tbuckley/cabot-search huggingface dataset:
The risk for brain metastases in HER2 3+ BC five years after primary BC diagnosis.
Authors: Z. Tomasevic, Z. Kovac, Z. Milovanovic, D. Gavrilovic
Journal: Journal of Clinical Oncology (2011)

e11091 Background: More than 30% of HER2 3+ BC develops brain metastases (BM) eventually, usually in the first 2-3 years after BC diagnosis. Risk for distant metastases in HER2 3+ BC remains for many years, but there are no data regarding the long term risk for BM The aim of this analysis is to is to explore whether risk for late BM, defined as BM relapse after 5 years of diagnosis) differs between patients with HER2 3+ and HER2- BC. Methods: Between January 2007-January 2011, 133 consecutive BC BM pts were identified. Patients were evaluated for age, ER/PGR/HER2 status, time to BM and BM as first relapse site according to HER2 status. BM as a first relapse site also includes BM diagnosed within 2 months after metastases in other organs developed. Results: Median age was 49 years (range 25-79); HER2 status (HercepTest, Dako) was known for 118 pts (88.7%) and they are considered for this analysis. HER 2 3+ was confirmed in 40 (34 %), HER2 0-2+ (2+ confirmed by CISH) in 78 (66%) and triple negative status in 19 (16 %) pts. Median time to BM in HER2 negative pts was 36 months (range 0-252).Median time to BM in HER2 3+ BC was 25 months (range 0-96); 39/40 (97,5%) HER2 3+ pts developed BM within 0-60 months, and only 1 MBC pt developed BM 96 months after BC diagnosis. That unique MBC patient, treated with trastuzumab for 8 years developed infra-tentorial BM as a terminal event. Conclusions: There is a striking difference in late BM development between HER2 3+ and HER2 negative BC. For some reason, HER2 3+ BC does not or extremely rarely metastasize to the brain 5 yrs after BC diagnosis, even if metastases in the other organ sites are present. It seems that if HER2 3+ pt survive > 5 yrs without metastases, BM development is highly unlikely. Risk for BM in HER2 negative pts is retained for many years (up to 21 yrs), even as a first relapse site. These results could be important for potential future prophylactic BM strategies. BM HER2 0-2+ (66%) HER2 3+ (34%) P Median time (months) 36 (0-252) 25 (0-96) p<0.01 Late development >60 months (%) 23/78 (29,5%) 1/39 (2.5%) p<0.01 First relapse site (%) 56/78 (71%) 16/40 (40%) p<0.01
Comparison of elapsed times from breast cancer detection to first adjuvant therapy in a Canadian province, 1999–2000 and 2003–2004
Authors: D. Rayson, J. Meadows, T. Younis, R. Dewar
Journal: Journal of Clinical Oncology (2005)

