tbuckley/cabot-search huggingface dataset:
Effect of apricoxib, a novel COX-2 inhibitor, on the efficacy of standard therapy in human pancreatic cancer cell lines in vitro and in vivo.
Authors: A. R. Kirane
Journal: Journal of Clinical Oncology (2011)

227 Background: Gemcitabine-erlotinib is standard of care (SOC) for pancreatic cancer, but this regimen can still be improved upon with regard to prolonging patient survival. Cyclo-oxygenase-2 (COX-2) is overexpressed in pancreatic cancer and implicated in pancreatic tumor progression. Inhibition of COX-2 decreases tumor growth, augments the activity of both gemcitabine and EGFR inhibition, and may play a role in preventing or reversing EMT. This study characterized the effects of COX-2 inhibition on pancreatic cancer cell lines and determined if the addition of apricoxib enhances sensitivity to chemotherapy. Methods: Baseline EGFR and COX-2 expression were determined in 7 human pancreatic cancer cell lines and functional responses measured by changes in phospho-EGFR (p-EGFR) and prostaglandin E 2 (PGE 2 ) production by ELISA. Cytotoxicity was determined for gemcitabine, erlotinib, and apricoxib independently and in combination by MTS assay. The effect of SOC therapy alone or in combination with 10 or 30 mg/kg apricoxib PO on AsPC-1 and Colo357 tumors in vivo was determined in SCID mice bearing established orthotopic xenografts. Tissue was analyzed by IHC and VEGF levels were determined by ELISA. Results: All lines expressed EGFR and COX-2, but expression alone was not predictive of p-EGFR level, PGE 2 production, or response to drug therapy. In vitro, AsPC-1 cells had negligible COX-2 activity, whereas Colo357 cells displayed high levels of COX-2 and PGE 2 production. Cell growth and COX-2 activity decreased in all cell lines in the presence of apricoxib and addition of apricoxib improved response to chemotherapy. In vivo, addition of apricoxib to SOC significantly reduced primary tumor growth and almost eradicated metastases in mice bearing Colo357 but not AsPC-1 xenografts. Plasma VEGF levels were unaltered by apricoxib treatment in AsPC-1-bearing animals but were suppressed to undetectable levels in Colo357-bearing animals. Markers of EMT were significantly decreased in animals treated with apricoxib. Conclusions: Apricoxib enhances the efficacy of gemcitabine and erlotinib in vitro and in vivo and warrants clinical evaluation in patients with pancreatic cancer. A phase II study is ongoing. No significant financial relationships to disclose.
Peripheral blood mRNA signature for colorectal cancer screening.
Authors: Y. Xu, Q. Xu, F. Liu, S. Ni, F. WU, X. Ye, B. Mougin, X. Meng, X. Du, S. Cai
Journal: Journal of Clinical Oncology (2011)

e14030 Background: Colorectal cancer is the second and third leading cause of cancer-related mortality for women and for men in the world. It is believed that more than 50% of these deaths may have been prevented through the use of screening tests. The compliance with current CRC screening recommendations remains poor. A simple blood-based test would represent an interesting alternative. We used DNA-microarrays and PAXgene to study the gene expression repertoires in peripheral blood, suitable for new biomarker discovery. Methods: 119 CRC patients and 101 non-CRC controls were enrolled in our study. RNA extracted from peripheral blood samples collected in PAXgene tubes, were analysed after NuGEN WT-Ovation RNA amplification, using Affymetrix GeneChip HG-U133 Plus 2.0 Array. Molecular signature discovery was performed based on 5-fold cross validation method, which means 4/5 of samples were used as internal train fold, prediction model was created with the top 100 genes scored by RFE-SVM, and then model performance was assessed with rest of samples. The process was run for 1000 iterations. Eventually, accuracy, sensitivity and specificity were used to measure the overall performance. Furthermore, we estimated the signature performance in an independent validation set, with 45 CRC patients and 47 non-CRC controls. Results: The overall performance based on cross validation process reached 95% (94.9, 95.3) accuracy, 95% (94.8, 95.2) sensitivity and 95% (95.0, 95.4) specificity. The signature performance in the independent test set reached 87.7% (77.9, 92.7) accuracy, 73.3% (57.8, 84.9) sensitivity and 100% (90.6, 100.0) specificity. The majorities of signature genes represent MHC class II receptoe activity, scavenger receptor activity, T cell proliferation and signal transduction information, implying the molecular changes occurring during disease progression. Conclusions: Our results demonstrated the feasibility of using gene expression profiling in peripheral blood to identify novel biomarkers. The CRC biomarker panel learned on the present dataset was considered as a promising transcriptomic biomarker for colorectal cancer screening.
Imaging techniques are useful in the surveillance after adjuvant treatment of colorectal cancer (CRC)
Authors: V. Arrazubi, M. Martinez Villacampa, M. Navarro, L. Pareja, M. Majem, J. Figueras, J. de Oca, A. Pisa, E. Nadal, J. R. Germa
Journal: Journal of Clinical Oncology (2005)

