tbuckley/cabot-search huggingface dataset:
Erratum: Corrigendum: Stromal contribution to the colorectal cancer transcriptome
Authors: Claudio Isella, Andrea Terrasi, Sara Erika Bellomo, Consalvo Petti, Giovanni Galatola, Andrea Muratore, Alfredo Mellano, Rebecca Senetta, Adele Cassenti, Cristina Sonetto, Giorgio Inghirami, Livio Trusolino, Zsolt Fekete, Mark De Ridder, Paola Cassoni, Guy Storme, Andrea Bertotti, Enzo Medico
Journal: Nature Genetics (2016)
A phase II study of HSP90 inhibitor AUY922 and erlotinib (E) for patients (pts) with EGFR-mutant lung cancer and acquired resistance (AR) to EGFR tyrosine kinase inhibitors (EGFR TKIs).
Authors: Melissa Lynne Johnson, Eric M Hart, Alfred Rademaker, Bing Bing Weitner, Alexandra Urman, Hala D Simm, Leanne M Fountas, Rebekah Worden, Jyoti D. Patel, Vincent A. Miller, Gregory J. Riely
Journal: Journal of Clinical Oncology (2013)

8036 Background: AUY922 is a synthetic HSP90 inhibitor that degrades client onco-proteins including EGFR. Preclinical studies demonstrate HSP90 inhibitors are effective agents against models of AR in EGFR-mutant lung cancer cell lines and xenografts harboring the “gatekeeper” mutation EGFR T790M. Pts with EGFR mutations who develop AR often continue E with 2nd-line therapies to avoid “disease flare” associated with discontinuing TKI. This phase II study combines AUY922 and E for the treatment of pts with EGFR-mutant lung cancer and RECIST-progression on 1st-line EGFR TKIs. Methods: Eligible pts had EGFR mutations and developed AR (Jackman, JCO 2010) after treatment with EGFR TKIs. Pts underwent tumor biopsies after developing AR and prior to study entry. Pts received AUY922 70 mg/m 2 IV weekly and E 150 mg oral daily in 28-day cycles. Response assessment occurred at 4 weeks (wks), 8 wks, and every 8 wks thereafter. The primary objective was overall response rate (ORR, CR+PR) at 8 wks. A Simon mini-max design determined sample size (stage I: 16 pts (≥2 responses needed to proceed to stage II), stage II: 9 pts; α=10%, β=10%, p0=10%, p1=30%). Tumor tissue from re-biopsy at study entry was analyzed for EGFR T790M. Results: Sixteen pts have been treated (10 women, median age 58 [range 47-76]). The median time on EGFR-TKI prior to the development of AR was 12 mo (range 2-42 mo). Seven pts had EGFR T790M confirmed by tumor re-biopsy. ORR was 2/16 (13%, 95% CI 2-37%). Both pts with PR had EGFR T790M. Four other pts had stable disease for at least 8 wks, two remain on study after more than 12 wks. Adverse events reported in ≥20% of pts were diarrhea, fatigue, myalgias, nausea, and transient flashing lights or night blindness. One pt each experienced grade 3 diarrhea and cardiac abnormalities. Conclusions: AUY922 and E is a well-tolerated regimen for pts with EGFR-mutant lung cancer and AR to EGFR TKIs. Two pts remain on study and 9 additional pts will be accrued in stage II; final response rate and survival outcomes will be reported. Supported by Novartis, Inc. Clinical trial information: NCT01259089.
Medical school “banter” denigrating GPs and psychiatrists must stop, say college heads
Authors: Gareth Iacobucci
Journal: BMJ (2016)

Two of the UK’s most senior doctors have called for an end to the damaging “banter” in medical schools, which they claim is dissuading students from applying to general practice and psychiatry.

Maureen Baker, chair of the Royal College of general practitioners, and Simon Wessely, president of the Royal College of Psychiatrists, said that “the systematic denigration” of their specialties was putting patient safety at risk by contributing to a shortfall of GPs across the country and was stifling efforts to achieve parity of esteem between physical and mental health.

