tbuckley/cabot-search huggingface dataset:
Abstract 107: Unsupervised analysis of cancer-cell intrinsic transcriptional traits defines a new classification system for colorectal cancer with improved predictive and prognostic value
Authors: Andrea Bertotti, Claudio Isella, Sara E. Bellomo, Francesco Brundu, Francesco Galimi, Elisa Ficarra, Livio Trusolino, Enzo Medico
Journal: Cancer Research (2016)

Abstract Recent work built on published transcriptional subtypes of colorectal cancer (CRC) has shown that tumor stromal content heavily impacts CRC classification, with clinical and biological implications. Lineage-dependent transcriptional components of stromal origin could therefore dominate over more subtle, yet relevant, gene expression traits inherent to cancer cells. Based on the notion that in patient-derived xenografts (PDXs) stromal cells of the human tumor are substituted by their murine counterparts, we assessed cancer-cell intrinsic transcriptional features by human-specific expression profiling on 515 PDXs from 244 CRC patients. We identified five CRC intrinsic subtypes (CRIS) endowed with molecular, functional and phenotypic peculiarities, many of which were not previously evidenced: CRIS-A was a MIN-like, KRAS-mutated, and secretory subtype with sustained glycolytic metabolism and inflammatory traits; CRIS-B grouped a subset of poorly differentiated tumors with active TGFβ signaling and EMT features; CRIS-C clustered KRAS wild-type CIN tumors exhibiting elevated EGFR pathway activity and MYC copy number gains; CRIS-D tumors were characterized by a typical stem phenotype with high WNT signaling, associated with strong enrichment in IGF2 amplification/overexpression and FGFR autocrine stimulation; CRIS-E again displayed WNT-related features, but associated with a Paneth-like phenotype and a TP53-mutated genotype. CRIS subtypes successfully categorized independent sets of primary and metastatic CRC tumors, with limited overlap on existing transcriptional classes and unprecedented predictive and prognostic performances. Integration of stroma-centered transcriptional profiles with cancer-cell intrinsic classification by CRIS further enhanced prognostic significance. Citation Format: Andrea Bertotti, Claudio Isella, Sara E. Bellomo, Francesco Brundu, Francesco Galimi, Elisa Ficarra, Livio Trusolino, Enzo Medico. Unsupervised analysis of cancer-cell intrinsic transcriptional traits defines a new classification system for colorectal cancer with improved predictive and prognostic value. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 107.
Gemcitabine in combination with cisplatin (GP) versus gemcitabine (G) alone in the treatment of locally advanced or metastatic pancreatic cancer: Final results of a multicenter randomized phase II study
Authors: F. Viret, M. Ychou, D. Lepille, L. Mineur, F. Navarro, D. Topart, M. Fonck, J. Goineau, A. Madroszyk-Flandin, N. Chouaki
Journal: Journal of Clinical Oncology (2004)

