tbuckley/cabot-search huggingface dataset:
Effects of oxaliplatin, capecitabine and irinotecan (OXIRI) on pancreatic ductal adenocarcinoma cell lines carrying different <i>Kras</i> mutational status.
Authors: Balram Chowbay, Jing Xiang Gimson Wong, Charlie Marvalim, Shu Ling Ng, Natalia Sutiman, Wai Fook Leong
Journal: Journal of Clinical Oncology (2016)

e15722 Background: Gemcitabine plus erlotinib (G+E) is the standard of care for treatment of patients with pancreatic ductal adenocarcinoma (PDAC). The FOLFIRINOX regimen was shown to significantly improve the survival of PDAC patients over gemcitabine but occurred at the expense of significant toxicities, highlighting the crucial need for more effective treatment options that are tolerable. This study sought to investigate the effects of oxaliplatin, xeloda and irinotecan (OXIRI) regimen versus the G+E regimen in PDAC cell lines. Methods: The anti-proliferative effects of the drug combinations were analyzed in a panel of human PDAC cell lines, BxPC3 (KRASWT), PANC-1 (KRASG12D), MIAPaCa-2 (KRASG12C) and AsPC-1 (KRASG12D) (ATCC). Cells were treated at the following concentrations: oxaliplatin (0.0001 nM - 100 uM), SN-38 (0.00001 nM - 10 uM), 5-FU (0.0001 nM - 100 uM), gemcitabine (0.001 nM - 100 uM) and erlotinib (0.001 nM - 10 uM) and cell viability was assessed using the CCK-8 assay 72 hours after drug treatments. Cell cycle and apoptosis analyses were performed using FITC BrdU Flow Kit and Annexin V-FITC Assay, respectively, and results analyzed using FACSDiva v6.1.2. Results: As single agents, all four PDAC cells lines were most sensitive to oxaliplatin and least sensitive to erlotinib. The OXIRI regimen was more effective than gemcitabine alone, as well as the G+E regimen in inhibiting cell proliferation across all the four cell lines. At clinically relevant concentrations of oxaliplatin 10 uM, 5-FU 10 uM and SN-38 1 uM, greater than 90% growth inhibition was achieved in BxPC-3 and MIA PaCa-2 cells and greater than 80% inhibition was achieved in PANC-1 and AsPC-1 cells. In contrast, treatment with gemcitabine 100 uM and erlotinib 1-10 uM only resulted in approximately 50% growth inhibition in MIA PaCa-2, PANC-1 and AsPC-1 cells, and 67% growth inhibition in BxPC-3 cells. Notably, evidence of marked G2-M and S phase arrest and increased apoptosis were observed across all four cell lines treated with the OXIRI regimen. Conclusions: These findings suggest that the OXIRI regimen exhibits greater anti-cancer effects than the combination of gemcitabine and erlotinib in PDAC cell lines.
Dysregulation of RUNX2/Activin-A Axis upon miR-376c Downregulation Promotes Lymph Node Metastasis in Head and Neck Squamous Cell Carcinoma
Authors: Wei-Min Chang, Yuan-Feng Lin, Chia-Yi Su, Hsuan-Yu Peng, Yu-Chan Chang, Tsung-Ching Lai, Guan-Hsun Wu, Yuan-Ming Hsu, Li-Hsing Chi, Jenn-Ren Hsiao, Chi-Long Chen, Jang-Yang Chang, Yi-Shing Shieh, Michael Hsiao, Shine-Gwo Shiah
Journal: Cancer Research (2016)

