tbuckley/cabot-search huggingface dataset:
A case report of sarcoma regression in a patient with MDS treated with lenalidomide
Authors: J. M. Shammo, M. Kassar, I. Robin, R. Knight
Journal: Journal of Clinical Oncology (2007)

20535 Background: Lenalidomide is an immunomodulatory drug recently approved for the treatment of MDS patients with del 5q cytogenetic abnormality. Here we describe a case of sarcoma regression in a patient with MDS who had been treated with lenalidomide. Method: An 84 year old man was diagnosed with low risk MDS in November 2002, he was transfusion dependent requiring 2–4 units of blood a month. He was enrolled on the MDS 002 trial in February 2004. He became transfusion independent by cycle 4. Results: In March 2005 he developed abdominal pain and a CT of the abdomen revealed a 2 x 2 cm mass involving the lesser curvature of the stomach. An MRI of the abdomen followed, confirming the presence of an enhancing gastric lesion, a biopsy of the mass revealed low grade malignant sarcoma. The patient was a poor surgical candidate and the decision was made to follow the progression of the mass with repeat imaging. In October 2005 a repeat MRI failed to visualize the previously noted mass, a recent CT performed in December 2006 was also negative for the presence of the mass. A potential therapeutic role for lenalidomide in this case which may have led to the regression of the sarcoma is possible although spontaneous regression can not be ruled out. It is not known if the mass was present at the time of enrollment on the clinic trial, it is also not clear as to why the patient presented with abdominal pain several months into the clinical trial. There had been several case reports in the literature describing similar results with thalidomide in patients with soft tissue sarcoma however, to our knowledge this clinical observation has never been reported with lenalidomide previously. Conclusion: This observation merits consideration for prospectively evaluating the efficacy of lenalidomide in patients with sarcoma for whom limited therapeutic options currently exist. No significant financial relationships to disclose.
Tamoxifen (T) compared to placebo (P), after adjuvant chemotherapy (CT), in premenopausal women with early breast cancer (EBC): Interim results of NCIC-CTG MA.12
Authors: V. H. Bramwell, K. I. Pritchard, D. Tu, K. Tonkin, H. Vachhrajani, J. Robert, A. Arnold, T. Vandenberg, B. Graham, L. Shepherd
Journal: Journal of Clinical Oncology (2007)

547 Background: In the early 1990’s, the role of adjuvant T in premenopausal women with EBC had not been clearly established. The efficacy of adjuvant T in hormone receptor (H) negative EBC was unclear. Methods: Eligible premenopausal women with node (N) +ve/high risk N -ve EBC, any H status, post surgery, received standard adjuvant CT (AC ×4, CMF ×6, CEF x6) then were randomized to T (20 mg/day) or P for 5 yrs. Overall survival (OS), disease-free survival (DFS) and toxicity/compliance were evaluated. Original sample size was 800 pts but based on slow accrual was reduced to 660. Mortality rate is lower than anticipated, and Data Safety Monitoring Committee approved reporting results after second interim analysis (152 deaths). Results: 1993–2000, 672 women randomized, median follow-up 8.4 yrs. For T vs P, 5 yr OS 87% vs 82% [Hazard Ratio HR 0.81 (95% CI 0.58–1.12), p = 0.19] and 5 yr DFS 78% vs 71% [HR 0.79 (95% CI 0.61–1.03), p = 0.09]. HR for OS (0.87 vs 0.78, p = 0.71) and DFS (0.79 vs 0.77, p = 0.87) were not significantly different for H +ve and H -ve tumors respectively. Compliance with T/P was suboptimal, 29% women stopping treatment within 2 yrs, and only 53% completing 5 yrs. Conclusions: Current results show only a trend towards improved DFS for premenopausal women with EBC who receive T after adjuvant CT. Other studies of similar design have shown improved DFS, but not OS, and meta-analysis may be more informative. Issues affecting results (slow accrual, improved outcomes for EBC, poor compliance, additional therapies) will be discussed. [Table: see text] [Table: see text]
GW26-e0229 Sinus of Valsalva aneurysm extending into left ventricle: combined diagnosis of conventional and live three-dimensional echocardiography
Authors: Wenjing Zhang, Mingxing Xie, Xinfang Wang, Qing Lv, Lin He, Jing Wang, Ling Li, Jing Zhang, Yi Wang, Jinfeng Liu, Yali Yang
Journal: Journal of the American College of Cardiology (2015)
Efficacy and safety of PF-00299804 (PF299), an oral, irreversible, pan-human epidermal growth factor receptor (pan-HER) tyrosine kinase inhibitor (TKI), as first-line treatment (tx) of selected patients (pts) with advanced (adv) non-small cell lung cancer (NSCLC).