4118 Background: The survival of patients (pts) with locally advanced or metastatic pancreatic cancer could be improved by the addition of P to standard chemotherapy with G. Methods: The primary objective was to compare time to treatment failure (TTF) of pts treated with GP versus G. Secondary objectives were to compare toxicity, overall survival time (OST), quality-adjusted time without symptoms or toxicity (Q-TWiST analysis), and quality of life (EORTC QLQ-C30 questionnaire) between arms and to assess objective response rate (ORR) and duration of response in the two arms. Chemonaive pts age 18–75 yrs with histologically proven stage III or IV pancreatic cancer were randomized to receive G 1000 mg/m2/wk × 3 plus P 75 mg/m2 on day 15 every 4 wks (GP arm) or G 1000 mg/m2/wk × 7 followed by 1 week of rest for cycle 1, and then G at the same dose × 3 every 4 wks (G arm). Results: From July 2000 to August 2002, 83 pts (42 GP, 41 G) received a median of 4 and 3 cycles for GP and G, respectively. Baseline characteristics (GP/G) were stage III disease in 8/9 and stage IV in 34/32 pts; median age of 61.5 yrs/63 yrs; and WHO PS 0–1 in 32/34 and PS 2 in 10/7 pts. The median TTF was 65 days (95% CI, 52–145) for GP and 76 days (95% CI, 52–111) for G (p=.67). Respective median OST was 241 days (95% CI, 130–295) and 201 days (95% CI, 133–326) (p=.73). Additionally, 7% of GP pts had PR and 48% had SD, while 5% of G pts had PR and 46% had SD. Q-TWiST results did not differ significantly between the two arms. Median dose intensities were 92% G and 69% P (GP) and 94% (G). The main CTC grade 3/4 toxicities (% pts) for GP/G included neutropenia (56/40), anemia (37/28), nausea (15/5), vomiting (7/3), anorexia (2/0); in particular, the incidence of grade 3/4 thrombocytopenia (34/13; p=.03) and asthenia (5/10; p=.04) differed significantly between arms. Conclusions: The addition of P to G does not appear to improve the prognosis of pts with locally advanced or metastatic pancreatic cancer. Other gemcitabine-based combinations should be evaluated. No significant financial relationships to disclose.
P0512 : Liver stiffness measurments using fibroscan after three months of IFN-based antiviral therapy is unlikely to predict viral response in cirrhotic patients
Authors: N. Gamal, L. Brodosi, A. Scuteri, G. Simonetti, C. Cursaro, M. Mastroroberto, M. Bernardi, P. Andreone
Journal: Journal of Hepatology (2015)
Abstract 2861: Validation of PERK as an oncology target: A role for the unfolded protein response in cancer
Authors: Ken Dellamaggiore, Petia Mitchell, Ji-Rong Sun, Jeffrey Jones, Tony Muchamuel, David Hollenback, Seifu Tadesse, Shon Booker, Fang-Tsao Hong, Adrian Smith, Mark Rose, Pedro Beltran, James R. Lipford
Journal: Cancer Research (2016)

Abstract The Unfolded Protein Response (UPR) is a cellular stress response to stressors that induce accumulation of unfolded proteins in the endoplasmic reticulum (aka ER stress). The UPR protects cells from ER stress by increasing the capacity of the ER and attenuating bulk translation. Intense or unresolved ER stress induces apoptosis through pro-apoptotic factors like CHoP. The UPR is activated in tumors, especially those of hematological origin. PERK, a UPR sensor-kinase, is highly active in these settings and might be an attractive target in oncology. We have generated multiple potent, selective PERK inhibitor scaffolds. Low doses of PERK inhibitor (&amp;lt; pPERK IC50) activate the downstream pathway, whereas higher doses return the pathway to baseline, resulting in a bell-shaped activity curve for all pathway readouts. The activation phase results in robust, selective killing of tumor cells in vitro and in vivo, likely through sustained translation inhibition and CHoP induction. However, application in the clinic will be challenging due to irreversible toxicity to pancreatic islets at constant, high doses and difficulty managing human dosing through a bell curve. Emerging data might provide a solution to these challenges. PERK IP-kinase assays demonstrate that compound binding at any dose activates PERK and this activity is retained after compound removal. Exposure modeling in vitro demonstrates that transient dosing followed by compound removal results in a conventional sigmoidal dose-response curve for viability. Intermittent dosing in vivo results in CHoP induction and tumor growth inhibition even at very high doses of PERK, consistent with PERK activation following compound clearance. These findings suggest that optimized scheduling might drive robust tumor growth inhibition with reduced risk of toxicity and facilitate a standard clinical dose escalation. Citation Format: Ken Dellamaggiore, Petia Mitchell, Ji-Rong Sun, Jeffrey Jones, Tony Muchamuel, David Hollenback, Seifu Tadesse, Shon Booker, Fang-Tsao Hong, Adrian Smith, Mark Rose, Pedro Beltran, James R. Lipford. Validation of PERK as an oncology target: A role for the unfolded protein response in cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2861.
Lifetime smoking history and four most common types of cancer and other causes of mortality in a large cohort study with 43 years of follow-up.
Authors: Niloofar Taghizadeh, Judith M. Vonk, H. Marike Boezen
Journal: Journal of Clinical Oncology (2015)

