tbuckley/cabot-search huggingface dataset:
Efficacy of imatinib mesylate in metastatic GIST to the brain
Authors: A. Khan
Journal: Journal of Clinical Oncology (2005)

9050 Background: Metastatic gastrointestinal stromal tumors (GIST) were up until recently untreatable due to resistance to conventional chemotherapy. The discovery of Imatinib at the turn of the century has brought some hope to patients with this malignancy. Case Report: A 58 years old male was diagnosed with a large (11x12cm) GIST arising from the small bowel. It was successfully resected with no evidence of distant metastases. Over the next 15 months he was conservatively followed. On a follow-up CT scan of the abdomen, a 3cm cystic lesion was noted in the liver. Disease progression was noted in the liver over the next 7 months. Treatment with Imatinib mesylate 400mg was iniatiated. Partial response was achieved and imatinib was stopped after 5 months. Unfortunately, one month later he presented in a delirious state. He was found to have mild left hemiparesis with mild left sided ataxia. MRI of the brain revealed multiple small non-enhancing but hyperintense lesions mainly in the right fronto-parietal region and left cerebellar hemisphere. Treatment with imatinib was re-started at 400mg a day. His delirious state cleared within the next 2 weeks. His neurological examination became essentially normal over the following 2 months. Repeat cranial MRI done 10 weeks later showed complete resolution of the hyperintense lesions. He never received any steroids or cranial radiation therapy. Conclusions: Novel targeted therapies like Imatinib offer an effective treatment option for patients with advanced GIST, a malignancy that has been highly resistant to chemotherapy. This patient and a similar case reported earlier do suggest that Imatinib can cross the blood-brain barrier, contrary to that suggested in a chronic myeloid leukemia mouse model where Imatinib had limited cerebral spinal fluid penetration. No significant financial relationships to disclose.
Abstract 16016: The Effects of Lorcaserin on C-reactive Protein in Overweight and Obese Patients: Data From Two Phase 3 Trials
Authors: Domenica Rubino, Randi Fain, Joanne Quan, Tianshu Ma, William Shanahan, William Soliman
Journal: Circulation (2013)

Background:  Lorcaserin, a selective 5-HT 2C  agonist, 10 mg twice daily (bid) was approved in the US in 2012 for chronic weight management as an adjunct to reduced calorie diet and increased physical activity. This analysis evaluated the effect of weight loss on high-sensitivity C-reactive protein (hsCRP) in obese and overweight patients (pts) from the two phase 3 pivotal trials in which it was measured.   Methods:  In BLOOM (3182 pts without diabetes with BMI 30-45 kg/m 2  or 27-45 kg/m 2  and ≥1 weight-related comorbid condition; NCT00395135) and BLOOM-DM (604 pts with BMI 27-45 kg/m 2  and type 2 diabetes; NCT00603291), pts were randomized to placebo (pbo) or lorcaserin (lor) for 52 weeks. All pts received diet and exercise counseling. In this post hoc analysis, CRP levels at week (wk) 52 were assessed for the pbo and lor 10 mg bid groups of the modified intent-to-treat/last observation carried forward (MITT/LOCF) population of each study with a baseline hsCRP >3 mg/L (BLOOM 54% >3 mg/L, 46% 3 mg/L, 47% 3 mg/L.   Results:  Baseline CRP levels were comparable except for the BLOOM-DM lor bid group, which was higher than for pbo. CRP levels for wk 52 non-responders (   Conclusions:  Weight loss was associated with decreased hsCRP in patients with CRP levels >3 mg/L at baseline. Lorcaserin-treated wk 52 responders in the BLOOM trial had significantly greater improvements in hsCRP than wk 52 responders who received pbo. In this exploratory analysis, ≥5% weight loss at wk 52 on lorcaserin is associated with improved hsCRP levels compared with pbo in overweight and obese subjects without diabetes.
Abstract 14999: Cardiac Resynchronization Therapy in Stage Four (Pre-Dialysis) Chronic Kidney Disease patients
Authors: Ulas Hoke, Joep Thijssen, Enno van der Velde, Lieselot van Erven, Martin J Schalij, Jeroen J Bax, Victoria Delgado, Nina Ajmone Marsan
Journal: Circulation (2012)
Estrogen suppression of 8-week treatment with exemestane combined with triptorelin versus triptorelin alone in healthy premenopausal women
Authors: M. G. Jannuzzo, E. Di Salle, R. Spinelli, N. Pirotta, G. Massimini, P. Buchan
Journal: Journal of Clinical Oncology (2004)