Abstract Epigenetic correlates of the head and neck cancer may illuminate its pathogenic roots. Through a gene set enrichment analysis, we found that the oncogenic transcription factor RUNX2 is widely upregulated in the head and neck squamous cell carcinoma (HNSCC) with lymph node metastasis, where it also predicts poor prognosis in patients with HNSCC. Enforced expression of ectopic RUNX2 promoted the metastatic capabilities of HNSCC, whereas RUNX2 silencing inhibited these features. Mechanistic investigations showed that manipulating levels of activin A (INHBA) could rescue or compromise the RUNX2-mediated metastatic capabilities of HNSCC cells. Furthermore, we found that miR-376c-3p encoded within the 3′-untranslated region of RUNX2 played a pivotal role in regulating RUNX2 expression in highly metastatic HNSCC cells, where it was downregulated commonly. Restoring miR-376c expression in this setting suppressed expression of RUNX2/INHBA axis along with metastatic capability. Clinically, we observed an inverse relationship between miR-376c-3p expression and the RUNX2/INHBA axis in HNSCC specimens. In summary, our results defined a novel pathway in which dysregulation of the RUNX2/INHBA axis due to miR-376c downregulation fosters lymph node metastasis in HNSCC. Cancer Res; 76(24); 7140–50. ©2016 AACR.
Response to Comment on Fischer et al. Text Message Support for Weight Loss in Patients With Prediabetes: A Randomized Clinical Trial. Diabetes Care 2016;39:1364–1370
Authors: Henry H. Fischer, Rocio I. Pereira, Susan L. Moore, Michael J. Durfee, Jeanne M. Rozwadowski, Edward P. Havranek
Journal: Diabetes Care (2016)

We thank Afarideh et al. (1) for their thoughtful discussion of our study of text message support for weight loss in patients with prediabetes (2). We agree that the differential impact by language of the text message intervention was striking and merits further exploration. In a separate article, we will analyze in detail our end-study focus groups and survey data as well as comorbidities and characteristics across our cohorts to further evaluate our study findings, including the greater weight loss observed among participants in the Spanish group.

Afarideh et al. question whether some of the differences between the English- and Spanish-speaking groups in baseline demographics (more women in Spanish intervention group), clinical metrics (mean HbA1c of 6.0% vs. 5.8% and …
Phase II trial of imatinib (I) and docetaxel (D) in recurrent non-small cell lung cancer (NSCLC)
Authors: C. H. Huang, S. Williamson, P. J. Van Veldhuizen, C. T. Hsueh, H. Smith, M. Mayo, A. Allen, K. Kelly
Journal: Journal of Clinical Oncology (2007)

18132 Background: Second line monotherapy for NSCLC produces a response rate of 9% and a median survival of 7–8 months, regardless of the agent used. Emerging data suggest that combining an approved agent with an anti-angiogenesis inhibitor may improve efficacy in the salvage setting. Platelet Derived Growth Factor Receptor alpha (PDGFR-alpha) is involved in angiogenesis and its expression has been reported in 100% of adenocarcinoma (11/11) and 89% of squamous cell (16/18) lung cancer specimens in a small group sample. Preclinical models have shown that I inhibits PDGFR and may subsequently inhibit angiogenesis. In addition, I + D have additive anticancer activity. We initiated a phase II trial of I +D to evaluate the efficacy and safety of this combination regimen in recurrent NSCLC. Methods: Patients (pts)with pathologically confirmed NSCLC, measurable disease, no more than 1 previous platinum-based chemotherapy regimen, PS 0–1, clinically stable brain metastases and adequate organ function were eligible. Tumor samples, when available, were tested for PDGFR expression by immunohistochemistry. All pts received D 30mg/m2 intravenously weekly x 3 every 4 weeks and oral I 600mg daily for 4 cycles. Non- progressors after 4 cycles continued with I alone for a total of 12 months or until progression. Tumor response was assessed every 2 cycles. The primary endpoint was response rate. A Simon two-stage design was used with 16 patients in the first stage and accrual of a total of 32 patients planned. Results: Currently 15/16 patients for stage I of the protocol have been enrolled. A total of 24 cycles of combined I+D were given. Patient characteristics and toxicity data are described in the table below. Efficacy data is premature. Conclusion : I +D combination has been well tolerated in this relapsed population. A detailed toxicity, efficacy and PDGFR analysis will be presented. [Table: see text] No significant financial relationships to disclose.
Abstract 358: Intracellular Ca2+ Can Directly Regulate NaV1.5 Through An Efl Motif In The Absence Of Calmodulin Binding.
Authors: Subrata Biswas, Deborah DiSilvestre, YanLi Tian, Victoria L Halperin, Gordon Tomaselli
Journal: Circulation (2007)