e12630 Background: In general, smoking increases the risk of mortality. However, it is unclear which specific cause of death carries the highest risk. Moreover, the impact of changes in smoking habits throughout life on mortality is less studied. Methods: We studied the impact of baseline and lifetime smoking habits, duration of smoking and duration of smoking cessation on the risk of all-cause mortality, mortality of cardiovascular diseases (CVD), and mortality of any cancer and lung, colorectal, prostate, and breast cancer, in a large cohort study (Vlagtwedde-Vlaardingen 1965-1990, with follow-up on mortality until 2009, n = 8,645). We used Cox regression models adjusted for age, BMI, sex, and place of residence. To determine which cause of death carried the highest risk we performed competing-risk analyses on mortality due to cancer, CVD and other causes. Results: Current light, moderate, and heavy cigarette smokers, and lifetime persistent smokers had a higher risk of all-cause, CVD, any cancer, and lung cancer mortality compared to never smokers. A longer duration of smoking associated with a higher risk of any and lung cancer [HR (95% CI) = 1.03 (1.00-1.06) and 1.10 (1.03-1.17) respectively], but not with other mortality causes. A longer duration of smoking cessation associated with a lower risk of all-cause and any cancer mortality. The competing risk analyses showed that ex- and current smokers had a higher risk of both cancer and CVD mortality compared to all other mortality causes. In addition, heavy smokers had a higher risk for cancer mortality compared to CVD. Conclusions: Our findings emphasize on the importance of smoking-related competing risks when studying the smoking-related cancer mortality in a general-population and that smoking cessation effectively reduces the risk of all-cause and any cancer mortality.
After 12 years, where next for QOF?
Authors: Nicholas Steel, Paul Shekelle
Journal: BMJ (2016)

With bold innovation, QOF has the potential to lead the charge on patient centred care 

The recent EU referendum result reminds us that behaviour is not simply determined by economic self interest, yet the notion of paying physicians to perform remains remarkably popular. Medicare payments in the US are increasingly linked to the quality of services, and pay for the 32 000 UK general medical practitioners working for the National Health Service has been linked to quality of care through the Quality and Outcomes Framework (QOF) since 2004.1 2

Back then, quality indicators for general practice were new, and electronic medical records had become widespread in British general practice.3 The UK Department of Health wanted to improve population coverage of healthcare processes that had evidence of improved health outcomes and invested £8bn (€9.5bn; $10.5bn) over the first three years of QOF to reward performance in four areas: clinical, organisational, patient experience, and additional services. There were 80 clinical indicators in 2004 and 77 in 2016, covering cardiovascular disease, diabetes, …
<i>KRAS</i>in Non–Small-Cell Lung Cancer
Authors: Stéphane Renaud, Michèle Beau-Faller, Gilbert Massard
Journal: JAMA Oncology (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Stage specific health utility index scores of Canadian cancer patients.
Authors: Hiten Naik, Doris Howell, Jie Su, Xin Qiu, Catherine Brown, Ashlee Vennettilli, Margaret Irwin, Vivien Pat, Hannah Solomon, Tian Wang, Henrique Hon, Lawson Eng, Mary Mahler, Henry Thai, Valerie Ho, Wei Xu, Soo Jin Seung, Nicole Mittmann, Geoffrey Liu
Journal: Journal of Clinical Oncology (2015)

