tbuckley/cabot-search huggingface dataset:
A phase I/II randomized study of Debio1143 combined with concurrent chemoradiation therapy (CCRT) in patients with locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN).
Authors: Christophe Le Tourneau, Yungan Tao, Jean-Pierre Delord, Silvano Brienza, Gregoire Vuagniaux, Marie-Paule Sablin, Claudio Zanna, Jean Bourhis
Journal: Journal of Clinical Oncology (2014)

TPS6097^ Background: Inhibitors of apoptosis proteins (IAPs) are negative modulators of apoptosis which represent attractive targets to overcome resistance to cancer therapy. The small molecule Debio1143 is a potent orally-active IAP antagonist able to promote apoptosis in tumour cells by restoring caspase activity, and modulating NF-κB signalling and TNFα effects. As single agent, Debio1143 inhibits cell growth and induces apoptosis in a subset of human cancer cell lines and in multiple xenograft models of human cancer, including SCCHN. Furthermore, Debio1143 potentiates the effects of cisplatin and radiotherapy in SCCHN nonclinical models (D. Viertl et al.,Radiotherapy and Oncol 106, Suppl.1, 2013; Abstract OC-19, p. 56). Debio1143 monotherapy was well toleratedin cancer patients up to 900 mg OD, resulted in rapid and sustained cIAP1 suppression in patient peripheral blood mononuclear cells and in skin biopsies, and achieved exposures that were previously shown to be active in animal models (H. Hurwitz et al., EJC 48, Suppl.6, 2012; Abstract 76, p. 25). Methods: This is a phase I/II, multicentre study comprising a dose-escalation Phase I part (A) and a randomised Phase II part (B) that enrols untreated LA-SCCHN patients with T≥2, N0-3, M0 disease eligible for exclusive chemoradiation. Oropharynx cancer patients have to be HPV-negative. Standard fraction radiotherapy is delivered with a daily dose of 2Gy for 5 days per week to a total dose of 70Gy. Cisplatin is administered on Day 2 of every 21-day cycle for 3 cycles at the dose of 100 mg/m². Debio1143 is orally administered OD on days 1-14 of every 21-day cycle. The starting dose is 100 mg and will be in part A escalated by 100 mg increase using a modified continual reassessment method. Extensive PK, PD, and pharmacogenomics assessments are included. Part B is a double-blind, placebo-controlled Phase II trial in which 97 patients will be randomised to receive placebo or Debio1143 at the dose recommended in part A in combination with CCRT. Primary endpoint is locoregional control at 18 months. Dose escalation started on September 2013 and it is ongoing. Clinical trial information: NCT02022098.
Frequent Instability of Type I and II Aberrations Between Diagnosis and Relapse Observed in Pediatric Aml; Implications for Targeted Therapy and MRD Detection.
Authors: Costa Bachas, Gerrit-Jan Schuurhuis, Iris H.I.M. Hollink, Bianca F. Goemans, Dirk Reinhardt, Christian M Zwaan, Marry M. van den Heuvel, Eveline S.J.M de Bont, Elisabeth R. Van Wering, Gertjan Kaspers, Jacqueline Cloos
Journal: Blood (2009)
P3-268: Clinico–pathological features of resected lung cancer in Niigata prefecture: registry report of 3306 cases during 5 years
Authors: Masanori Tsuchida, Teruaki Koike, Ken-Ichi Togashi, Takehiro Watanabe, Masatomo Yazawa, Jun-Ichi Hayashi
Journal: Journal of Thoracic Oncology (2007)
Long non-coding RNAs in the regulation of myeloid cells
Authors: Xinyu Tian, Jie Tian, Xinyi Tang, Jie Ma, Shengjun Wang
Journal: Journal of Hematology & Oncology (2016)

Long non-coding RNAs (lncRNAs) have been attracting immense research interests. The relevance of lncRNAs in biological and physiological as well as in pathological processes has increased along with the understanding of their various regulatory mechanisms. Abundant studies have indicated that lncRNAs are involved in the differentiation, proliferation, activation, and initiation of apoptosis in different cell types. However, most studies about the regulating biology of lncRNAs are currently focused on cancer cells. This review is focused on the widely unexplored role of lncRNAs in the cell fate of myeloid cells. In this review, we summarize recent studies that have confirmed lncRNAs to be essential in the development of myeloid cells under normal and pathological conditions.