3653 Background: Surveillance in patients (pts) with CRC remains a controversial issue except detection of antigen carcinoembryonic (CEA) and colonoscopy. Better surgery and locoregional techniques along with more active regimens of chemotherapy (ChT) have improved the results of salvage treatments. Therefore imaging techniques may be useful in the detection of early relapses. We present our experience. Methods: From 1993 to 1999 all pts with stage II and III CRC treated with adjuvant treatment have been analysed. The follow-up schedule was clinical visit and CEA every 3 moths (m) 2 years (y), every 4 m the third y, every 6 m the fourth and fifth y and annually afterwards; chest X-ray annually and abdominal US every 6 m for 2 y and annually to complete 5 y. Abdominal CT scan was performed in rectal cancer (RC) annually for 2 y. Colonoscopy was done at first y and every 2 y. We calculate overall survival (OS) of the pts with relapses from date of relapse to death. Kaplan-Meier survival curves were compared with long rank test. Results: We analysed 611 pts, 311 colon (CC) (II 117, III 194) and 308 RC (II 124, III 84). Median age: 62 y (20;79); 352 M/267 F. ChT schedule: 5FU 245 pts(39,6%), 5FU-LV 124 pts (20%), 5FU-Lev 213 pts (34,4%); other 37 pts (6%). 314 pts received radiotherapy: 10 CC and 304 CR (pre/postoperative 82/222). Median follow-up is 66,9 m. Pts to assess: 583 (8 lost and 28 death without relapse). Relapses rate: 35,7%: locoregional (LR) 4,5% (26), sistemic (S) 26,4% (154) and both 4,8% (28). 83,6% of relapses were detected in the early 3 years. The first indicator of relapse was CEA in 57,2%, clinical visit in 14,4%, CT in 10%, abdominal US in 3,8%, chest X-ray in 4,8% and colonoscopy in 1%. In 8.7% pts data was not aviable. Potentially radical surgery was performed in 73 pts (35%): 12 LR(46,2%), 56 S(36,4%) and 5 LR+S (17.9%). 57.6% of the liver relapses as unique metastatic site were resected. All these relapses were detected by CEA in 50,1% and by imaging techniques in 30% as a first indicator. The median survival was 18 m: 62 m for pts with resected relapse and 12,4 m for pts with unresecable relapse (p<0.001). Conclusions: Surveillance imaging techniques are valuable components of postoperative follow-up in stage II and III CCR. No significant financial relationships to disclose.
An automated approach to the glycan analysis of cell surface proteins implicated in cancer metastasis
Authors: L. K. Pannell, E. R. Walp, J. C. Ruiz, L. A. Shevde-Samant, R. S. Samant, O. Fodstad
Journal: Journal of Clinical Oncology (2005)

9566 Background: Most cell surface proteins are glycosylated and several of the glycans present on the proteins have been documented to change in cancer. These include the selectins, integrins and E-cadherin. Changes in the glycans are implicated in metastasis, and are interesting selective targets for therapy. Despite recent advances in modern proteomics, glycosylation analysis is difficult, time-consuming, and often avoided. Even the analysis of a single site on a recombinant protein has required extensive work by a trained analyst. We have developed an automated approach which overcomes many of these hurdles. Methods: Protein targets which have significance in cancer are isolated with immunoprecipitation. They are digested with trypsin and the peptide mixture analyzed by LC-electrospray mass spectrometry. Only molecular weight information (MS-only) is obtained as distinct from most proteomic analyses where sequence information is the primary acquisition. The MS-only data is acquired with a high degree of mass accuracy on a HPLC-ESI-QTOF (Waters, Milford, MA). Using automated software package developed using standard glycoproteins (e.g. fetuin), the glycopeptides in the MS-only data are identified using precise mass gap analyses, and linked using a pattern recognition approach. The software analysis produces results which are often better than those determined by an expert in the field. Results: Cell membrane proteins are being isolated from a number of cancer and normal cell lines and their glycosylation patterns are being identified and characterized rapidly with this approach. Our results of the analyses on relevant cancer proteins will be compared to those determined by hand and referenced against those reported in the literature. Interestingly, the use of the automated analysis often produces more accurate results than could be obtained by hand. Conclusions: This new automated approach for glycan analyses and glycosylation characterization should be very useful in a clinical setting for the assessment of diagnostic and prognostic cancer markers. No significant financial relationships to disclose.
Knowledge and perceptions of palliative care among oncology outpatients.
Authors: Gillian McKie
Journal: Journal of Clinical Oncology (2015)

