM pts (n = 7,246 NSCLC (5,667 non-sq and 1,487 sq pts) and n = 489 SCLC) with eligible clinical data. Genetic alterations in transformation-associated pathways were found in 79 % of all NSCLC pts. Furthermore, co-occurring mutations were detected in 39 % of these pts: 40 % in non-sq and 37 % in sq NSCLC. 11 % of pts had more than 2 co-occurring mutations. 1 % of all pts had 5 co-occurring mutations. The most frequent paired mutations were KRAS, EGFR and MET each with TP53 in non-sq and FRGF1 and TP53 in sq NSCLC. The incidences and significance of 3, 4 and 5 co-mutations as well as the impact of these co-occurring mutations on overall survival will be presented. Conclusions: Frequent occurrence of co-occuring mutations in transformation – associated pathways underlines the genetic heterogeneity also of lung cancer with classical driver mutation and the impact of co-occurring mutations on survival. This work confirms the use of molecular multiplex testing in routine molecular diagnostics of NSCLC. Assessment of co-occuring mutations will help to further specify genetically defined subgroups of lung cancer with therapeutic relevance.
Circulating Extracellular Vesicles in Human Disease
Authors: Ravi Shah, Tushar Patel, Jane E. Freedman
Journal: New England Journal of Medicine (2018)

Interview with Dr. Tushar Patel on the role of extracellular vesicles in physiologic function and as potential biomarkers for disease. (08:09)Download Circulating extracellular vesicles, which are produced by normal and diseased tissues and released into body fluids, can be markers of disease processes and perhaps even tools to deliver new therapies.
Phase II study of perioperative combination chemotherapy with triweekly carboplatin and weekly dose dense paclitaxel and radical hysterectomy for locally advanced cervical cancer (SGSG-016 study).
Authors: Shoji Nagao, Ai Kogiku, Michiko Nonaka, Yuko Shiroyama, Tetsuro Oishi, Satoshi Yamaguchi, Kazuhiro Takehara, Muneaki Shimada, Junzo Kigawa
Journal: Journal of Clinical Oncology (2017)

e17022 Background: The primary objective of this study was to assess efficacy and safety of triweekly carboplatin plus weekly dose dense paclitaxel (ddTC therapy) before and after radical hysterectomy without radiotherapy (RH) for women with locally advanced cervical cancer. Methods: Patients with FIGO stage IB2, IIA2, or IIB cervical cancer received 3 cycles of carboplatin at an area under the curve of 6 on day 1 and paclitaxel at 80mg/m 2 on day 1, 8, and 15 every 21 days followed by RH. Patients with one or more high-risk factors for recurrence including lymph vascular invasion, parametrial invasion, lymph node matastasis, or positive margin received additional 3 cycles of ddTC therapy after RH. Results: Between September 2014 and July 2016, 50 women including 13 with FIGO stage Ib2, 5 with stage IIa2, and 32 with stage IIb were enrolled in this study. There were 37 squamous cell carcinoma, 10 adenocarcinoma, 2 adenosquamous carcinoma, and 1 large cell neuroendocrine carcinoma. Median age was 46 years (range 30-78). Forty-three women (86%) completed planed 3 cycled of chemotherapy before surgery. The overall response rate was 92% (18 complete response, 28 partial response, 3 stable disease, 1 progressive disease). Forty-nine patients (98%) completed planed radical hystsrectomy, but a patient with invasion to bladder musculature received concurrent radiation therapy instead of surgery. Eleven patients (22%; 10 with SCC, 1 with large cell neuroendocrine carcinoma) achieved pathological complete response. Eleven other patients with one or more high-risk factors received 3 cycles of ddTC therapy after surgery. Grade 3/4 hematological toxicities included neutrocytopenia (58%), thrombocytopenia (2%) and anemia (24%). One patients experienced neutropenic fever. Grade 3/4 non-hematological toxicities were observed in 4 patients (1, grade 3 nausea; 1, grade3 carboplatin allergy; 1, grade 3 paclitaxel allergy; 1 grade 3 elevetaed liver enzyme). Conclusions: Administration of ddTC therapy before and after RH has good efficacy and acceptable toxicity in women with locally advanced cervical cancer. Clinical trial information: UMIN000024136.