Topotecan and cladribine with filgrastim support in relapsed, refractory and poor prognosis leukemias: A phase I-II study
Authors: L. R. Silverman, L. Isola, R. Brenner, J. Gabrilove, J. Mandeli
Journal: Journal of Clinical Oncology (2004)

6724 Background:Patients (pts) with an antecedent hematopoietic disorder (AHD) prior to AML or with relapsed or refractory leukemias have a poor prognosis. Standard regimens are generally not curative. Topotecan, has shown activity in hematologic malignancies. It binds to topoisomerase I which results in DNA degradation and may trigger the apoptotic pathway. Cladribine (CDA), induces apoptosis in a number of malignant cell lines with effects on both dividing and quiescent cells. Responses occurred in up to 47% of pts with AML at high doses ranging up to 21 mg/m2/d with neuropathy as the dose limiting toxicity (DLT). Filgrastim (G-CSF) has reduced the frequency of infection and duration of neutropenia in pts with AML undergoing chemotherapy. Methods:Pts with poor prognosis AML or relapsed or refractory ALL, with acceptable hepatic/renal function, were entered into cohorts (3 pts/cohort) of escalating doses of topotecan and CDA each administered as a 5 day continuous infusion, according to a modified fibonacci sequence: Results: Among 24 pts entered 15 (63%) were female, 9 (37%) male with median age 61 yrs; 10 (42%) had AHD; 4 (17%) secondary AML, 13 (54%) relapsed AML, and 2 (8%) relapsed ALL. Responses occurred in 7 (35%) of 20 evaluable pts: 4 CR, 1 CRp, 2 PR, 13 NR and 4 inevaluable. Duration of response ranged up to 22 months. No grade 4 non-hematologic toxicities were identified. Grade 4 cytopenias occurred in all. One pt in cohort 5 had persistent marrow hypoplasia at day 34 and succumbed to sepsis on day 48, potentially representing a DLT. Treatment associated mortality (TAM) is 12%. Conclusions:The combination is well tolerated and appears active. The TAM is well within the range reported in this heavily treated population. Once an MTD is established, incorporation of this regimen as a component of other treatment strategies should be explored. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline Amgen GlaxoSmithKline; Ortho Biotech; Amgen
Hematopoietic Stem Cell Mobilization for Gene Therapy: The Combination of G-CSF+Plerixafor in Patients with Beta-Thalassemia Major Provides High Yields of CD34+ Cells with Primitive Signatures
Authors: Elena Baiamonte, Rita Barone, Rosalia Di Stefano, Melania Lo Iacono, Barbara Spina, Flavia Contino, Rosario Di Maggio, Massimiliano Sacco, Angela Vitrano, Salvatore Feo, Aurelio Maggio, Santina Acuto
Journal: Blood (2015)
SAT0325 Changes in the Pattern of Death in Systemic Sclerosis: Table 1
Authors: M. Rubio-Rivas, V. Fonollosa-Pla, X. Corbella-Virόs, C. Tolosa-Vilella, D. Colunga-Argüelles, M.V. Egurbide-Arberas, J.A. Vargas-Hitos, J.J. Ríos-Blanco, L. Trapiella-Martínez, C.P. Simeόn-Aznar
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Visceral involvement treatment and prognosis has changed in the latest years, influencing somehow the pattern of death. <h3>Objectives</h3> To demonstrate changes in the pattern of death in patients with Systemic Sclerosis in the latest 3 decades in the Spanish cohort. <h3>Methods</h3> 1135 patients with Systemic Sclerosis have been retrospectively assessed from the Spanish Scleroderma Registry (RESCLE). <h3>Results</h3> See Table 1 <h3>Conclusions</h3> – The rate of SSc-related death is decreasing in the latest 2 decades – There9s a larger percentage of pulmonary death – There9s a lower percentage of renal death – Renal death is present mainly in the first 5 years after diagnosis and in patients with the difuse subtype. <h3>References</h3> Steen V.D., Medsger T.A. Changes in causes of death in systemic sclerosis, 1972-2002. Ann Rheum Dis 2007; 66:940-4. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1762
Nivolumab (anti-PD-1; BMS-936558, ONO-4538) and ipilimumab in first-line NSCLC: Interim phase I results.