118 Background: Palliative care is emerging as an integral component of oncology care. There is growing evidence of its benefits but providers struggle with how to integrate specialist palliative services for the oncology population. The purpose of this study was to measure patients’ knowledge and perceptions, and their intention to seek palliative services. This study helps inform and guide oncology and palliative providers in their efforts to bridge the gap for oncology patients. Methods: The study used a cross-sectional design. A convenience sample of adult oncology patients using ambulatory cancer services at a community hospital was surveyed using the Knowledge of Care Options (KOCO) and Perceptions of Palliative Care Instrument (PPCI). Clinical information was abstracted from their health records retrospectively. Descriptive statistics were used to describe all variables. The association between knowledge, perceptions, and intention was analyzed using Pearson’s r correlation and multivariate regression analysis. Results: The majority of the 139 participants enrolled were female (61.9%), white (76.7%), and had good functional status with ECOG of 0 or 1 (87.1%). Mean age was 63.4 years. The mean KOCO score was 84.4% although several items scored less than 70%. Overall intention to seek palliative care was low at 2.53 on a seven point scale; a majority of patients indicated that they were unlikely to seek palliative care. There was a positive correlation between overall perception and intention to seek palliative care in the next three months (r = 0.212, p = 0.02).In addition, patients with higher scores on perceived needs for palliative care were more likely to report an intention to seek palliative care (r = 0.308, p = 0.001). Conclusions: There remains a knowledge deficit about palliative care in the oncology population. Participants did not experience negative emotional or cognitive reactions in response to information about palliative care. Perceived needs were associated with intention to seek palliative care services. Routine screening for needs and effective educational strategies are needed to better integrate palliative and oncology care.
PUMILIO/FOXP1 signaling drives expansion of hematopoietic stem/progenitor and leukemia cells
Authors: Cécile Naudin, Aurore Hattabi, Fabio Michelet, Ayda Miri-Nezhad, Aissa Benyoucef, Françoise Pflumio, François Guillonneau, Serge Fichelson, Isabelle Vigon, Isabelle Dusanter-Fourt, Evelyne Lauret
Journal: Blood (2017)
Sensitivity of second-generation blood-based methylated Septin9 assay for early-stage colorectal cancer.
Authors: Gunter Weiss, Anne Fassbender, Thomas Koenig, Reimo Tetzner
Journal: Journal of Clinical Oncology (2012)

419 Background: Early detection of colorectal cancer (CRC) has been shown to decrease mortality, although compliance to CRC screening is low. Availability of a blood-based test is expected to improve CRC screening compliance. Specific detection of CRC using the Septin9 biomarker ( m SEPT9) in a large prospective trial of an average-risk CRC screening population exhibited 67% sensitivity for CRC with 88% specificity. Laboratory-developed tests detecting m SEPT9 in plasma are now available in North America and a 2 nd generation molecular diagnostic blood test for m SEPT9 is available as a CE-marked kit in Europe. The current research evaluated the clinical performance of the 2 nd generation m SEPT9 assay. Methods: Bisulfite-converted DNA (bisDNA) was prepared from 3.5 mL human plasma using the 2 nd generation plasma DNA preparation kit. Resulting bisDNA was analyzed in triplicate on the ABI7500 Fast Dx (Life Technologies, Inc.) using proprietary HeavyMethyl real-time PCR technology for m SEPT9 and the 2 nd generation real-time PCR kit. In a case – control design, plasma from 98 CRC patients (n = 87 stages I - III) and 99 age-matched, colonoscopy-verified normal individuals were processed with the m SEPT9 assay. In addition, plasma from 150 prospectively enrolled average risk individuals scheduled for screening colonoscopy was tested. m SEPT9 was qualitatively analyzed such that any detection of m SEPT9 in a PCR was called “positive”. Results: The revised m SEPT9 assay exhibited 95% sensitivity (95% CI: 89-98%) for CRC. Sensitivity for stage I was 89% (95% CI: 72-96%, n = 27) and sensitivity for stage II was 93% (95% CI: 78-98%, n = 29). The control group was positive at a rate of 16% (95% CI: 10-25%). Specificity of the m SEPT9 assay in the screening cohort was 85% (95% CI: 78-89%). Conclusions: The 2 nd generation m SEPT9 assay demonstrated improved sensitivity for CRC without significant impact on specificity. The enhanced design and robustness of the assay will further facilitate its standardized use in routine laboratory settings. Finally, the increased sensitivity of the revised m SEPT9 assay improves the detection of early stage disease and demonstrates the feasibility of a blood-based CRC screening technology.
Selectively Inducing Cancer Cell Death by Intracellular Enzyme‐Instructed Self‐Assembly (EISA) of Dipeptide Derivatives
Authors: Jie Li, Junfeng Shi, Jamie E. Medina, Jie Zhou, Xuewen Du, Huaimin Wang, Cuihong Yang, Jianfeng Liu, Zhimou Yang, Daniela M. Dinulescu, Bing Xu
Journal: Advanced Healthcare Materials (2017)