Authors: T. Mok, D. R. Spigel, K. Park, M. A. Socinski, S. Y. Tung, D. Kim, G. Borzillo, H. Zhang, J. P. O'Connell, P. A. Janne
Journal: Journal of Clinical Oncology (2010)

7537 Background: Efficacy of gefitinib as first-line tx of adv NSCLC with epidermal growth factor receptor (EGFR) mutation (mu) has been shown in a phase (P) 3 trial. PF299 shows preclinical activity in EGFR-mutant NSCLC, including T790M (a secondary resistance mu arising in ∼50% of pts after EGFR TKI benefit). This open-label, single-stage P2 study evaluates efficacy and safety of first-line PF299 in a pt population with adv NSCLC, molecularly selected or clinically enriched for EGFR mu. Methods: Pts with adv adenocarcinoma of lung and no prior systemic tx for adv NSCLC are eligible if they are non/light smokers or known to have EGFR mu. Tissue is requested from all pts. Pts receive PF299 45 mg continuously once daily and are assessed every 28 days. Endpoints include: progression-free survival at 4 months (PFS4m; primary), tumor response, safety, serial pharmacokinetics, and tissue- and blood-based biomarkers, including T790M mu. Planned enrolment is ∼80 pts, including ≥ 30 each of Asian and of non-Asian ethnicity. Results: To date, 39 pts have enrolled (23 female; 23 Asian). Of 29 evaluable pts, 1 had a complete response, 6 a partial response, and 16 stable disease ≥ 6 weeks. Preliminary PFS rates at 3, 4, and 6 m were 90%, 79%, and 79%, respectively. Mu status was obtained in 31/39 pts. All evaluable pts with known EGFR mutant NSCLC (n = 14) showed tumor shrinkage. Common tx-related adverse event (AEs) were diarrhea (79%; grade 3; 9%), dermatitis acneiform (49%; 9%), stomatitis (42%; 6%), acne (24%; 0%), rash (21%; 0%), and anorexia (18%; 0%). One pt discontinued due to AE; 10 required dose reduction while remaining on study. Conclusions: Preliminary data suggest PF299 demonstrates encouraging efficacy as first-line tx of selected Asian and non-Asian pts with NSCLC, as reflected by PFS rates. Of note, tumor shrinkage was seen in all evaluable pts with EGFR mutant disease. AEs were mostly grade 1/2 and manageable; however, to ensure long term tolerability, a lower starting dose is being considered. Clinical follow-up and biomarker data will be presented. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer AstraZeneca, AVEO, Boehringer Ingelheim, Eisai, Genentech, Lilly, Merck Serono, OSI Pharmaceuticals, Pfizer, Roche, Syndax Pharmaceuticals Gatekeeper Pharmaceuticals, Pfizer AstraZeneca, Genentech, Lilly, Pfizer, Roche, sanofi-aventis Abraxis BioScience, Celgene, Genentech, Lilly, Pfizer Genzyme
Safety and Tolerability of Intrathecal Liposomal Cytarabine during CNS Prophylaxis in Patients with Non Hodgkin Lymphoma and Acute Lymphoblastic Leukemia.