In a joint editorial in the British Journal of General Practice ,1 …
Correlation of serum ESR1 methylation levels with RE status in tumor and molecular subtypes of breast cancer.
Authors: J. Martínez-Galán, B. Torres-Torres, J. Valdivia, R. Del Moral, M. Núñez, R. Luque, J. M. Jurado, J. Peñalver, M. Ruiz De Almodovar, J. Delgado
Journal: Journal of Clinical Oncology (2010)

e13648 Background: To determine whether estrogen receptor (ER) (+) and ER (-) status relates to epigenetic changes in breast cancer-related genes and to correlate with molecular breast cancer subtypes. Methods: From January 2002 to June 2005, we quantified methylation levels ERS1 gene in serum of 92 pts breast cancer. A PCR quantitative technique was used to analyze levels of methylation gene. We also examined and correlationed the expression of ESR1 AND HER2+ in tumors by immunohistochemistry with molecular phenotype. Results: Median age was 58 years (32-88); 69% were postmenopausal women. Nodal involvement (N0;63%,N1;30%,N2;7%), tumor size (T1;58%, T2;35%, T3;4%, T4;4%) and grade (G1;20%, G2;37%, G3;30%). Of the cases, 37pts (40%) were Luminal A (LA), 32pts (33%) Luminal B (LB), 14pts (15%) triple-negative (TN), and 9pts (10%) HER2+. The methylated ESR1 in serum was significantly associated with ER(-) in breast tumors >80% (p=0.0179). Methylation ESR1 was preferably associated with TN (80%) and HER2+ (60%) subtype. Nevertheless unmethylation ESR1 was found more frequently in LA (71%) and LB (59%) phenotype. With a median follow up of 5 years, we found worse overall survival (OS) with more frequent ESR1 methylation gene (p>0.05), Luminal A; ESR1 Methylation OS at 5 years 81% vs. 93% when was ESR1 Unmethylation. Luminal B; ESR1 Methylation 86% SG at 5 years vs. 92% in Unmethylation ESR1. Triple negative; ESR1 Methylation SG at 5 years 75% vs. 80% in unmethylation ESR1. HER2; ESR1 Methylation SG at 5 years was 66.7% vs. 75% in unmethylation ESR1. Conclusions: Gene promoter region hypermethylation is a significant event in primary breast cancer. However, its impact on tumor progression and potential predictive implications remain relatively unknown. Our study identifies the presence of variations in global levels of methylation promoters ESR1 genes in breast cancer with different phenotype classes and shows that these differences have clinical significance. Although numerous issues remain to be resolved, quantitative measurement of circulating methylated DNA may be of significance in the assessment and search of targeted therapy resistance related to ESR1 and HER2 status by epigenetic or transcriptional cancer therapy No significant financial relationships to disclose.
The impact of post-remission therapy on outcome of patients with poor-risk AIDS and secondary AML treated with intensive chemotherapy with or without stem cell transplantation in a joint study (CRIANT) of the EORTC, EBMT, SAK, HOVON, Scandinavian, and the Gimema leukemia groups
Authors: TM De Witte, A Hagemeijer, S Suciu, A Belhabri, Michel Delforge, C Aul, M Avaido, D Selleslag, H Schouten, H Biersack, A Ferrant, T Kovacsovics, P Muus, J Jansen, F Beeldens, A Gratwohl, U Hess, E Helstrom-Lindberg, P Wijermans, G Ossenkoppele, JP Marie, R Willemze, S Amadori
Journal: Blood (2003)
Effect of Sym004 on acquired resistance to cetuximab in colorectal cancer (CRC) in a novel mouse avatar model.
Authors: Deepak B. Vangala, Sven T. Liffers, Michael Pohl, Christian Teschendorf, Andrea Tannapfel, Wolff H. Schmiegel, Stephan Hahn
Journal: Journal of Clinical Oncology (2015)