6614 Background: In order to improve the precision of health economics analyses in oncology, reference datasets of health utility index (HUI) scores are needed from cancer patients. These data are particularly sparse among Canadian patients. Using EQ5D we generated stage-specific HUI scores for lung, breast, colorectal, prostate, head/ neck and ovarian cancer, and all-stage reference values for 21 additional cancer sites. Methods: 1,760 ambulatory cancer patients at the Princess Margaret completed the EQ5D instrument. HUI scores were calculated using Canadian valuations. Clinical information was abstracted from patient charts and data was analyzed using descriptive statistics and multiple regression. Results: Among all patients, the mean±SEM HUI score was 0.81±0.004 (Canadian algorithm). The cancer sites with the lowest mean HUI scores were acute lymphoblastic leukemia (0.70±0.03) and pancreatic (0.76±0.03); testicular (0.89±0.02) and chronic lymphocytic leukemia (0.90±0.05) had the highest scores. Scores varied by stage among lung, breast, colorectal, prostate, head and neck and ovarian cancer patients (see Table). After adjusting for age and cancer site, HUI scores were significantly higher amongst patients with a university/ college education (p = 0.002), those married or living with a partner (p < 0.001), employed (p < 0.001), and those with local/regional vs. distant metastatic disease (p = 0.001). Conclusions: This work represents the first reference set of stage specific HUI scores for several cancers derived using Canadian valuations. Mean HUI scores varied by basic socio-demographic and clinical parameters, including stage. Future research will incorporate these data into the economic analyses required for policy and clinical decision-making. Stage Lung Breast Colorectal Prostate Head/Neck Ovarian N HUI ±SEM N HUI± SEM N HUI ±SEM N HUI ±SEM N HUI ±SEM N HUI ±SEM 0 --- --- 19 0.91±0.02 --- --- --- --- 5 0.90±0.06 --- --- 1 43 0.81± 0.03 97 0.82±0.02 4 0.80±0.07 26 0.92±0.02 36 0.86±0.02 13 0.82±0.04 2 16 0.77± 0.03 102 0.79±0.02 26 0.87±0.02 60 0.92±0.01 20 0.83±0.04 10 0.81±0.06 3 32 0.76±0.03 34 0.74±0.04 48 0.83±0.02 19 0.83±0.05 19 0.78±0.05 49 0.77±0.02 4 37 0.76±0.03 16 0.81±0.04 34 0.81±0.02 10 0.78±0.04 61 0.81±0.01 6 0.77±0.04
Genetic pleiotropy in complex traits and diseases: implications for genomic medicine
Authors: Jacob Gratten, Peter M. Visscher
Journal: Genome Medicine (2016)

Several recent papers have used summary results from genome-wide association studies to characterize genetic overlap between human complex traits and common diseases.The emerging evidence is that individual DNA variants frequently influence multiple phenotypes, often in unexpected ways.This has important implications for genomic medicine and for the application of genome editing.
Abstract 243: Investigating microtubule growth dynamics in patient-derived metastatic prostate cancer cells
Authors: Alexandre Matov, Johan de Rooij, Jay Gatlin, Julia Rohrberg, Nikta Ahmad, Rahul Aggarwal, Jeff Simko, Andrei Goga, Charles Ryan, Torsten Wittmann
Journal: Cancer Research (2016)

Abstract Advanced prostate cancer (PC) is treated primarily by means of chemotherapy with one of the clinically approved microtubule (MT)-targeting agents (MTAs): paclitaxel, docetaxel and cabazitaxel. The mechanism of action of the MTAs on the cellular level is to bind to MTs and inhibit MT-dependent intracellular pathways, ultimately leading to cell death. In PC, MTAs are the only chemotherapy class shown to improve survival, however, there is high variability of response to MTA chemotherapy among patients as well as emergence of resistance to drug action which hampers the clinical efficacy. Clinicians need additional information to match individual patient tumors to the most effective drugs or refrain from treating patients that will not respond. However, the precise mechanism of action or resistance development to MTAs is not understood, which represents a critical gap in our knowledge to select the best treatment. Our hypothesis is that there are inherent differences in tumor MT dynamics among individual patients which dictates their response to treatment with specific MTAs. To this end, we envision that a systematic characterization of PC MT dynamics and their response to MTAs will allow chemotherapy customization and prolong survival. Specifically, our approach consists of the analysis of metastatic castrate resistant PC (mCRPC) organoids (Gao D. et al, 2014) derived from bone (acetabulum, vertebrae), soft tissue (salvage prostatectomy, lymph nodes), pleural effusion and circulating tumor cells biopsy samples obtained from metastatic patients who have received hormonal therapy and the MTA docetaxel or hormonal therapy alone or no treatment. We apply a quantitative single-cell image analysis algorithm (ClusterTrack) to measure a panel of twelve distinct MT dynamics parameters (a MT dynamics signature). Preliminary analysis suggests differences between different mCRPC organoids. MT tracking results indicate a correlation of decreased MT growth rate with increased Op18/stathmin expression. In this context, we hypothesize that differential expression of MT regulating genes affects specific parameters of MT dynamics, thus determining the sensitivity to MTA treatment. Citation Format: Alexandre Matov, Johan de Rooij, Jay Gatlin, Julia Rohrberg, Nikta Ahmad, Rahul Aggarwal, Jeff Simko, Andrei Goga, Charles Ryan, Torsten Wittmann. Investigating microtubule growth dynamics in patient-derived metastatic prostate cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 243.
Abstract CT124: A phase II study of bevacizumab and irinotecan as second-line therapy for patients with metastatic colorectal cancer previously treated with fluoropyrimidine, oxaliplatin, and bevacizumab
Authors: Go Nakajima, Hidekazu Kuramochi, Masayuki Ando, Michio Itabashi, Kazuyuki Kawakami, Mie Hamano, Eiichi Hirai, Takayuki Iino, Hajime Yokomizo, Ryuji Okuyama, Tatsuo Araida, Kazuhiko Yoshimatsu, Shingo Kameoka, Kazuhiko Hayashi
Journal: Cancer Research (2016)