Authors: Luciana Annino, Barbara Anaclerico, Giulia Benevolo, Nicola Cascavilla, Michele Cimminiello, Matteo Dell’Olio, Alfredo Gagliardi, Giulio Giordano, Eustachio Miraglia, Maurizio Musso, Guido Parvis, Silvia Piano, Chiara Pilatrino, Renato Scalone, Adriano Venditti, Daniela Venditti, Umberto Vitolo, Sergio Storti
Journal: Blood (2007)
A cross-section questionnaire to evaluate patients’ satisfaction with totally implanted access ports (Port-a-Cath; PAC) and analysis of PAC-related complications at a tertiary care center.
Authors: Christoph Minichsdorfer, Thorsten Fuereder, Anna Sophie Berghoff, Gabriel Marta, Bruno Maehr, Michael Gnant, Christoph Zielinski, Rupert Bartsch
Journal: Journal of Clinical Oncology (2013)

e20693 Background: PACs are used for the administration of intravenous drugs. These devices have therefore become valuable tools for the application of chemotherapy in cancer patients (pts). Methods: During the period from 11.2012 to 01.2013, pts were invited to answer a simple questionnaire concerning quality-of-life and satisfaction with their respective PAC. Retrospective data regarding to PAC-related complications were collected by searching patient’s medical history. PAC-related thrombosis were defined as non-compressibility of the axillary or subclavian vein on ultrasound; PAC-related infections were defined as documented bacteraemia with a positive blood culture taken from the device in the absence of positive peripheral blood cultures. Results: A total number of 116 pts were included. Mean time since PAC implantation was 16.9 months. Complications during implantations occurred in 8 pts (6.9%), with bleeding and haematoma being the most frequently observed events; three patients experienced postsurgical pneumothorax (2.6%). Complications arising after PAC implantation consisted of infections (9 pts; 7.7%), drug extravasation (8 pts; 6.9%), PAC malposition (3 pts; 2.6%), and thrombosis (1 pt; 0.8%). PAC infections were caused most commonly by Pseudomonas aeroginosa (3 cases). One quarter of all pts reported that their PAC interfered activities of daily life. In 15 cases (13%) the PAC caused pain, especially when moving the arm (11 pts; 9.5%); only 6% reported that PAC punctuations were more painful than accessing a peripheral vein. 98 pts (84%) agreed that the PAC alleviates the administration of therapy. Indeed, the vast majority (84%) would once again choose a PAC for chemotherapy administration. Conclusions: PACs are valuable tools to ease the burden of chemotherapy administration. Most patients were satisfied, as PACs provide a relatively easy and safe way of venous access. Nevertheless, implantation and maintenance of these systems carry potential risks.
Total Body Irradiation 1350cGy/Fludarabine (TBI/FLU) vs Myeloablative Busulfan/Fludarabine (Bu/Flu) Preparation in Adult Recipients of Dual Umbilical Cord Blood (UCB) Transplantation: Superior Engraftment with Low Treatment-Related Mortality
Authors: Mitchell Horwitz, John Chute, Cristina Gasparetto, Gwynn Long, David Rizzieri, Keith Sullivan, Jackie McPherson, Nelson Chao
Journal: Blood (2008)
PITX2 Modulates Atrial Membrane Potential and the Antiarrhythmic Effects of Sodium-Channel Blockers
Authors: Fahima Syeda, Andrew P. Holmes, Ting Y. Yu, Samantha Tull, Stefan Michael Kuhlmann, Davor Pavlovic, Daniel Betney, Genna Riley, Jan P. Kucera, Florian Jousset, Joris R. de Groot, Stephan Rohr, Nigel A. Brown, Larissa Fabritz, Paulus Kirchhof
Journal: Journal of the American College of Cardiology (2016)

Antiarrhythmic drugs are widely used to treat patients with atrial fibrillation (AF), but the mechanisms conveying their variable effectiveness are not known. Recent data suggested that paired like homeodomain-2 transcription factor (PITX2) might play an important role in regulating gene expression and electrical function of the adult left atrium (LA). After determining LA PITX2 expression in AF patients requiring rhythm control therapy, the authors assessed the effects of Pitx2c on LA electrophysiology and the effect of antiarrhythmic drugs. LA PITX2 messenger ribonucleic acid (mRNA) levels were measured in 95 patients undergoing thoracoscopic AF ablation. The effects of flecainide, a sodium (Na+)-channel blocker, and d,l-sotalol, a potassium channel blocker, were studied