Tight ligand‐receptor binding, paradoxically, is a major root of drug resistance in cancer chemotherapy. To address this problem, instead of using conventional inhibitors or ligands, this paper focuses on the development of a novel process—enzyme‐instructed self‐assembly (EISA)—to kill cancer cells selectively. Here it is demonstrated that EISA as an intracellular process to generate nanofibrils of short peptides for selectively inhibiting cancer cell proliferation, including drug resistant ones. As the process that turns the non‐self‐assembling precursors into the self‐assembling peptides upon the catalysis of carboxylesterases (CES), EISA occurs intracellularly to selectively inhibit a range of cancer cells that exhibit relatively high CES activities. More importantly, EISA inhibits drug resistant cancer cells (e.g., triple negative breast cancer cells (HCC1937) and platinum‐resistant ovarian cells (SKOV3, A2780cis)). With the IC 50 values of 28–80 and 25–44 µg mL −1 of l ‐ and d ‐dipeptide precursors against cancer cells, respectively, EISA is innocuous to normal cells. Moreover, using coculture of cancer and normal cells, the selectivity of EISA is validated against cancer cells. Besides revealing that intracellular EISA cause apoptosis or necroptosis to kill the cancer cells, this work illustrates a new approach to amplify the enzymatic difference between cancer and normal cells and to expand the pool of drug candidates for potentially overcoming drug resistance in cancer therapy.
Health care quality experiences among cancer survivors in the United States, 2011.
Authors: Janice Bell, Robin L. Whitney, Sarah Reed, Andra Davis, Katherine Kim, David Copenhaver, Richard J. Bold, Jill G. Joseph
Journal: Journal of Clinical Oncology (2014)

246 Background: Recent national reports highlight gaps in the quality of health care received by the growing population of cancer survivors in the United States. A deeper understanding of the health care experiences of cancer survivors and related disparities could inform interventions designed to address these gaps. Methods: Data from the 2011 Medical Expenditures Panel Survey Household Component and Experiences with Cancer Survivorship Supplement (n=1,592) were used to compare health care experiences of survivors those those of individuals in active treatment. Logistic regression models of three outcomes (receipt of necessary care; detailed discussions with providers about late or long-term side effects of cancer treatment; and detailed discussions with providers about lifestyle or health recommendations e.g., diet, exercise, quitting smoking) were controlled for potential confounding variables including age, sex, health insurance status, education, race/ethnicity, and marital status. Survey weights were applied to account for the complex sampling design and estimates are generalizable to the US civilian, non-institutionalized population. Results: Most respondents (96%), whether or not they were in active treatment, reported they had received all medical care, tests, or treatments that they or their providers believed were necessary. Fewer survivors, compared to respondents in active treatment, reported their providers had discussed late or long-term side effects (37% versus 61%; p&lt;0.01) or lifestyle recommendations with them in detail (57% versus 72%). These associations persisted in the multivariable models of side effect discussions (OR=0.38; 95% CI: 0.26, 0.55) and lifestyle recommendations (OR=; 95% CI: 0.35, 0.68) regardless of the length of time since treatment had finished. Subgroups with lower odds of all three outcomes included those with public or no insurance and those with lower levels of education. Conclusions: Care received after treatment for cancer may not fully address the unique needs of cancer survivors and, in particular, those with public or no insurance and with low levels of education regardless of treatment status. Targeted interventions with a focus on these subgroups may be required.
Complication rates in patients with uncontrolled diabetes undergoing radical cystectomy: A population-based study.
Authors: Izak Faiena, Viktor Y. Dombrovskiy, Raymond C. Sultan, Yanina Barbalat, Amirali H. Salmasi, Eric A. Singer, Robert E. Weiss
Journal: Journal of Clinical Oncology (2015)