6005 Background: Wait times for cancer treatment are of significant concern to the Canadian public. Previous studies of time to breast cancer care have examined single care events such as time to surgery. The spectrum of care however extends from disease detection to completion of adjuvant therapies. Our objective was to compare elapsed times from breast cancer detection to start of first adjuvant therapy in a Canadian province over 2 time periods; 1999–2000 and 2003–2004. Methods: A retrospective chart review was performed. All eligible women had pathologic confirmation of invasive disease and were referred to a provincial cancer center between Sept 1, 1999-Sept 1, 2000 (cohort 1) and Sept 1, 2003-Sept 1, 2004 (cohort 2). All dates were abstracted from patient charts and electronic records. The log-rank test was used to assess differences in time to events between cohorts. Results: Care intervals assessed (cohort 1 vs 2, median days); (I) detection to pathologic confirmation; 13d vs 14d (p=.12) (II) pathologic confirmation to definitive surgery; 21d vs 24d (p=.002) (III) definitive surgery to referral receipt at cancer center; 16d vs 19d (p=.005) (IV) referral receipt to patient contact; 10.5d vs 6d (p=.04) (V) patient contact to first med/rad onc appt; 5d vs 6d (p=.48) (VI) first appt to start of first adjuvant therapy 11d vs 18.5d (p=.03). Summary elapsed times are presented below with interquartile ranges (IQR). Conclusions: The majority of women experience long elapsed times for breast cancer care. Elapsed times have lengthened over the cohorts studied, although the overall difference did not reach statistical significance. Intervals prior to referral receipt at cancer centers account for prolongation in elapsed times between cohorts. Our data, spanning a sequence of care events, more fully elucidates waiting time burden and may provide a framework for the design and evaluation of programs aimed at reducing elapsed care times. No significant financial relationships to disclose.
A phase II trial of pralatrexate (P) plus oxaliplatin (O) in advanced esophagogastric cancer (aEGC).
Authors: Usha Malhotra, Austin Miller, Peter Walter Bushunow, Peter Loud, Araba Adjei, Saikrishna S. Yendamuri, Melissa Robins, Renuka V. Iyer, Nikhil I. Khushalani
Journal: Journal of Clinical Oncology (2015)

152 Background: Advanced EGC is an aggressive cancer with limited treatment (Rx) options. In preclinical studies P has demonstrated increased cellular uptake and polyglutamylation relative to other anti-folates plus is synergistic with platinum. We evaluated combination P plus O in aEGC and examined pharmacogenomics and tumor microRNA profiling to identify predictive signatures for response and toxicity. Here we report on clinical outcome data for the entire cohort. Methods: Objective response (OR) following P+O was assessed in an exact 2-stage design, including early stopping for futility and a safety lead-in cohort of 6 patients (pts) with provisions for dose de-escalation for dose limiting toxicity (DLT). Eligibility included metastatic/unresectable, therapy-naïve EGC pts with adequate organ and functional status and &lt; G2 neuropathy. Rx consisted of biweekly O (85mg/m2) plus P (Dose level [D] 1, 120mg/m2; dose level -1 [D-1] 100 mg/m2). O was stopped after 12 cycles. Secondary endpoints were toxicity, survival and molecular correlates. Results: The study met its interim efficacy threshold and proceeded to full accrual. 35 pts, median age 67 yrs (39-83), 32 males, mostly adenocarcinoma (29) were accrued. 2/4 pts at D1 developed DLTs (1 G3 diarrhea, 1 G3 mucositis). All remaining pts were treated at D-1, which had no DLTs in the safety cohort. G4 toxicity included neutropenia (2) and myocardial infarction (1). The most common G3 events were mucositis (5), dehydration and neutropenia (4 each), anorexia, neuropathy, fatigue and nausea/vomiting (all 3 each). Including G1 and 2 events, myelosuppression, mucositis and neuropathy were the most common toxicities. Median # of P cycles administered at D-1 was 8 (1, 17). In an intent to treat analysis, confirmed OR was 23% (8/35) and 16 pts (46%) had stable disease. 3 pts were non-evaluable for response. Conclusions: Combination O and P administered biweekly at 85mg/m2 and 100 mg/m2 respectively is safe, well-tolerated and has modest efficacy in aEGC. Survival analysis results will be available for the meeting. This study was approved and funded by the NCCN from general research support provided by Allos Therapeutics, a subsidiary of Spectrum Pharmaceuticals, Inc. Clinical trial information: NCT01178944.
The impact of infliximab therapy on intestinal mucosal expression of matrix metalloproteinase and ADAM genes in patients with inflammatory bowel disease.
Authors: I. Arijs, K. Lemaire, R. Quintens, L. Van Lommel, C. Perrier, Kristel Van Steen, G. De Hertogh, G. Van Assche, S. Vermeire, K. Geboes, F. Schuit, P. Rutgeerts
Journal: Gut (2009)
Randomized comparison of adjuvant tamoxifen (Tam) versus no hormonal treatment for premenopausal women with node-positive (N+), early stage breast cancer: first results of International Breast Cancer Study Group Trial 13–93
Authors: M. Colleoni, S. Gelber, R. Snyder, S. B. Holmberg, M. Fey, B. Thuerlimann, J. Lindtner, M. Byrne, C. Mendiola, A. S. Coates
Journal: Journal of Clinical Oncology (2004)