in littermate mice with normal and reduced Pitx2c mRNA by electrophysiological study, optical mapping, and patch clamp studies. PITX2-dependent mechanisms of antiarrhythmic drug action were studied in human embryonic kidney (HEK) cells expressing human Na channels and by modeling human action potentials. Flecainide 1 μmol/l was more effective in suppressing atrial arrhythmias in atria with reduced Pitx2c mRNA levels (Pitx2c+/–). Resting membrane potential was more depolarized in Pitx2c+/– atria, and TWIK-related acid-sensitive K+ channel 2 (TASK-2) gene and protein expression were decreased. This resulted in enhanced post-repolarization refractoriness and more effective Na-channel inhibition. Defined holding potentials eliminated differences in flecainide's effects between wild-type and Pitx2c+/– atrial cardiomyocytes. More positive holding potentials replicated the increased effectiveness of flecainide in blocking human Nav1.5 channels in HEK293 cells. Computer modeling reproduced an enhanced effectiveness of Na-channel block when resting membrane potential was slightly depolarized. PITX2 mRNA modulates atrial resting membrane potential and thereby alters the effectiveness of Na-channel blockers. PITX2 and ion channels regulating the resting membrane potential may provide novel targets for antiarrhythmic drug development and companion therapeutics in AF.
A phase II study of tivozanib in patients with metastatic and nonresectable soft-tissue sarcomas
Authors: M. Agulnik, R.L.B. Costa, M. Milhem, A.W. Rademaker, B.C. Prunder, D. Daniels, B.T. Rhodes, C. Humphreys, S. Abbinanti, L. Nye, R. Cehic, A. Polish, C. Vintilescu, T. McFarland, K. Skubitz, S. Robinson, S. Okuno, B.A. Van Tine
Journal: Annals of Oncology (2016)
Spatio-temporal mutation profiles of case-matched colorectal carcinomas and their metastases reveal unique de novo mutations in metachronous lung metastases by targeted next generation sequencing
Authors: Valentina Kovaleva, Anna-Lena Geissler, Lisa Lutz, Ralph Fritsch, Frank Makowiec, Sebastian Wiesemann, Ulrich T. Hopt, Bernward Passlick, Martin Werner, Silke Lassmann
Journal: Molecular Cancer (2016)

Targeted next generation sequencing (tNGS) has become part of molecular pathology diagnostics for determining RAS mutation status in colorectal cancer (CRC) patients as predictive tool for decision on EGFR-targeted therapy. Here, we investigated mutation profiles of case-matched tissue specimens throughout the disease course of CRC, to further specify RAS-status dynamics and to identify de novo mutations associated with distant metastases. Case-matched formalin-fixed and paraffin-embedded (FFPE) resection specimens (n = 70; primary tumours, synchronous and/or metachronous liver and/or lung metastases) of 14 CRC cases were subjected to microdissection of normal colonic epithelial, primary and metastatic tumour cells, their DNA extraction and an adapted library protocol for limited DNA using the 48 gene TruSeq Amplicon Cancer PanelTM, MiSeq sequencing and data analyses (Illumina). By tNGS primary tumours were RAS wildtype in 5/14 and mutated in 9/14 (8/9 KRAS exon 2; 1/9 NRAS Exon 3) of cases. RAS mutation status was maintained in case-matched metastases throughout the disease course, albeit with altered allele frequencies. Case-matched analyses further identified a maximum of three sequence variants (mainly in APC, KRAS, NRAS, TP53) shared by all tumour specimens throughout the disease course per individual case. In addition, further case-matched de novo mutations were detected in synchronous and/or metachronous liver and/or lung metastases (e.g. in APC, ATM, FBXW7, FGFR3, GNAQ, KIT, PIK3CA, PTEN, SMAD4, SMO, STK11, TP53, VHL). Moreover, several de novo mutations were more frequent in synchronous (e.g. ATM, KIT, PIK3CA, SMAD4) or metachronous (e.g. FBXW7, SMO, STK11) lung metastases. Finally, some de novo mutations occurred only in metachronous lung metastases (CDKN2A, FGFR2, GNAS, JAK3, SRC). Together, this study employs an adapted FFPE-based tNGS approach to confirm conservation of RAS mutation status in primary and metastatic tissue specimens of CRC patients. Moreover, it identifies genes preferentially mutated de novo in late disease stages of metachronous CRC lung metastases, several of which might be actionable by targeted therapies.