355 Background: Radical cystectomy is known to be associated with a relatively high incidence of postoperative morbidity and mortality. We evaluated the complication rates of a population-based cohort of patients with uncontrolled diabetes who underwent radical cystectomy. Methods: The data for this analysis was captured from the NIS (Nationwide Inpatient Sample) 2002-2009. Among patients who underwent radical cystectomy (ICD-9 diagnosis code 188.x and 57.71), we selected those with uncontrolled diabetes, which is defined by the billing physician (ICD-9 diagnosis code 250.02) and compared to patients without diabetes. We also identified postoperative complications. Patient socio-demographic characteristics, principal and secondary diagnoses, principal and secondary procedures, comorbid diseases, disposition of patient at discharge, hospital length of stay, and hospital cost for our analysis. A chi-square test was employed for categorical variables and Student’s t-test for continuous variables. A multivariable logistic regression analysis was also employed with computing OR and 95% CI. P&lt;0.05 was considered statistically significant. Results: There were significant differences in the postoperative outcomes between groups. In the univariable analysis, patients with uncontrolled diabetes were more likely to have complications (OR=3.21; 95%CI= 2.59-4.00) including infectious complications (OR=2.46; 95%CI= 1.98-3.06) and were more likely to die during the index hospitalization (OR=3.27; 95%CI= 1.41-7.61). Hospital resource utilization was also significantly greater in patients with uncontrolled diabetes. Mean length of stay in this group was 17.3 days compared to 11.4 days in non-diabetic group (P=0.0007); total hospital cost was, respectively, $47,960 and $32,422 (P=0.0009). Conclusions: This study demonstrates a significant association between uncontrolled diabetes and in-hospital post-cystectomy complications, mortality, and hospital resource utilization. This study highlights the recognition of uncontrolled diabetes as a potential modifiable risk factor for patients undergoing cystectomy.
The mechanism of endostar on ascites formation in vivo and in vitro.
Authors: S. Qin, X. Yin, Y. Chen, W. Hongmei
Journal: Journal of Clinical Oncology (2011)

e21013 Background: Angiogenesis and vessel hyperpermeability are the two important factors leading to the formation of ascites. Many studies have demonstrated that Endostar strongly inhibits the growth of a variety of murine and xenotransplanted human tumors by suppressing the neovascularization. The study was designed to explore the mechanism of action correlated with tumor ascites in vivo and in vitro. Methods: In vivo, the mice models of tumor ascites with S180 and H22 cell lines were established. Model animals were randomly distributed into 4 groups with 12 mice respectively. 3 groups received different doses of endostar treatment.The control group received 0.9% normal saline. Four mice in each group were undertaken peritoneal capillar permeability experiments. The mice were slowly injected with 0.25 ml of 5 % Evan blue dye from vena caudalis. After 2 h, the mice were killed to collect ascites. The optical density of Evan blue was measured at 540 nm wavelength to indirectly reflect the concentration of Evan blue dye. In vitro, MTT assay was performed to evaluate the proliferation of S180 and H22 cells in the absence or presence of endostar. Tumor cells (1×104cells/well) were incubated with various concentrations of endostar. Invasiveness of Endostar on tumor cells was determinated by Transwell invasion chamber model. Results: In vivo. Results showed that Endostar (dose at 8,16mg/kg) could markedly suppress ascites production and peritoneum permeability, and down-regulated the levels of VEGF, MMP-2 and CD44v6 in blood serum and ascites fluid (P<0.05, respectively). Endostar showed mild apoptosis and cell cycle on S180 and H22 cells (P>0.05). In vitro. Results from incubation of S180 cells and H22 cells with various concentrations of endostar suggested significant inhibition of VEGF, MMP-2 and CD44v6 by ELISA (P<0.05, respectively),and down-regulated the expressions of VEGFmRNA and OPNmRNA by Real-time PCR, and reduced the expressions of OPN, αVβ3 integrin and HIF-1α by Western blot analysis. Conclusions: Those results revealed for the first time that Endostar could profoundly suppress ascites formation through the expressions of VEGF, MMP2, CD44v6, OPN and αVβ3 integrin, rather than induced cells apoptosis and proliferation.