3578 Background: Monoclonal antibodies against EGFR have shown improved survival for mCRC-patients in clinical trials. Unfortunately, virtually all patients acquire resistance to these agents during the course of treatment. Preclinical models of acquired resistance with close resemblance to the patient tumor are lacking. Sym004, a novel monoclonal anti EGFR antibody mixture has shown to overcome cetuximab (c-mab) resistance in HNSCC cell lines. Methods: Samples of 100 CRC patients undergoing surgery were implanted subcutaneously in nude mice. Treatment cohorts of 10 wildtype (WT for KRAS, BRAF, NRAS, PI3K) tumors and 3 tumors with either KRAS, BRAF or PI3K mutation respectively were generated for i.p. treatment with Sym004, c-mab (25mg/kg biw) or control. Primary observational period was 29 days. In case of response, treatment was continued until acquired resistance – defined as tumor doubling after primary observational period – arose. Results: Tumors with KRAS, BRAF or PI3K mutations were resistant to c-mab. All but two tumors with WT-status responded to c-mab and Sym004 during primary observational period (stable disease or tumor regression). Sym004 showed a significantly deeper response in 4 cases at day 29. Acquired resistance for c-mab developed in 4 tumors at days 33, 48, 60 and 71, respectively. In two of these cases tumor volume was stable with Sym004 and in the other two cases acquired resistance developed with substantial delay (d60 vs d33, d105 vs d60). Complete remission with c-mab and Sym004 occurred in two cases, one of which faster with Sym004 and lasting 100 days beyond end of treatment (c-mab: 10 days). Conclusions: Here, we present the first preclinical patient derived xenograft model of acquired resistance to anti-EGFR targeted therapy in CRC. We show that Sym004 is able to generate a deeper and prolonged response in 5 of 10 tested WT CRC patient derived tumors. This superior response rate of Sym004 suggests that clinical trials of Sym004 in CRC are warranted. Lastly, our successful proof of principle experiments for in vivo modeling of secondary resistance in CRC indicate that this strategy can serve as a testing platform for treatment optimization of targeted therapy addressing secondary resistance.
Real-world risk score for hepatocellular carcinoma risk prediction in CHBV: a validation outside of Asia
Authors: Mathias Daheim, Sonja Lang, Tobias Goeser, Hans-Michael Steffen, Münevver Demir
Journal: Gut (2016)

With great interest we have read the recent paper by Poh et al 1 suggesting the use of a routine parameter-based risk score for the development of hepatocellular carcinoma (HCC) in Asian patients with chronic HBV infection (CHBV).

With an estimated 240 million people being chronically infected by HBV worldwide, CHBV is a major global health burden, putting these people at risk for the development of liver cirrhosis and HCC.2–4

It remains challenging to identify those patients with CHBV carrying a high risk for HCC development applying an easy to use, readily available and cost effective test system. Therefore risk predicting …
Survival comparison analysis of two historical cohorts of metastatic renal cell carcinoma patients (cytokine therapy versus targeted agents): A European single-center experience over 26 years.
Authors: Georg C. Hutterer, Silvia V. Golbeck, Edvin Mrsic, Daniel Krieger, Angelika Bezan, Johanna Jesche, Karl Pummer, Richard Zigeuner, Martin Pichler
Journal: Journal of Clinical Oncology (2015)