2041 Background: Gonadotrophin-releasing hormone agonists (Gn-RHa), such as triptorelin (T), reduce the ovarian estrogen production in premenopausal women, thus inducing a reversible postmenopausal status. Aromatase inhibitors, such as exemestane (EX), are effective in inhibiting the extraovarian estrogen production in postmenopausal women. Methods: We conducted a randomized, double-blind study evaluating the endocrinological effects of EX or placebo (P) given in combination with T in healthy premenopausal volunteers. EX (Aromasin 25 mg) or P were given orally, once daily, starting on Study Day 1, for 8 weeks in 14 subjects per arm. T pamoate (Trelstar Depot 3.75 mg) was given IM twice, 4 weeks apart, on Study Day 1 and 29. Blood was collected at several pre-planned intervals from Day 1 to 73. The primary objective was to demonstrate greater estradiol (E2) suppression in the T+EX group, determined from the E2 AUCday 36–57. Results: E2 levels below the “castration threshold” of 20 pg/mL, an index of the ovarian effect of T, were observed in 13 out of 14 subjects in both arms at the end of the first 4-week cycle (Day 29), and in all subjects at the end of the second cycle (Day 57). The E2 and estrone (E1) results over time in these 13 subjects/arm are reported in the Table. In addition, no influence was exerted by EX on T-mediated effects (initial flare and subsequent suppression) on LH and FSH. The exposure to T, evaluated in the second cycle, was not influenced by EX treatment. The tolerability observed in the two treatment arms was comparable. Conclusions: Greater estrogen suppression was observed in premenopausal subjects on T plus EX versus T plus P. The increase in pharmacological effectiveness caused by EX may result in enhanced clinical effectiveness in premenopausal advanced breast cancer patients treated with a Gn-RHa. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pharmacia Italia Pharmacia Italia
Tumour necrosis factor-α plays a significant role in the Aldara-induced skin inflammation in mice
Authors: H. Vinter, K. Kragballe, T. Steiniche, M. Gaestel, L. Iversen, C. Johansen
Journal: British Journal of Dermatology (2015)

Journal Article Tumour necrosis factor‐α plays a significant role in the Aldara‐induced skin inflammation in mice Get access H. Vinter, H. Vinter Department of Dermatology Aarhus University Hospital P. P. Oerumsgade 11 Building 15B DK‐8000 Aarhus C Denmark Correspondence Hanne Vinter. E‐mail: hannevinter@dadlnet.dk Search for other works by this author on: Oxford Academic Google Scholar K. Kragballe, K. Kragballe Department of Dermatology Aarhus University Hospital P. P. Oerumsgade 11 Building 15B DK‐8000 Aarhus C Denmark Search for other works by this author on: Oxford Academic Google Scholar T. Steiniche, T. Steiniche Department of Pathology Aarhus University HospitalTage Hansens Gade 2 DK‐8000 Aarhus C Denmark Search for other works by this author on: Oxford Academic Google Scholar M. Gaestel, M. Gaestel Institute of Biochemistry Hannover Medical University 30625 Hannover Germany Search for other works by this author on: Oxford Academic Google Scholar L. Iversen, L. Iversen Department of Dermatology Aarhus University Hospital P. P. Oerumsgade 11 Building 15B DK‐8000 Aarhus C Denmark Search for other works by this author on: Oxford Academic Google Scholar C. Johansen C. Johansen Department of Dermatology Aarhus University Hospital P. P. Oerumsgade 11 Building 15B DK‐8000 Aarhus C Denmark Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 174, Issue 5, 1 May 2016, Pages 1011–1021, https://doi.org/10.1111/bjd.14320 Published: 01 May 2016
Effect of Lectins on 3H-Uridine and 3H-Thymidine Uptake by Cultured Renal Cell Carcinoma and Normal Renal Cells
Authors: M.A. Bazeed, E. Becht, T. Schärfe, J. Schmidt, G.H. Jacobi, J.W. Thüroff
Journal: European Urology (1986)
META-ANALYSIS OF DRUG-COATED BALLOON VERSUS STANDARD BALLOON ANGIOPLASTY FOR TREATMENT OF INFRAPOPLITEAL LESIONS IN CRITICAL LIMB ISCHEMIA
Authors: Daniel Garcia, Mohammad Ansari, Rhanderson Cardoso, Cesar Mendoza-Trauco, Larry Diaz-Sandoval, Fadi Saab, Jihad Mustapha
Journal: Journal of the American College of Cardiology (2016)
Cilengitide in patients with newly diagnosed glioblastoma multiforme and unmethylated MGMT gene promoter: Protocol of a multicenter, randomized, open-label, controlled phase II study.
Authors: L. B. Nabors, K. Fink, D. A. Reardon, G. J. Lesser, J. Trusheim, S. N. Raval, C. Hicking, M. Picard, T. Mikkelsen
Journal: Journal of Clinical Oncology (2010)