Authors: Scott Joseph Antonia, Scott N. Gettinger, Laura Quan Man Chow, Rosalyn A. Juergens, Hossein Borghaei, Yun Shen, Christopher Harbison, Allen C. Chen, Neal Ready, Naiyer A. Rizvi
Journal: Journal of Clinical Oncology (2014)

8023 Background: Nivolumab, a fully human IgG4 programmed death-1 (PD-1) immune checkpoint inhibitor antibody, and ipilimumab, an IgG1 CTLA-4 checkpoint receptor blocking antibody, have shown activity in advanced NSCLC; clinical data in melanoma showed improved responses and a manageable safety profile when combined. We report interim results from a phase I study evaluating first-line nivolumab + ipilimumab (N+I) in advanced NSCLC patients (pts). Methods: Chemotherapy-naive pts (n=46) with squamous (sq) or non-sq NSCLC received the 3 + 1 mg/kg or 1 + 3 mg/kg combination dose IV Q3W for 4 cycles followed by nivolumab 3 mg/kg IV Q2W until progression/unacceptable toxicity. Objective response rate (ORR; RECIST 1.1) was evaluated overall and by baseline tumor PD-L1 status (Dako immunohistochemistry assay). After an amendment, a 1 + 1 mg/kg cohort was added (n=30, data immature at Dec 2013 analysis). Results: In the 4 cohorts with ≥4 months follow up, any-grade treatment-related adverse events (managed with protocol algorithms) were reported in 39 pts (85%; grade 3–4 in 22 pts [48%]) and led to discontinuation in 16 pts. Treatment-related deaths (n=3) were due to respiratory failure, bronchopulmonary hemorrhage and toxic epidermal necrolysis. Responses occurred in all 4 cohorts (Table); overall ORRb was 22% (median duration of response [mDOR] not reached [NR]) and stable disease (SD) 33% (range 13 – 34.1+ wks); 2 pts exhibited unconventional "immune related" responses. In 29 evaluable tumor samples from the study, ORR did not correlate with PD-L1 status. Conclusions: These interim data in pts with advanced NSCLC suggest that a nivolumab + ipilimumab immunotherapy regimen is feasible and demonstrates antitumor activity in both PD-L1+ and PD-L1– pts. Safety will be further assessed at the 1 + 1 mg/kg dose. The recommended combination dose for phase II/III evaluation has not been determined. Clinical trial information: NCT01454102. N1 + I3 Sq N1 + I3 Non-sq N3 + I1 Sq N3 + I1 Non-sq N 7 15 8 16 ORR,a n (%) 1 (14) 1 (7) 2 (25) 2 (13) ORR,b n (%) 1 (14) 2 (13) 3 (38) 4 (25) 3 (14) 7 (29) SD, n (%) 2 (29) 6 (40) 4 (50) 3 (19) mDOR (Kaplan-Meier),a wk (range) NR (9+) NR (21+) 17 (12, 21) NR (24+, 25+) Ongoing responders,a n (%) 1 (100) 1 (100) 0 2 (100) a Confirmed OR only. b Confirmed + unconfirmed OR.
A MULTICENTER, DOUBLE-BLIND, PLACEBO-CONTROLLED, RANDOMIZED PHASE 2 STUDY OF GANITUMAB OR RILOTUMUMAB WITH PLATINUM-BASED CHEMOTHERAPY AS FIRST-LINE TREATMENT FOR EXTENSIVE-STAGE SMALL-CELL LUNG CANCER (SCLC)
Authors: Bonnie Glisson, Andrzej Kazarnowicz, Kristiaan Nackaerts, Sergey Orlov, Rodryg Ramlau, Benjamin Besse, Manuel Cobo Dols, Hari Menon, Luis Paz-Ares Rodriguez, Yilong Zhang, Min Zhu, Yizhou Jiang, Elwyn Loh, Jennifer Gansert, Sarita Dubey
Journal: Journal of Thoracic Oncology (2013)
Nitroflurbiprofen (HCT-1026), a nitric oxidereleasing cyclooxygenase-inhibitor, improves cirrhotic portal hypertension in the rat without major side-effects
Authors: Wim Laleman, Lien Van Landeghem, Ingrid Vander Elst, Marcel Zeegers, Johan Fevery, Frederik Nevens
Journal: Hepatology (2006)
Web-based communication between cancer patients and their supporting community compared to spoken communication: An analysis of the MyLifeLine.org cancer foundation user survey.