Intracellular Ca2+ regulates gating of voltage-dependent cardiac sodium channels (NaV1.5). The roles of the calmodulin (CaM) binding IQ motif and the upstream EF-hand like (EFL) motif in C-terminus...
GW26-e4408 The protective effects of salidroside from exhaustive exercise-induced heart injury by enhancing the PGC-1α–NRF1–NRF2 pathway and mitochondrial respiratory function in rats
Authors: Zheng Ping, Xuejiao Li, Yujuan Cui, Longfei Zhang, Xuebin Cao
Journal: Journal of the American College of Cardiology (2015)
Clinical Implications of Brief Device-Detected Atrial Tachyarrhythmias in a Cardiac Rhythm Management Device Population
Authors: Steven Swiryn, Michael V. Orlov, David G. Benditt, John P. DiMarco, Donald M. Lloyd-Jones, Edward Karst, Fujian Qu, Mara T. Slawsky, Melanie Turkel, Albert L. Waldo
Journal: Circulation (2016)

Background: The RATE Registry (Registry of Atrial Tachycardia and Atrial Fibrillation Episodes) is a prospective, outcomes-oriented registry designed to document the prevalence of atrial tachycardia and/or fibrillation (AT/AF) of any duration in patients with pacemakers and implantable cardioverter defibrillators (ICDs) and evaluate associations between rigorously adjudicated AT/AF and predefined clinical events, including stroke. The appropriate clinical response to brief episodes of AT/AF remains unclear. Methods: Rigorously adjudicated electrogram (EGM) data were correlated with adjudicated clinical events with logistic regression and Cox models. Long episodes of AT/AF were defined as episodes in which the onset and/or offset of AT/AF was not present within a single EGM recording. Short episodes of AT/AF were defined as episodes in which both the onset and offset of AT/AF were present within a single EGM recording. Results: We enrolled 5379 patients with pacemakers (N=3141) or ICDs (N=2238) at 225 US sites (median follow-up 22.9 months). There were 359 deaths. There were 478 hospitalizations among 342 patients for clinical events. We adjudicated 37 531 EGMs; 50% of patients had at least one episode of AT/AF. Patients with clinical events were more likely than those without to have long AT/AF (31.9% vs. 22.1% for pacemaker patients and 28.7% vs. 20.2% for ICD patients; P &lt;0.05 for both groups). Only short episodes of AT/AF were documented in 9% of pacemaker patients and 16% of ICD patients. Patients with clinical events were no more likely than those without to have short AT/AF (5.1% vs. 7.9% for pacemaker patients and 11.5% vs. 10.4% for ICD patients; P =0.21 and 0.66, respectively). Conclusions: In the RATE Registry, rigorously adjudicated short episodes of AT/AF, as defined, were not associated with increased risk of clinical events compared with patients without documented AT/AF. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT00837798.
Phase-2 Study of Pomalidomide in Advanced Corticosteroid-Resistant Chronic Graft-Versus-Host Disease (cGVHD).
Authors: Iskra Pusic, John F. DiPersio, Stefanie L Goran, Edie M Romvari, Stephanie L Bauer, Holly S Comer, Camille N. Abboud, Amanda F Cashen, Robert Peter Gale, Steven Z. Pavletic
Journal: Blood (2009)
Rapid Reduction of Light-Chains and Proteinuria in Multiple Myeloma (MM) Patients with Light Chain Induced Acute Renal Failure Treated with Lenalidomide and Dexamethasone
Authors: Heinz Ludwig, Josef Thaler, Jan Koren, Ludek Pour, Ercan Müldür, Martin Schreder, Niklas Zojer, Adalbert Weissmann, Zdenek Adam
Journal: Blood (2011)
Presentation of metastatic prostate cancer in the post-PSA era.
Authors: R. J. Dickstein, J. A. Nabhani, J. E. Kreshover, M. H. Katz, G. Gignac
Journal: Journal of Clinical Oncology (2010)