513 Background: By the approval of new targeted agents in 2006, the standard of therapy in metastatic renal cell carcinoma (mRCC) changed, since they demonstrated significantly improved progression-free survival (PFS) rates compared with interferon in phase III clinical trials. Differences in overall survival (OS) could not be proven since many patients switched to another effective substance after progression of the disease. Thus, we compared two mRCC patient cohorts in order to detect OS differences between immunotherapy and targeted therapies in a real-life population outside controlled clinical trials. Methods: Clinico-pathological data from 594 mRCC patients, operated between 1984 and 2010 at a single tertiary academic center, were evaluated retrospectively with the null hypothesis, that there is no statistically significant difference in OS of patients treated either with interferon or targeted agents. Using electronical patient records, all data regarding the beginning, duration, lines, and different forms of therapies were assessed. Patients’ cancer-specific survival (CSS), as well as OS, were assessed using the Kaplan-Meier method, compared with the log-rank test. A first analysis revealed results for the entire study cohort. Subsequently, outcome analyses were restricted to mRCC patients with clear cell histology only. Results: With respect to the complete follow-up period, our results in both analyses did not show a statistically significant OS difference between the two therapy modalities. By limiting the observation period to 5 years after treatment initiation, a statistically significantly improved median five-year OS rate (26 mo.) for clear cell mRCC patients treated with targeted agents was observed, compared with 21 mo. in the interferon group (p=0.028). Conclusions: Our results confirm the presumption of an improved OS in mRCC attributable to treatments with targeted agents compared with previous cytokine therapies.
Outcomes of bivalirudin in moderate and high risk patients with acute coronary syndromes and renal insufficiency: An ACUITY substudy
Authors: Aiay J Kirtane, Roxana Mehran, George Dangas, Steven Manoukian, Frederick Feit, Thomas Stuckey, Magnus Ohman, Martial Hamon, Angel Cequier, David Cohen, Charles Pollack, James Hoekstra, Stuart Pocock, Bernard Gersh, Joseph Stella, Michel Bertrand, Walter Desmet, Gregg W Stone
Journal: Journal of the American College of Cardiology (2007)
Gene Expression Patterns Associated with Cytarabine Pharmacology and Outcome in Pediatric Acute Myeloid Leukemia.
Authors: Jatinder K. Lamba, Kristine Crews, Stanley Pounds, Xueyuan Cao, Varsha Gandhi, William Plunkett, Sharyn D. Baker, Ching-Hon Pui, Dario Campana, James R. Downing, Jeffrey Rubnitz, Raul C Ribeiro
Journal: Blood (2009)
Multifunctional “core-shell” nanoparticles-based gene delivery for treatment of aggressive melanoma
Authors: Ling Li, Linjiang Song, Xi Yang, Xia Li, Yuzhe Wu, Tao He, Ning Wang, Suleixin Yang, Yan Zeng, Li Yang, Qinjie Wu, Yuquan Wei, Changyang Gong
Journal: Biomaterials (2016)
Immunosuppression status of liver transplant recipients with hepatitis C affects biopsy-proven acute rejection
Authors: Jong Man Kim, Kwang-Woong Lee, Gi-Won Song, Bo-Hyun Jung, Hae Won Lee, Nam-Joon Yi, ChoonHyuck David Kwon, Shin Hwang, Kyung-Suk Suh, Jae-Won Joh, Suk-Koo Lee, Sung-Gyu Lee
Journal: Clinical and Molecular Hepatology (2016)

Background/Aims The relationship between patient survival and biopsy-proven acute rejection (BPAR) in liver transplant recipients with hepatitis C remains unclear. The aims of this study were to compare the characteristics of patients with and without BPAR and to identify risk factors for BPAR. Methods We retrospectively reviewed the records of 169 HCV-RNA-positive patients who underwent LT at three centers. Results BPAR occurred in 39 (23.1%) of the HCV-RNA-positive recipients after LT. The 1-, 3-, and 5-year survival rates were 92.1%, 90.3%, and 88.5%, respectively, in patients without BPAR, and 75.7%, 63.4%, and 58.9% in patients with BPAR (P<0.001). Multivariate analyses showed that BPAR was associated with the non-use of basiliximab and tacrolimus and the use of cyclosporin in LT recipients with HCV RNA-positive. Conclusion The results of the present study suggest that the immunosuppression status of HCV-RNA-positive LT recipients should be carefully determined in order to prevent BPAR and to improve patient survival. Keywords: Hepatitis C virus; Immunosuppression; Rejection; Outcome; Calcineurin antagonists; Tacrolimus
Copy-number analysis identified new prognostic marker in acute myeloid leukemia
Authors: O Nibourel, S Guihard, C Roumier, N Pottier, C Terre, A Paquet, P Peyrouze, S Geffroy, S Quentin, A Alberdi, R B Abdelali, A Renneville, C Demay, K Celli-Lebras, P Barbry, B Quesnel, S Castaigne, H Dombret, J Soulier, C Preudhomme, M H Cheok
Journal: Leukemia (2016)
A phase III clinical trial of neoadjuvant chemoradiotherapy followed by surgery versus surgery alone for locally advanced squamous cell carcinoma of the esophagus.
Authors: Hong Yang, Jianhua Fu, Mengzhong Liu, Wentao Fang, Jiaming Wang, Yuping Chen, Zhijian Chen, Chengchu Zhu, Jiaqing Xiang, Huanjun Yang, Zhengtao Yu, Qingsong Pang, Weimin Mao, Xiao Zheng, Yongtao Han
Journal: Journal of Clinical Oncology (2014)