Authors: R. E. Fisher
Journal: Journal of Clinical Oncology (2010)

e19639 Background: The MyLifeLine.org Cancer Foundation provides free, confidential Web-based communication for cancer patients to correspond with their supporting community. The Foundation has been providing this service since 2007. Methods: The Foundation conducted a survey of its active users in October, 2009. Questions were submitted by email to the user database, and response to the questionare was voluntary. Of 611 active users, 102 surveys were submitted. Besides demographic questions, users were asked questions regarding quality of communication. Results: The survey found that 92% of users felt that use of the website for communication kept their supporting community updated as to their status during cancer treatment. Results showed that 73% of users found that this Web-based communication reduced the burden of phone calls. Ninety-four percent of respondents reported that fewer phone calls improved their cancer treatment recovery. Eighty-six percent found that the website system increased contact between the cancer patient and their supporters. Eighty-two percent found this system improved their communication with their supporters, as compared to using other potential forms of communication. Conclusions: This Web-based form of communication between cancer patients and their supporters provides more recovery for cancer patients compared to other communication methods, and still improves support through communication. In addition, the system offers a more profound level of communication than other, more traditional forms of communication. Written communication as in this system allows for more depth of expression, which fosters the healing process in cancer treatment. No significant financial relationships to disclose.
Obesity and hepatocellular carcinoma in patients receiving entecavir for chronic hepatitis B
Authors: Jaemin Lee, Sun Hong Yoo, Won Sohn, Hyung Woo Kim, Yong Sun Choi, Jung Ho Won, Jin Young Heo, Sang Jong Park, Young Min Park
Journal: Clinical and Molecular Hepatology (2016)

See the commentary-article "Does obesity increase the risk of hepatocellular carcinoma in chronic hepatitis B patients?" on page 336.
Health-related quality of life in patients with advanced renal cell carcinoma receiving pazopanib or placebo in a randomized phase III trial.
Authors: A. S. Pickard, D. Cella, M. S. Duh, A. Guerin, N. Mishagina, L. Antràs, M. Neary, L. McCann, R. Hodge, C. Sternberg
Journal: Journal of Clinical Oncology (2011)

9096 Background: In a double-blind, randomized Phase III trial of patients with advanced renal cell carcinoma, pazopanib 800mg QD (n=290) significantly prolonged progression-free survival (PFS) compared to placebo (n=145; median PFS, 9.2 vs. 4.2 months, hazard ratio [HR]=0.46, 95% confidence interval [CI] 0.34-0.62, p-value<0.0001), with no important difference in health-related quality of life (HRQoL) compared to placebo. This post-hoc analysis evaluated time to HRQoL decline by treatment group and whether tumor response/stabilization was associated with HRQoL benefit. Methods: HRQoL was assessed using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30) and EQ-5D index and visual analog scale (VAS). Effect of pazopanib on time to ≥20% decline from baseline HRQoL was estimated for all patients and by prior treatment (treatment-naïve vs. cytokine-pretreated). HRQoL changes were stratified by best response (based on Response Evaluation Criteria in Solid Tumors) during best response period (best response to progression) and compared: complete response (CR) or partial response (PR) vs. progressive disease (PD); stable disease (SD) vs. PD. Comparisons were for all patients and by treatment arm. Sensitivity analyses were conducted for different HRQoL deterioration thresholds. Results: There was a trend for pazopanib vs. placebo patients to be less likely to experience ≥20% HRQoL decline in QLQ-C30 global QOL scale (HR=0.77; 95% CI 0.57-1.03, p=.0817). Results by prior treatment and different HRQoL decline thresholds were similar. Patients with CR/PR experienced significantly less HRQoL deterioration to a meaningful extent compared to PD patients (adjusted difference, QLQ-C30: 11.8; 95% CI 7.1 - 16.5, p<0.001; EQ-5D index: 0.15; 95% CI 0.09 – 0.21, p<0.001; EQ-5D VAS: 10.8; 95% CI 5.7-16.0, p<0.001); mean differences exceeded previously established minimally important differences. Results were similar across treatment arms. Conclusions: Results support the acceptable tolerability profile of pazopanib and suggest patients who had tumor response also experienced better HRQoL compared to those without response.