e15064 Background: Metastatic prostate cancer (MPC) has a variable in presentation. We identified two groups of patients with MPC; those with metastatic disease at the time of initial diagnosis and those who progressed from localized disease. We sought to identify differences in clinical, pathologic, socioeconomic factors, and survival metrics between the two cohorts. Methods: We identified patients with MPC from 2003 to 2008 at a single institution. Patient related factors [age, grade, prostate specific antigen (PSA), digital rectal exam (DRE), radiographic findings, family history, age-adjusted Charlson comorbidity index (CCI), body mass index (BMI), and smoking history], demographic and socioeconomic factors (ethnicity/race and insurance status) and survival outcomes (1-year and time from metastases to death) were compared between the two cohorts using a two sided student's t-test and test of proportions. Results: Seventy patients developed MPC an average of 6.7 years (0.5-20.5) after being initially diagnosed with localized disease and 100 patients had metastases at initial presentation. Statistically, there were differences in patient related factors between the patients who progressed to as opposed to presented with metastases including the following: older age (71.7 vs 67.1 years), lower grade disease (3.7 vs 4.1 primary Gleason score and 7.6 vs 8.2 Gleason sum), decreased proportion with an abnormal DRE (72.9 vs 86.1%), and a higher CCI (4.79 vs 4.22). There was no difference in demographic or socioeconomic factors between the two cohorts. Thirty five patients who presented with metastases and 24 patients who progressed from localized disease died during the study period; however, there was no difference in survival outcomes between the two groups (807.3 vs 866.3 days). Conclusions: There are very few differences between patients who present with MPC at the time of diagnosis and those who progress from localized disease. Patients who present with MPC at initial diagnosis appear to be younger, have higher grade disease, and less comorbid disease than those progressing to metastatic cancer. However, once metastases have developed, our analysis suggests that there is no survival difference, regardless of the factors leading to the diagnosis. No significant financial relationships to disclose.
Oncogenic events rather than antigen selection pressure may be the main driving forces for relapse in diffuse large B‐cell lymphomas
Authors: David Rizzo, Pierre‐Julien Viailly, Sylvain Mareschal, Elodie Bohers, Jean‐Michel Picquenot, Dominique Penther, Sydney Dubois, Vinciane Marchand, Philippe Bertrand, Catherine Maingonnat, Pascaline Etancelin, Jean Feuillard, Christian Bastard, Hervé Tilly, Fabrice Jardin, Philippe Ruminy
Journal: American Journal of Hematology (2016)

Little is known on the phylogenetic relationship between diagnostic and relapse clones of diffuse large B-cell lymphoma (DLBCL). We applied high throughput sequencing (HTS) of the VDJ locus of Immunoglobulin heavy chain (IGHV) on 14 DLBCL patients with serial samples, including tumor biopsies and/or peripheral blood mononuclear cells (PBMC). Phylogenetic data were consolidated with targeted sequencing and cytogenetics. Phylogeny clearly showed that DLBCL relapse could occur according either an early or a late divergent mode. These two modes of divergence were independent from the elapsed time between diagnosis and relapse. We found no significant features for antigen selection pressure in complementary determining region both at diagnosis and relapse for 9/12 pairs and a conserved negative selection pressure for the three remaining cases. Targeted HTS and conventional cytogenetics revealed a branched vs. linear evolution for 5/5 IGHV early divergent cases, but unexpected such "oncogenetic" branched evolution could be found in at least 2/7 IGHV late divergent cases. Thus, if BCR signaling is mandatory for DLBCL emergence, oncogenetic events under chemotherapy selection pressure may be the main driving forces at relapse. Finally, circulating subclones with divergent IGHV somatic hypermutations patterns from initial biopsy could be detected in PBMC at diagnosis for 4/6 patients and, for two of them, at least one was similar to the ones found at relapse. This study highlights that oncogenetic intraclonal diversity of DLBCL should be evaluated beyond the scope a single biopsy and represents a rationale for future investigations using peripheral blood for lymphoid malignancies genotyping. Am. J. Hematol. 92:68-76, 2017. © 2016 Wiley Periodicals, Inc.
Rituximab maintenance therapy (RM) for relapsed/refractory follicular lymphoma (FL): Long-term economic impact in the French setting
Authors: P. Brice, H. Miadi-Fargier, C. Le Pen, A. Pacull, C. Coudray-Omnes, E. Deconinck
Journal: Journal of Clinical Oncology (2007)