TPS4146 Background: Surgery is the main treatment of esophageal squamous cell carcinoma (ESCC), but the prognosis of patients with locally advanced ESCC is rather poor. Preoperative chemoradiotherapy followed by surgery seems to hopefully improve the survival of ESCC. Nevertheless, the results of different studies were inconsistent. We are to carry out a phased III clinical trial to investigate the effect of this multidisciplinary therapy for the overall survival of patients with locally advanced ESCC. Methods: This study is a multi-centered randomized controlled phase III clinical trial. According to Sixth Edition AJCC Cancer Staging, patients with IIB-III staged squamous cell carcinoma of the thoracic esophagus are randomly allocated to either preoperative chemoradiotherapy followed by surgery (arm A), or surgery alone(arm B). The intended number of randomized patients will be 430, 215 per arm. In the arm A, Chemotherapy and radiotherapy are performed concurrently. Patients received two cycles of vinorelbine and cisplatin. Vinorelbine at 25 mg/m2 per day is administered in bolus infusion on d1, d8, d22 and d29. Cisplatin at 75 mg/m2 is administered by intravenously infusion on d1 and d22 (or 25 mg/m2days 1 to 4 and 22 to 25). A total radiotherapy dose of 40 Gy is delivered in 20 daily fractions of 2.0 Gy each (given 5 d/wk for 4 weeks). McKeown esophagectomy or Ivor Lewis esophagectomy will be performed 4-6 weeks after chemoradiotherapy. Two-field lymphadenectomy with total mediastinal lymph node dissection is performed during sugery. Primary outcomes are 3 and 5 years overall survival. From 2007 July to 2013 December, over 300 eligible patients were randomly assigned in eight cooperative cancer centers. The patient enrollment will be completed in 2014. Clinical trial information: NCT01216527.
Aberrant Autocrine and Paracrine CD40L Signaling Promotes Primary Myeloma Cell Survival and Attenuates Bortezomib-Induced Apoptosis.
Authors: Selina Chen-Kiang, Scott Ely, Maurizio Di Liberto, Kaida Wu, John Shaughnessy, Malcolm Moore, Ruben Niesvizky, Eunice Hatada
Journal: Blood (2005)
“Comitato ospedale senza dolore”: a successful strategy
Authors: K.F. Borgonovo, M. Cabiddu, F. Petrelli, A. Coinu, M. Ghilardi, A. De Giuseppe, M. Destro, G. Dognini, G. Locatelli, G. Sgroi, L. Turati, F. Steccanella, L. Invernizzi, A. Ghedi, C. Ercole, S. Barni
Journal: Annals of Oncology (2015)
1PD A high throughput compound screen identifies potential combinations to overcome resistance to Cdk2 inhibitors in Cyclin E1 amplified high grade serous ovarian cancer
Authors: G. Au-Yeung, F. Lang, C. Mitchell, K. Jarman, K. Lackovic, C. Cullinane, L. Mileshkin, D. Rischin, D. Etemadmoghadam, D. Bowtell
Journal: Annals of Oncology (2015)
Relation of specific urinary amino acids to blood pressure: Findings from the INTERMAP study
Authors: Martha L Daviglus, Jeremiah Stamler, Lucila Blanco-Cedres, Paul Elliott, Hugo Kesteloot, Peter Declercq, Queenie Chan, Ka He, Daniel B Garside, Xuan Cai, Hirotsugu Ueshima, Beifan Zhou, Alan R Dyer
Journal: Circulation (2006)
Increased circulating level of the autocrine growth factor GP88 (PC cell-derived growth factor factor/progranulin) in early- and advanced-stage non-small cell lung cancer and small cell lung cancer.
Authors: Q. W. Gai, M. J. Edelman, D. Ecklund, B. Yue, S. Kamimura, D. Hawkins, M. N. Horiba, R. Battafarano, G. Serrero
Journal: Journal of Clinical Oncology (2010)