Effects of Ontogeny, Ethnicity, Gender and Loss of Companion Cells on Ex-Vivo Expansion of Erythroid Cells for Transfusion
Authors: Valentina Tirelli, Francesca Masiello, Massimo Sanchez, Barbara Ghinassi, Carolyn Whitsett, Giovanni Migliaccio, Anna Rita F Migliaccio
Journal: Blood (2011)
Follow-up results after 9 years (yrs) of the ongoing, phase II B2222 trial of imatinib mesylate (IM) in patients (pts) with metastatic or unresectable KIT+ gastrointestinal stromal tumors (GIST).
Authors: M. von Mehren, M. C. Heinrich, H. Joensuu, C. D. Blanke, E. Wehrle, G. D. Demetri
Journal: Journal of Clinical Oncology (2011)

10016 Background: B2222 was the first large trial to show that 1st-line IM induces high objective response rates and durable disease control in pts with advanced GIST. Sequential study extensions allowed for ongoing IM treatment and extended pt follow-up, enabling evaluation of long-term survival and potential markers of disease control. Methods: Pts with advanced KIT+GIST were enrolled in an open-label, multicenter trial and randomized 1:1 to receive 400 or 600 mg/d IM. The original 3-yr study was serially extended to treat pts, who continued IM for >10 yrs, and to monitor long-term overall survival (OS) and progression-free (TTP) rates. Results: Of 147 pts initially enrolled between July 2000 and April 2001, 56 continued IM therapy beyond 3 yrs. Maximum follow-up time for this analysis was 9.9 yrs (median 9.4 yrs). As of May 26, 2010, 26 pts (17.7%) remained on continuous IM since study entry; the GIST genotypes were: KIT exon 11 mutant (m), n=16; KIT exon 9 m, n=3; PDGFRA m, n=1; wild type, n=1; and unknown, n=5. Twenty-one of 30 pts (70%) withdrew during extensions, due to GIST progression (PD). The estimated TTP rate at 9 yrs for all 147 pts was 14%; this was similar for pts with complete or partial response (CR/PR, 16%) or stable disease (SD, 17%) as best overall response. The estimated 9-yr OS rate for all pts was 35%: 38% for those with CR/PR; 49% for SD; 0% for PD. Estimated 9-yr TTP rates by tumor bulk at baseline according to quartiles were: 29% in group 1 (<39.1 mm2), 11% in group 2 (39.1 – <102.1 mm2), 13% in group 3 (102.1 – <262.6 mm2), and 3% in group 4 (≥262.6 mm2). Of the pts who entered the extension study, 53.6%, 23.1%, 11.5%, and 11.5% from groups 1 to 4, respectively, remain on study. Estimated 9-yr OS rates by tumor bulk were 58%, 40%, 20%, and 23% in the 4 groups, respectively. Although safety was not captured systematically beyond 3 yrs, no unexpected long-term toxicities were observed, and IM remained well tolerated. Conclusions:A meaningful subset of pts with advanced GIST survived ≥9 yrs with 1st-line IM therapy. Pts with SD or CR/PR showed similar estimated 9-yr OS and TTP rates. Low tumor bulk at baseline predicted for longer TTP and improved OS.