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Transfemoral Tricuspid Valve Repair Using a Percutaneous Mitral Valve Repair System
Authors: Joachim Schofer, Claudia Tiburtius, Christoph Hammerstingl, Per-Olof Dickhaut, Julian Witt, Lorenz Hansen, Friedrich-Christian Riess, Klaudija Bijuklic
Journal: Journal of the American College of Cardiology (2016)
Abstract P424: Determinants of Objectively Measured Physical Activity in Patients Entering a Phase III Cardiac Rehabilitation Program
Authors: Wonwoo Byun, Cemal Ozemek, Katrina Riggin, Scott Strath, Leonard Kaminsky
Journal: Circulation (2013)

Introduction: Despite well-known benefits of physical activity (PA) on long-term health in cardiac patients, many cardiac patients remain inactive. In order to develop effective interventions to pr...
A case of hypereosinophilic syndrome is associated with the expansion of a CD3-CD4+ T-cell population able to secrete large amounts of interleukin-5
Authors: D Brugnoni, P Airo, G Rossi, A Bettinardi, HU Simon, L Garza, C Tosoni, R Cattaneo, K Blaser, A Tucci
Journal: Blood (1996)
Phase II study of exemestane (E) in refractory ovarian cancer (ROC)
Authors: S. Verma, M. Alhayki, T. Le, K. Baines, L. Rambout, L. Hopkins, M. Fung Kee Fung
Journal: Journal of Clinical Oncology (2006)

5026 Background: Despite biologic rationale, endocrine therapeutic strategies have been under investigated in ovarian cancer. This is the first study to report the efficacy of an aromatase inhibitor, E, in patients (pts) with ROC. Methods: This was a pilot, phase II, single-centre, non-comparative, open-label study. Pts with ROC stage II - IV who had received no more than 2 lines of prior chemotherapy, had ECOG PS ≤ 2, and measurable disease or non-measurable disease with a CA 125 ≥ 30 U/mL and/or ascites were eligible. All pts must have received prior platinum and taxane chemotherapy. Treatment consisted of E 25mg p.o. daily until disease progression. The primary endpoint was objective response rate (ORR) and secondary endpoints were time to progression (TTP), duration of response (DR) and toxicity. Results: 24 pts have been enrolled to date. Only 2 pts who withdrew consent or never started E were excluded from this analysis. Subjects had stage III (77%) or IV (18%) ovarian cancer, the majority were grade 3,serous histology. 15 pts (68%) had 2 prior lines of therapy and 7 pts (32%) had only 1 prior line of therapy. Treatment was commenced in the majority immediately after progression on chemotherapy. There were no objective clinical responses; however 8/22 (36%) pts had stable disease (SD) &gt;14 weeks (med. duration 23 wks). One pt remains with SD &gt; 95 wks duration. The median TTP was 8.8 wks. Receptor status was available in 16/22 pts: ER+ (41%), PgR+ (32%), BCL-2+ (23%) and HER2+ (0%). Correlation of ORR/SD with receptors and CA 125 will be presented. Toxicity was evaluated in all pts who received at least one dose of E. Hyponatremia (gr 4), attributed to disease, was observed in 1 pt. All other toxicities were NCI CTC grade ≤ 2: fatigue (14%), hot flashes (9%), skin reaction (5%), and fluid retention (5%). Conclusions: In this highly refractory ROC pt population, E was associated with an impressive, clinically meaningful SD rate of 36%. As this potentially represents a less toxic, well-tolerated therapeutic option for women with ROC, further investigation is warranted. Supported by a grant from Pfizer Canada No significant financial relationships to disclose.
Abstract 12979: Increase in Exogenous Lipoproteins Characterized by Apolipoprotein B48 and Cholesterol Absorption/Synthesis Markers Represents Residual Risks for Coronary Artery Disease during Intensive LDL-Lowering Therapy
Authors: Kenta Mori, Tatsuro Ishida, Tomoko Monguchi, Maki Sasaki, Kensuke Kondo, Minoru Hasokawa, Hideto Nakajima, Yoko Haraguchi, Li Sun, Tomoyuki Yasuda, Ryuji Toh, Ken-ichi Hirata
Journal: Circulation (2012)
Cellular immune parameters associated with improved long-term survival in advanced stage breast cancer patients after active immunization with a HER2-specific vaccine
Authors: M. L. Disis, J. H. Strickler, D. Wallace, V. Goodell, L. G. Salazar, D. Higgins, J. Childs, K. Tietje, Y. Dang, M. Slota
Journal: Journal of Clinical Oncology (2008)