TPS151 Background: Expected median survival is poor for patients with glioblastoma multiforme (GBM). Cilengitide, an investigational selective αvβ3/5 integrin inhibitor, has demonstrated antitumor activity against GBM in previous phase II studies. CORE (cilengitide in combination with temozolomide [TMZ] and radiotherapy [RTX]) will assess the efficacy and safety of 2 regimens of cilengitide in GBM patients with an unmethylated MGMT promoter. The study is a companion trial to CENTRIC, which includes patients with newly diagnosed GBM with methylated MGMT promoter. Methods: CORE is a phase II, randomized, multicenter, open-label, controlled, trial investigating 2 regimens of i.v. cilengitide in combination with standard therapy [RTX/TMZ then TMZ; Stupp et al NEJM 2005] vs standard therapy alone (2:2:1 ratio). The 2 cilengitide regimens compare 2,000 mg twice weekly vs. 2,000 mg 5 times weekly on each day of RTX during 6 weeks of RTX/TMZ, followed by cilengitide 2,000 mg twice-weekly combined with TMZ, followed by cilengitide monotherapy. Study duration will be 3.5–4 years, incorporating a safety run-in, a randomized phase and 21-month follow-up. Eligible patients will be ≥ 18 years old, with newly diagnosed unmethylated MGMT gene promoter status, postoperative gadolinium-enhanced magnetic resonance imaging, stable or decreasing dose of steroids, interval of 2–7 weeks after surgery or biopsy before first administration of study therapy and Eastern Cooperative Oncology Group performance score 0- 1. The primary objective is safety of cilengitide with standard therapy during the safety run-in, and OS time in the randomized phase II with 2 regimens of cilengitide. Secondary objectives include progression free survival and pharmacokinetics. The study began in 2009 with patients across 85 centers screened for unmethylated MGMT gene promoter status, to identify 9–18 patients for the safety run-in and at least 210 patients for the randomized study. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck KGaA EMD Serono, Merck KGaA Merck KGaA EMD Serono, Merck KGaA EMD Serono, Merck KGaA
CERA (Continuous Erythropoiesis Receptor Activator) in patients with multiple myeloma: An exploratory phase I–II dose escalation study
Authors: A. Dmoszynska, J. Kloczko, M. Rokicka, A. Hellmann, I. Spicka
Journal: Journal of Clinical Oncology (2004)

6552 Background: Preclinical/phase I studies indicate that CERA has distinct properties that point to a unique mechanism of action and potent erythropoietic activity both in magnitude and duration of action. This study aimed to identify a suitable CERA dose range for further clinical testing in patients with cancer-related anemia. Methods: This was an open-label, exploratory, multicenter, dose-escalation study in patients (≥18 y) with multiple myeloma (receiving chemotherapy) and with anemia (Hb ≤11 g/dL). Patients (n=64, in groups of 8–10) received CERA SC once every 3 wk for 6 wk (core period), with an optional extension to 12 wk. Initially patients were randomized to receive doses of 2.0, 3.5 or 5.0 μg/kg. Following review of efficacy and safety data, additional patients were assigned sequentially to doses of 6.5 and 1.0 μg/kg, then 8.0 and 4.2 μg/kg. Demographics were similar in all subgroups of patients. The primary efficacy variable was Hb change from baseline to end of initial treatment (completion of the core study period, transfusion or dose change) as assessed by regression analysis. Pharmacokinetic (PK) parameters were assessed throughout. Results: CERA produced a rapid, clinically relevant, dose-related increase in Hb with a trend for a plateau in response at doses of 5.0–8.0 μg/kg. During the core period, CERA 3.5–8.0 μg/kg produced a mean Hb increase of 1.6–2.3 g/dL; 50–62.5% of patients had a response of ≥2 g/dL; levels were maintained or improved during the following 12 wk. PK measurements will be reported. AEs attributed to CERA were rare (4 hypertension, 1 pyrexia) during the core period. There were no unusual clinical and laboratory measurements. No evidence of antibody development was observed. Conclusions: In patients with multiple myeloma, CERA administered once every 3 wk was generally well tolerated and produced a rapid and sustained increase in Hb, which was consistent with its prolonged serum half-life. The long dosing interval of CERA may enable administration on the same dosing schedule as chemotherapy agents and offers flexibility and convenience in the treatment of patients with cancer-related anemia. No significant financial relationships to disclose.
The tumor microenvironment and Immunoscore are critical determinants of dissemination to distant metastasis
Authors: Bernhard Mlecnik, Gabriela Bindea, Amos Kirilovsky, Helen K. Angell, Anna C. Obenauf, Marie Tosolini, Sarah E. Church, Pauline Maby, Angela Vasaturo, Mihaela Angelova, Tessa Fredriksen, Stéphanie Mauger, Maximilian Waldner, Anne Berger, Michael R. Speicher, Franck Pagès, Viia Valge-Archer, Jérôme Galon
Journal: Science Translational Medicine (2016)