An Observation On Clinical Outcomes of HLA-Haplotype Hematopoietic Stem Cell Transplantation with High-Dose and Post-Transplantation Cyclophosphamide for Children Malignancies Hematopathy
Authors: Chunfu Li, Yuelin He, Xuedong Wu, Zhiyong Peng, Xiaoqin Feng, Qifa Liu
Journal: Blood (2012)
Upregulation of KLF4 Expression in Pediatric B-NHL Lymphomas and Its Association with Low EFS and Poor Survival Following Treatment with Chemotherapy
Authors: Mario I Vega, Miriam Hernandez-Atenogenes, Alberto Valencia, Gabriel G Vega, Altagracia Maldonado-Valenzuela, Guillermo Ramon, Haiming Chen, James R. Berenson, Otoniel Martinez-Maza, Hector Mayani, Sara Huerta-Yepez, Benjamin Bonavida
Journal: Blood (2011)
Phase II study of danusertib (D) in advanced/metastatic non-small cell lung cancers (NSCLC).
Authors: Thomas Christoph Gauler, Benjamin Besse, Silvia Novello, Egbert F. Smit, Elizabeth R. Plummer, Jean-Pierre Delord, Maurizio Nicodemo, Armando Santoro, Carlo Barone, Paolo Marchetti, Pier Franco Conte, Maja J. De Jonge, Ahmad Awada, Mariangela Mariani, Maria Gabriella Jannuzzo, Anna Petroccione, Roberta Ceruti, Cristina Davite, Wilfried Ernst Erich Eberhardt
Journal: Journal of Clinical Oncology (2013)

e19138 Background: D is an ATP competitive pan-aurora kinases inhibitor with activity also against FGFRs, VEGFR, Ret, TrkA, Scr, and Abl. Methods: Eligible pts had NSCLC progressing for advanced/metastatic disease after 1 prior chemotherapy line (CT). Primary endpoint was progression-free survival at 4 months (PFS-4) evaluated in a Simon two-stage design. Number of successes required for not rejecting the alternative hypothesis (40% PFS-4) was ≥4/19 evaluable pts while the number of successes required to reject at the end of stage 2 the null hypothesis (20% PFS-4) was ≥11/36 (α 1-sided = 0.1). D was administered at 500 mg/m² as 24 hr IV infusion q2w. The expression of Aurora A/B, TPX-2, MDR, Scr, Survivin by IHC and the amplification of FGFR1 by FISH on tumor biopsies of consenting pts were evaluated. Results: 3 out of 19 evaluable pts were PFS-4 at the end of the 1 st stage, thus precluding passage to the 2 nd stage. Interestingly, in pts with squamous (SCC) (n=7), median PFS and OS were 6.4 and 10.6 mos respectively (vs. 2.2 and 7.6 mos, in non-SCC pts), suggesting a possible specific effect in this subtype. Additional pts with SCC were therefore treated under a protocol amendment. At the end of this 2 nd stage, 5/31 evaluable SCC pts (80% CI: 0.08-0.28) were PFS-4 indicating that the predefined threshold required to conclude for activity would not have been reached. Overall 56 pts, all histology NSCLC, were treated: median age 62 yrs (39-79), 64% male, 70% SCC, 36% with &gt;1 prior CT. Best response was a PR in 1 pt and SD in 20 pts; median PFS and OS were 2.1 and 8.3 mos respectively. The most frequent drug-related AEs (any Grade, ≥20%) were: uncomplicated and short lasting neutropenia (94%), nausea (39%), fatigue (37%), asthenia (30%), anorexia and diarrhea (29%), alopecia (23%). Histological analyses by IHC and FISH is still ongoing: results will be presented. Conclusions: Limited evidence of activity was observed, insufficient to meet the predefined threshold to call efficacy in NSCLC when D was administered as monotherapy at this dose/schedule. D confirmed to have a manageable safety profile. Clinical trial information: 2006-003772-35.