Abstract Background: FOLFIRI plus bevacizumab (BV) is widely used as second-line chemotherapy for patients with metastatic colorectal cancer (mCRC) previously treated with FOLFOX/XELOX plus bevacizumab. However, there is insufficient data characterizing the effectiveness of administration of fluoropyrimidine beyond first disease progression. FOLFIRI requires using a CV catheter. Oral fluoropyrimidine may cause severe diarrhea when administered with irinotecan (CPT-11). CPT-11+BV may overcome those problems. Methods: Patients with mCRC previously treated with at least four courses of fluoropyrimidine, oxaliplatin, and bevacizumab were designated to receive 150 mg/m2 of CPT-11 and 10 mg/kg of BV, every 2 weeks as second-line therapy. The primary endpoint was progression-free survival (PFS), and secondary endpoints included response rate (RR), overall survival (OS), and adverse events. Results: Thirty patients from six institutes were enrolled from March 2011 to January 2014. Twenty-five (83.3%) patients were refractory to first-line therapy and eight patients (16.6%) were unable to tolerate first-line therapy. The median PFS was 5.7 months (95% CI; 4.2-7.3 months) and the RR was 6.7% (range, 0.8-22.1%. Grades 3-4 adverse events included leucopenia (36.7%), neutropenia (50%), thrombocytopenia (26.7%), anemia (30%), diarrhea (3.3%), anorexia (6.7%), and hypertension (3.3%). Relative dose intensities were 94.5% and 96.3% for CPT-11 and BV, respectively. Median OS was 11.8 months (6.3 months-not reached). Conclusions: Administration of CPT-11 plus BV to patients with mCRC achieved comparable efficacy with relatively lower toxicities compared with the results of previous studies using FOLFIRI plus BV as second-line therapy. The dose intensity of CPT-11 was judged satisfactory. Clinical trial information: UMIN000005228 Citation Format: Go Nakajima, Hidekazu Kuramochi, Masayuki Ando, Michio Itabashi, Kazuyuki Kawakami, Mie Hamano, Eiichi Hirai, Takayuki Iino, Hajime Yokomizo, Ryuji Okuyama, Tatsuo Araida, Kazuhiko Yoshimatsu, Shingo Kameoka, Kazuhiko Hayashi. A phase II study of bevacizumab and irinotecan as second-line therapy for patients with metastatic colorectal cancer previously treated with fluoropyrimidine, oxaliplatin, and bevacizumab. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT124.
Impact of Mutation Status of ASXL1, EZH2, SRSF2, IDH1/2 on Clinical Phenotype and Prognosis in Patients with Post-Polycythemia and Post-Essential Thrombocythemia Myelofibrosis: An AGIMM Study
Authors: Giada Rotunno, Annalisa Pacilli, Giada Brogi, Valentina Artusi, Elisa Rumi, Federica Delaini, Carmela Mannarelli, Flavia Biamonte, Rajmonda Fjerza, Lisa Pieri, Daniela Pietra, Clara Belotti, Enrico Tagliafico, Rossella Manfredini, Isabella Bernardis, Alberto Bosi, Alessandro Rambaldi, Tiziano Barbui, Alessandro Maria Vannucchi, Paola Guglielmelli
Journal: Blood (2014)
Pyrimidine 5′ Nucleotidase-1 (P5N-1) Deficiency Associated with 4 Novel Mutations in 5 New Turkish Families: Genotype-Phenotype Analysis.
Authors: Gunay Balta, Aytemiz Gurgey, Fatma Gumruk, Yahya Buyukasik, Meral Beksac, Cigdem Altay
Journal: Blood (2006)