3015 Background: Clinical trials of HER2 vaccines have demonstrated that breast cancer patients can be immunized against HER2 and HER2-specific T cells persist long after vaccination. Immunization with HER2 vaccines is associated with the development of epitope spreading; a broadening of immunity to epitopes throughout the HER2 protein. We evaluated the clinical impact of vaccine induced HER2 specific cellular immunity in breast cancer patients immunized with HER2 vaccines. Methods: 75 subjects from 3 phase I-II vaccine trials were analyzed. T cell responses to HER2 peptides, intracellular (ICD) protein and tetanus toxoid (TT) were assessed by tritiated thymadine incorporation. Subjects were included in the analysis if they had complete baseline labs and received at least three vaccinations. Any SI >2.0 was considered positive. Epitope spreading was defined as a positive post-vaccination response to a non-vaccinating peptide. In addition, the relationship between T cell response and overall survival (OS) was assessed (n=50). Patients were followed a median of 2.7 years. Results: There was a significant difference in level of HER2 ICD immunity after vaccination between stages. There were also significant differences in peptide specific SI (p=0.034) and presence of epitope spreading (p=0.006) between stages. HER2 peptide-specific SI was a significant predictor of epitope spreading (p=0.031). Subjects with epitope spreading had significantly higher peptide responses (mean SI: 11.5) than subjects without epitope spreading (mean SI: 3.3) (p<0.001). Univariate analysis demonstrated patients with epitope spreading had longer OS than patients without epitope spreading (p=0.029, HR=0.50), and increased HER2, but not TT, specific T cell immunity, was associated with improved survival (p=0.025, HR=0.94). Multivariate analysis indicated that HER2, but not TT, specific T cell immunity, was an independent variable (p=0.021, HR=0.86) for prediction of OS in advanced stage subjects. Conclusions: These data suggest that vaccine-induced HER2 specific cellular immune response, with epitope spreading, may have clinical benefit and should be further evaluated in the context of phase II studies. No significant financial relationships to disclose.
A phase I study to evaluate safety, immunogenicity and anti-tumor activity of the multi-peptide vaccine IMA901 in renal cell carcinoma patients (RCC)
Authors: M. Staehler, A. Stenzl, P. Y. Dietrich, T. Eisen, A. Haferkamp, J. Beck, A. Mayer, S. Walter, H. Singh-Jasuja, C. Stief
Journal: Journal of Clinical Oncology (2007)