8076 Background: FL in advanced stages is a life-threatening chronic disease. As recently demonstrated in the pivotal trial EORTC20981, RM significantly prolongs both progression free survival (PFS) and overall survival (OS) in relapsed/refractory FL patients responding to an induction treatment. Beyond these clinical benefits, the study objective was to assess, from the French Sickness Funds perspective, long-term costs and cost-effectiveness of RM after induction therapy versus current standard practice (observation). Methods: A lifetime transition model (30-years time horizon) with 3 health states (progression free, progressive disease and death) was developed comparing RM and observation (Obs). PFS and OS in the health states transition model were derived from the EORTC20981 trial with a median follow-up of 28 months. PFS and the OS benefits of RM therapy were conservatively assumed to last only 5 years. Standard French costs (2006 national tariffs) were applied to resources estimated from a prescription observational study, expert opinion and bibliography (in case of maintenance: acquisition and administration of RM, grade 3–4 adverse events, follow-up and in case of relapse: pre-treatment check- up, chemotherapy, radiotherapy, stem cell transplantation, adverse events, follow-up and supportive care). Costs were discounted at 3% and sensitivity analyses were performed. Results: RM is effective in the management of relapsed/resistant FL with more than one year of benefit in terms of survival. Patients receiving RM had a longer life expectancy than those with Obs (6.60 versus 5.41 years). Overall lifetime average costs were €71,314 and €62,251 respectively for RM and Obs. Incremental cost-effectiveness ratio (ICER) was €7,612 per life year gained, varying from €7,154 to €8,847 in one-way sensitivity analysis. This study did not include palliative care and productivity costs. As the relapse rate is lower in the RM group, those limitations are conservative. Conclusions: The economic assessment shows that RM is a cost-effective strategy in the management of relapsed/refractory FL in France with an ICER largely below the threshold commonly cited in such analysis. No significant financial relationships to disclose.
Autologous Hematopoietic Stem Cell Transplantationfor Adult with Acute Leukemia in First Complete Remission
Authors: Huifen Zhou, Wu Depei, Xiaowen Tang, Aining Sun, Zhengming Jin, Huiying Qiu, Miao Miao, Chengcheng Fu, Guangsheng He, Yue Han
Journal: Blood (2008)
Mature Results From ECOG Study E1405 – A Phase II Study of VcR-CVAD with Maintenance Rituximab for Previously Untreated Mantle Cell Lymphoma
Authors: Brad S. Kahl, Hailun Li, Mitchell R Smith, Randy D. Gascoyne, David T. Yang, Elisabeth Paietta, Ranjana H. Advani, Sandra J. Horning
Journal: Blood (2012)
Sensitive detection of CTCs in thoracic malignant tumors with a “universal” CTC-chip.
Authors: Kazue Yoneda, Yasuhiro Chikaishi, Eri Kawashima, Miyoko Takeshita, Kenichi Kobayashi, Rintaro Oyama, Sakiko Yura, Hiroki Matsumiya, Shuichi Shinohara, Taiji Kuwata, Masaru Takenaka, Soichi Oka, Ayako Hirai, Yuko Tashima, Naoko Imanishi, Koji Kuroda, Yoshika Nagata, Takashi Ohnaga, Fumihiro Tanaka
Journal: Journal of Clinical Oncology (2016)