Is breast cancer in women with L-thyroxine supplemented hypothyroidism a less aggressive disease? Retrospective evaluation of risk reduction and clinico-pathological differences
Authors: S. Thakur, A. Hercbergs, H. A. Daw, H. L. Farag
Journal: Journal of Clinical Oncology (2008)

22048 Background: A putative association between thyroid function and breast cancer [BC] risk is controversial but retrospective studies suggest a protective effect of hypothyroidism [HYP] in BC. Growing pre-clinical evidence indicates that in cancer thyroid hormone (TH) is mitogenic, anti-apoptotic and pro-angiogenic acting via genomic and non-genomic mechanisms e.g. aνβ-3 integrin. The potential impact of TH on prognosis in cancer therefore requires elucidation since L-thyroxine (L-thy) supplementation in hypothyroid cancer patients might constitute a prognostic variable. Methods: 2,044 electronic and paper charts were reviewed in a hospital based retrospective case-control study on 159 female patients with AJCC stage 1–4 invasive BC patients (infiltrating ductal (129), lobular (19) carcinoma- the majority) over 10 year. 68 cases of invasive BC with primary HYP (on L-thy supplementation) were compared to 91 matched controls -i.e. age, baseline socio-demographics, history of (h/o) estrogen replacement, family h/o BC, pregnancy, body mass index, and menarche. Differences in age of diagnosis, survival and clinic-pathological variables were analyzed. TH blood levels and L-thy dosage were generally unavailable. Chi-square, fisher's exact test and the Wilcoxon 2 sample tests were applied for analysis on SAS 9.0 statistical software program. Results: Compared to euthyroid patients those with HYP were diagnosed with breast cancer 4.7 years later (mean age at diagnosis 68.12 vs. 63.44 years, p <0.035).The tumor measured less than 1 cm in 27.4% of HYP vs. 11.4% of euthyroid patients, p <0.047. HYP patients were also less likely to have lymph node involvement (21.6 vs. 40.5, p <0.28) and more likely to have low S phase fraction (79.4 vs. 60.4, p <0.21). There was insufficient data for thyroid function correlation and survival analysis. Conclusions: This study suggests that in women with L-thyroxine supplemented HYP, breast cancer is diagnosed over 4 ‘asymptomatic’ years later than in a euthyroid cohort and is a less aggressive disease. Prospective studies are required to confirm these findings but in the interim we suggest caution in the TH supplementation of hypothyroid BC patients per ATA consensus guidelines. No significant financial relationships to disclose.
Active Receptor Editing in Chronic Lymphocytic Leukemia B-Lymphocytes - Analysis of Immunoglobulin Light Chain Genes and Kappa Deleting Element Rearrangements.
Authors: Miroslaw Majewski, Monika Lewandowska, Hanna Makuch-Lasica, Grazyna Nowak, Iwona Solarska, Iwona Kania, Krzysztof Warzocha
Journal: Blood (2006)
Fraud Not a Primary Cause of Irreproducible Results: A Reply to Clark et al.
Authors: Timothy H. Parker, Wolfgang Forstmeier, Julia Koricheva, Fiona Fidler, Jarrod D. Hadfield, Yung En Chee, Clint D. Kelly, Jessica Gurevitch, Shinichi Nakagawa
Journal: Trends in Ecology & Evolution (2016)
Molecular Follow-Up of Patients Treated with HSV-TK/ΔLNGFR Engineered Donor Lymphocytes after Allogeneic Stem Cell Transplantation.
Authors: Chiara Bonini, Zulma Magnani, Alessandra Recchia, Fabrizia Urbinati, Sara Muraro, Serenella Sartori Tech, Fabio Ciceri, Massimo Bernardi, Alessandra Pescarollo, Corrado Gallo-Stampino, Marco Bregni, Claudio Bordignon, Fulvio Mavilio
Journal: Blood (2004)
Epidemiology and 15-Year Follow up after Cladribine Treatment of Patients with Hairy Cell Leukemia (HCL): Population-Based Swedish Data and Long-Term Follow-up of Scandinavian Study Patients Identify Older Patients with Poorer Outcome
Authors: Henrik Samuelsson, Dag Heldal, Mats Jerkeman, Gunnar Juliusson
Journal: Blood (2008)
RADIATION-INDUCED LUNG DAMAGE QUANTIFICATION WITH CT SCANS: CORRELATION WITH SINGLE NUCLEOTIDE POLYMORPHISMS
Authors: Dirk De Ruysscher, Hoda Sharifi, Wouter Van Elmpt, Katrien Vandecasteele, Philippe Lambin, Yolande Lievens, Wilfried De Neve, Kim De Ruyck
Journal: Journal of Thoracic Oncology (2013)