e18103 Background: GP88, is an 88 kDa glycoprotein autocrine growth factor belonging to a newly identified family of growth modulators characterized by unique cysteine-rich motif and playing a role in the proliferation and survival of human cancers by inhibiting apoptosis, stimulating cell migration and invasiveness, and promoting metastasis. In vitro and in vivo studies have examined the biological activity and expression of GP88 in human breast cancer. In particular, pathological and clinical studies investigating the expression of GP88 in lesions and sera from breast cancer patients demonstrated GP88 expression was associated with clinically poor prognosis. The current study evaluated GP88 in lung cancer. Methods: 28 patients newly diagnosed with SCLC or NSCLC or previously diagnosed lung cancer and undergoing chemotherapeutic regimen change were enrolled. 20 healthy adults with similar background, including history of smoking, were enrolled as control group. Venous blood was collected and serum GP88 was tested by human GP88 ELISA. Results: 28 patients enrolled. 6 SCLC (1 Limited stage SCLC, five extended stage SCLC). 22 NSCLC, stage IV: 16, stage III: 3 and stage I: 3. The mean serum GP88 level in the lung cancer study group was 46.5 ± 15.5 ng/mL while the mean serum GP88 level in the control group was 28.4 ± 5.6 ng/mL, p = 0.0004 (Wilcoxon rank sum test). Conclusions: In patients diagnosed with SCLC/NSCLC, there is a statistically significant increase of serum GP88. Further studies will be planned to explore the role of GP88 as a biomarker for diagnosis and prognosis of lung cancer. We are currently accruing additional pts and analyzing whether GP88 has prognostic or predictive value. No significant financial relationships to disclose.
What we could know from the semiannually repeated screening with low-dose helical CT in a high-risk cohort over 10 years: Update of Anti-Lung Cancer Association project
Authors: N. Seki, K. Eguchi, M. Kaneko, H. Ohmatsu, R. Kakinuma, E. Matsui, M. Kusumoto, T. Tsuchida, H. Nishiyama, N. Moriyama
Journal: Journal of Clinical Oncology (2007)

7568 Background: There have been several randomized trials of low-dose helical CT (LDCT) screening for lung cancer. However, all trials are in progress. Therefore, before they are completed, we summarized what we could know from an update of Anti-Lung Cancer Association project, which was regarded as a longer-term study with LDCT performed at shorter intervals and with a larger number of detected cancers than any other single-armed studies. Methods: Among 2,120 participants, 1,877 (mean age 64 years, 88% male, and 84% smoker) underwent semiannually repeated screening from 1993 to 2004 (median, 3.5 years). We investigated (1) survival of patients with screening detected lung cancers, (2) presence of a stage shift (indicator of a mortality benefit), (3) appropriate duration of repeated screening, (4) identification of high-risk group by age, sex, and smoking, and (5) appropriate screening intervals by high-risk group (6 months or 1 year). Results: (1) The 5- and 10-year survival rates were 84.5% and 84.5%, respectively, in repeated screening group (n = 57) and were 68.7% and 38.1%, respectively, in initial screening group (n = 19) (P = 0.208). (2) Only in invasive adenocarcinoma, both proportion of stage II to IV and tumor size were negatively correlated with duration of repeated screening (r = −0.77, P = 0.007 and r = − 0.60, P = 0.029, respectively). (3) Detection rate of all incidence cancers were positively correlated with duration of repeated screening (r = 0.50, P = 0.020). However, detection rate remained unchanged until 5 years of repeated screening. Moreover, stage shift did not occur until 5 years of repeated screening. (4) Female sex (HR 2.9, P = 0.015) and smoking (HR 2.7, P = 0.046) were demographic risk factors for lung cancer detection at repeated screening. The accumulated 10-year detection rates for female smokers (n = 91), male smokers (n = 1,557), and non-smokers (n = 229) were 15.1%, 6.2%, and 4.3%, respectively (P = 0.002). (5) The estimated relative cancer detection powers of annual screening to semiannual screening were 50% and 57% for female and male smokers with lung cancer, respectively. Conclusions: Semiannually repeated LDCT screening over 5 years might be beneficial to smokers, especially female smokers. No significant financial relationships to disclose.