e23045 Background: Circulating tumor cells (CTCs) are tumor cells shed from primary tumor and circulate in the peripheral blood. CTCs, as a surrogate of distant metastasis, can be potentially useful in diagnosis and monitoring therapeutic effects in malignant tumors. Among a variety of systems for detecting CTCs, the “Cellsearch”is the only system approved for clinical use. However, EpCAM-negative tumor cells, such as those originating from non-epithelial cells and those undergoing epithelial-mesenchymal transition (EMT) cannot be captured with the “CellSearch”that is an EpCAM-based separation system. Therefore, we have developed a novel polymeric microfluidic device (“universal” CTC-chip) that can capture CTCs positive or negative EpCAM expression (AACR 2015). In the present study, we examined CTCs-detection performance of the CTC-chip in patients with thoracic malignant tumors (lung cancer as an “EpCAM-positive” tumor and malignant pleural mesothelioma [MPM] as an “EpCAM-negative” tumor) in comparison with that of the CellSearch. Methods: TheCTC-chip, coated with an anti-EpCAM antibody, was used to capture CTCs in the blood samples (n = 11) from small cell lung cancer (SCLC) patients. To capture CTCs in the samples (n = 7) from MPM patients, the CTC-chip was coated with an antibody against podoplanin that is expressed on mesothelial cells. After immuno-staining for cytokeratin and CD45 on the chip, a captured cell containing Hoechst-positive nucleus and cytokeratin-positive/CD45-negative was judged as a CTC. The CTC-count for each sample was represented as the number per 7.5mL of the blood. Results: The median CTC-count detected with the CTC-chip in SCLC was 90 (range, 0-405), which was significantly higher than that (the median CTC-count, 0; range, 0-19) with the CellSearch (p < 0.01). In the peripheral blood sampled from MPM patients, CTC was not detected in any patient using the CellSearch, but was detected in all 7 patients with the median CTC-count of 383 (range 0-788). Conclusions: The “universal” CTC-chip achieved higher performance in detection of CTCs of thoracic malignant tumors as compared with the CellSearch.
Long-Term Engraftment and Self-Renewal of AML Stem Cells in the Newborn NOD-scid/IL2rgnull Immunodeficient Mouse Model.
Authors: Shuro Yoshida, Fumihiko Ishikawa, Masaki Yasukawa, Toshihiro Miyamoto, Goichi Yoshimoto, Noriaki Kawano, Kazuya Shimoda, Koichi Akashi, Leonard D. Shultz, Mine Harada
Journal: Blood (2005)
Characterization of ‘Early’ vs ‘Late’ Endothelial Progenitor Cells (EPCs) Which Are Derived from Human Umbilical Cord Blood (HCB) during Ex Vivo Expansion.
Authors: Eun-Sun Yoo, Jee-Young Ahn, Yun-Kyung Bae, Seung-Eun Lee, Sang min Lee, Yeung-Chul Mun, Kyung-Eun Lee, Chu-Myong Seong
Journal: Blood (2005)
Abstract C32: The function of GPR56 in metastasis formation of melanoma
Authors: Nancy Corson, Liquan Yang, Lei Xu
Journal: Cancer Research (2016)

Abstract Disseminated cancer cells often persist in tissues for a long period before being manifested as clinically detectable metastases. This metastasis dormancy imposes a main threat for cancer patients, especially after their first line of cancer treatment. Little is known as to how this dormancy is maintained and what triggers its awakening, but tumor microenvironment is thought to play a decisive role. We discovered that a member of newly described family of adhesion G protein-coupled receptors (GPCRs), GPR56, inhibits metastasis formation of melanoma cell lines and sequesters them at a dormant state in lung. GPR56 binds to TG2, a component in extracellular matrix (ECM) that could also function as a cross linking enzyme. It is significantly up-regulated in human melanoma metastases relative to the primary tumors and its expression promotes metastasis formation of melanoma cells in the experimental metastasis model. The down-regulation of TG2 by GPR56 may abolish the pro-metastasis function of TG2 in melanoma cells via destabilizing ECM and contribute to their sequestration at the dormant state. Furthermore, RNAseq analyses suggest that GPR56 may regulate the expression of factors involved in cellular homeostasis. It is thus possible that GPR56 maintains metastasis dormancy in melanoma by down-regulating TG2 in ECM and perturbing cellular homeostasis. Citation Format: Nancy Corson, Liquan Yang, Lei Xu. The function of GPR56 in metastasis formation of melanoma. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr C32.