Abstract A26: The RON tyrosine kinase accelerates pancreatic duct neoplasia and activates a positive autocrine/paracrine signaling loop that promotes alternative macrophage activation
Authors: Michele L. Babicky, Megan M. Harper, Evangeline S. Mose, Dawn J. Jaquish, Randall P. French, Susan E. Waltz
Journal: Cancer Research (2016)

Abstract Introduction: The RON (receptor d'origine nantais) tyrosine kinase is overexpressed in &amp;gt;80% of human pancreatic cancers, but its effect on pancreatic carcinogenesis is largely unknown. Methods: We developed a transgenic mouse that overexpresses RON specifically in the pancreas (Pdx-1-RON). Additionally, we utilized an existing transgenic mouse with a functionally inactive RON tyrosine kinase domain (Pdx-1-RTK-/-). These strains were crossed with the established CK murine model of pancreatic cancer yielding compound strains, RCK and CK/TK-/-. We performed immunofluorescent staining, flow cytometry, and western blot analysis on the tissues from these animals to study the effects of RON overexpression and the loss of RON signaling in the setting of oncogenic Kras. Results: RON overexpression results in increased acinar-ductal metaplasia, accelerates PanIN progression to invasive cancer, and results in an accumulation of alternatively-activated (MRC1+) macrophages in the tumor microenvironment. We found that RON overexpression results in upregulation of its own ligand, macrophage-stimulating protein (MSP), activating a positive autocrine/paracrine signaling loop that effects tumor growth and the differentiation of tumor-associated macrophages. Knockdown of RON expression and/or MSP expression results in decreased tumor growth in vivo. Additionally, loss of RON signaling in CK/TK-/- mice leads to a profound decrease in alternatively-activated (MRC1+) macrophages in the tumor microenvironment. In contrast, these animals demonstrate an accumulation of classically activated (CD11c+) macrophages. RON signaling is also associated with downregulation of the chemokine, monocyte chemoattractant protein-1 (MCP-1), a known driver of CD11c+ macrophage activation. The correlation of RON and MSP and the inverse correlation with MCP-1 expression were validated in a database analysis of human pancreatic tumor specimens. Conclusion: Our studies demonstrate that murine RON overexpression accelerates the development of invasive pancreatic cancer in the setting of oncogenic Kras. Active RON signaling results in upregulation of its own ligand, MSP, initiating a positive autocrine/paracrine feedback loop that promotes tumor growth and alters the differentiation of macrophages in the tumor microenvironment. Citation Format: Michele L. Babicky, Megan M. Harper, Evangeline S. Mose, Dawn J. Jaquish, Randall P. French, Susan E. Waltz. The RON tyrosine kinase accelerates pancreatic duct neoplasia and activates a positive autocrine/paracrine signaling loop that promotes alternative macrophage activation. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr A26.