5098 Background: IMA901 is a therapeutic cancer vaccine based on multiple synthetic tumor-associated peptides confirmed to be naturally presented by analysis of primary RCC tissues. IMA901 consists of 9 HLA-class I-binding and 1 HLA class II-binding peptides with the capacity to activate cytotoxic T cells (CD8+ T cells) and T helper cells (CD4+ T cells). Methods: 30 patients with stage III/IV RCC were enrolled in a single arm, multi-centre study. The endpoints were safety, T-cell responses, pharmacokinetics of the intradermal application of GM-CSF and anti-tumor activity according to RECIST. Patients had to be HLA-A*02 positive and received 8 intradermal vaccinations on days 1, 2, 3, 8, 15, 22, 36 and 64 each consisting of 4.5 mg IMA901 and 75 μg GM-CSF. Results: The most prevalent adverse events (AEs) were fatigue, cough and headache. Aseptical lymphadenitis and injection site reactions such as erythema, edema and pruritus were the most frequent possibly drug-related AEs. All possibly drug-related adverse events were mild to moderate. No patient experienced any possibly drug-related serious adverse events or deaths during the study. Pharmacokinetic data provided no evidence for accumulation of GM-CSF upon repeated i.d. administration. 74% of patients showed a vaccine-induced specific T-cell response and 30% of patients responded to multiple peptides contained in IMA901. The overall tumor assessment in patients with measurable disease revealed that 8 patients (35%) demonstrated a clinical benefit (1 PR + 7 SD). Most encouraging, patients who elicited multiple T-cell responses showed a statistically significant higher clinical benefit rate. Conclusions: IMA901 is safe, very well tolerated and immunogenic. Clinically observed tumor growth control in RCC patients may imply anti-tumor activity strongly supported by two patients with tumor regression (1 PR and 1 patient with 27% shrinkage in target lesions). The mode of action is strongly supported by the finding that multiple T-cell responders were significantly more likely to have a clinical benefit. These data clearly support the further development of IMA901. No significant financial relationships to disclose.
Reduced vehicle-related side effects of paclitaxel combined with gemcitabine for stage IIIB or IV non-small cell lung cancer: A phase II trial result
Authors: N.-M. Chu, C. Hsieh, W. Fang, S. Chang, Z. Chu
Journal: Journal of Clinical Oncology (2004)

7260 Background: A formulation-modified paclitaxel (Genetaxyl) was shown to be active and safe as a monotherapy in a previous phase II trial of advanced breast cancer. Since Genetaxyl is formulated in 60% less of Cremophor EL (CrEL) compared with traditional paclitaxel, it's important to find out the overall effectiveness of Genetaxyl co-administered with other cytotoxic drugs for cancer patients. Paclitaxel combined with gemcitabine for non-small cell lung cancer (NSCLC) seems a reasonable choice because both agents have shown activity with almost non-overlapping toxicity for NSCLC. Besides, lung cancer is the leading cause of cancer death in Taiwan. Methods: It was an open-label phase II trial. Genetaxyl 175 mg/m2 administered intravenously over 3 hours followed by 30 minutes infusion of gemcitabine 1000 mg/m2 on day 1 and gemcitabine 1000 mg/m2 alone on day 8 every 21 days as one cycle was given to patients for 2–6 cycles. Efficacy response was evaluated every 2 cycles using RECIST (response evaluation criteria in solid tumor), and safety was recorded using WHO criteria. Results: From June 2001 to February 2003, 28 patients with stage IIIB (7) or stage IV (21) NSCLC were recruited. For efficacy, 27 out of 28 patients were evaluable. Overall response rate was 48.1% with no CR. Twelve (44%) patients had SD and 2 (7.4%) had PD. One-year survival was 66.7%. Total of 144 cycles were given to 28 patients. Toxicities observed per-patient are listed in the table. Slow-onset and manageable skin rash without accompanied severe hypersensitivity was observed in 78.5% (22/28) of patients. Conclusions: Reducing the amount of CrEL in the formulation does not affect the overall activity of Genetaxyl combined with gemcitabine. The efficacy, survival, and safety results look promising to warrant further confirmatory study. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genovate Biotechnology, Inc. Genovate Biotechnology, Inc. Genovate Biotechnology, Inc.
Communication of Recurrence Risk Estimates to Patients Diagnosed With Breast Cancer
Authors: Brian J. Zikmund-Fisher, Nancy K. Janz, Sarah T. Hawley, Kent A. Griffith, Aaron Sabolch, Reshma Jagsi
Journal: JAMA Oncology (2016)

This survey of medical oncologists and surgeons examines how often they use informational tools and provide patients diagnosed as having breast cancer with detailed recurrence risk information, and explores what clinician characteristics influence these behaviors.
A novel natural product inhibitor for the PI3K pathway.
Authors: Nuria de Pedro, Bastien Cautain, Victor Gonzalez-Menendez, Gloria Crespo, Lorena Rodriguez, Caridad Diaz, Teresa Fernandez-Acero, Victor J. Cid, Maria Molina, Fernando Reyes, Francisca Vicente, Olga Genilloud
Journal: Journal of Clinical Oncology (2015)

e13523 Background: The phosphatidylinositol 3-kinase (PI3K) pathway couples receptor-mediated signaling to essential cellular functions by generating the lipid second messenger phosphatidylinositol-3,4,5-trisphosphate. This pathway is implicated in several cellular processes, critical for cancer progression. Inappropriate co-option of PI3K signaling is one of the most frequent occurrences in human cancer. Significant efforts have been made to generate inhibitors of the PI3K pathway to treat different cancers. New PI3K pathway inhibitors present both a great therapeutic opportunity and a tremendous challenge for cancer therapy due to at the differences in isoform/selective PI3K inhibitors depending on the the kind of cancer. Methods: High Throughput Screening (HTS) bioassay, using as a model Saccharomyces cerevisiae, that has reconstituted PI3K pathway was used. From 9600 extracts, 0.6% led to a recovery of yeast growth reproducibly, selectively, and in a dose-dependent manner. To follow the extracts activity, MCF-7 cell line was selected as a human model. CFSE assay in HCS permitted the identification to active fractions. With the active molecule, flow cytometry technique was used to determinate the effect on cell cycle. The mechanism of action (MOA) of the active molecule was evaluated by Western blot technique. Cytotoxicity and hERG inhibiton was measured using functional assays; LC-MS assays was used for cytochrome inhibition and stability. Results: This new natural product (MDN-0088) has a molecular weight 442,22 Da with IC50s 3.4µM in CFSE assay. The compound is an inhibitor of PI3K pathway, blocking the cell cycle in G0/G1 phase. The compounds displayed no significant toxicity (IC50 above 50 µM) against the HepG2 human hepatocyte cell line, presented the hERG potassium channel IC50s higher than 50 µM and exhibited also weak CYP450 inhibition with IC50 above 40 µM. Attending to the classification bands in metabolic stability, MDN-0088 can be classified as high clearance in human liver microsomes. Conclusions: We report herein the discovery of a novel natural product with activities against cancer as a PI3K inhibitor pathway. This discovery represents a new scaffold which may provide a starting point for the development of a novel treatment for cancer.
Lugol's Solution in Failing Lactation
Authors: D. P. Nicholson
Journal: BMJ (1948)

The minimum inhibiting concentration of penicillin for Bact. coli diminishes to about 50% of its original value when magnesium ions are present in the culture treated with penicillin.It is interesting to note that exactly the same type of results was obtained with a strain of Shigella dysenteriae.It would thus seem that magnesium ions have the interesting property of converting normally insensitive organisms to a state more closely resembling that of the sensitive pathogens, probably by altering their metabolic reaction pathways.It is thus obvious that there is need for further work to assess the actual significance of (1) the Gram reaction in its relation to sensitivity or otherwise of the respective pathogens to penicillin, and (2) the assump- tion (Haslett, 1947) that the ability to produce penicillinase may be tied up with the absence of magnesium ribonucleate from penicillin-resistant organisms.Work on these aspects is in progress.