Local lymphatic vessel density and immune cytotoxicity prevent metastatic invasion.
High dose chemotherapy followed by autologous stem cell transplantation for relapsed or refractory Hodgkin’s lymphoma
Authors: D. W. Holland, B. G. Engelhardt, S. A. Goodman, J. P. Greer, D. S. Morgan, F. G. Schuening, S. Wolff, R. Bitting, P. Sulur, R. S. Stein
Journal: Journal of Clinical Oncology (2006)

7552 Background: High dose chemotherapy (HDT) followed by autologous stem cell transplantation (ASCT) can produce long-term durable remissions in patients (PTS) with relapsed or refractory Hodgkin’s lymphoma (HL). We investigated whether previously reported prognostic factors could predict overall survival (OS) and progression free survival (PFS) in a modern cohort of PTS, and attempted to identify any subgroup with a particularly inferior survival. Methods: A retrospective chart review was performed on all PTS with relapsed or refractory HL who received HDT and ASCT at a single institution. Results: From 1990 to 2001, 115 PTS received HDT followed by ASCT for relapsed or refractory HL. 76/109 PTS (70%) had achieved a complete response to initial therapy. Median time from initial therapy to relapse (TTR) was 18 months (range, 0–220 months). 105 PTS (91%) received HDT with cyclophosphamide, BCNU, and VP-16. The source of stem cells was bone marrow in 68 PTS (59%) and peripheral blood in 47 PTS (41%). Five year PFS and OS were 46% and 58%, respectively, with a median follow-up of 58 months (range, 1–175 months). The five year PFS and OS of the 13 PTS (11%) with primary refractory disease was 39% and 54%, respectively, not significantly different. 59 PTS (51%) died after HDT and ASCT. The most common cause of death was relapsed HL. Regimen related mortality accounted for 8 deaths (7%). Male gender and TTR &lt;12 months were associated with decreased OS by univariate analysis (P = 0.04 and P = 0.03, respectively). Similar, but non-significant trends were noted in PFS. In multivariate analysis, only TTR &lt;12 months was associated with a statistically significant decrease in OS (P = 0.04). Five year OS for patients with TTR &lt;12 and ≥12 months was 44% and 63%, respectively. Second malignancies occurred in 9 PTS (8%). The most common diagnosis was myelodysplastic syndrome/acute myelogenous leukemia [n = 6 (67%)]. Conclusions: We have confirmed that HDT and ASCT produces long-term PFS and OS in a proportion of PTS with relapsed or refractory HL. TTR &lt;12 months was associated with a statistically significant decrease in OS by multivariate analysis; however, no group of PTS, including those with primary refractory disease, could be identified who did not benefit from HDT and ASCT. No significant financial relationships to disclose.
Hypoxia-related markers in the plasma of patients with advanced non-small cell lung cancer (NSCLC) and survival from chemotherapy: Southwest Oncology Group (SWOG) S0003
Authors: I. V. Galvin, P. N. Lara, Q. Le, K. Chansky, J. J. Crowley, S. Williamson, D. R. Gandara, P. H. Gumerlock
Journal: Journal of Clinical Oncology (2004)

7146 Background: SWOG 0003 is a recently completed phase III trial of carboplatin and paclitaxel +/- tirapazamine (TPZ) in advanced NSCLC. Tumor hypoxia is associated with increased resistance to chemotherapy and radiation. TPZ is a selective hypoxic cytotoxin, which is bioreduced under hypoxic conditions creating DNA damaging radicals. Hypoxia-induced genes that encode secreted proteins include plasminogen activator inhibitor-1 (PAI-1), vascular endothelial growth factor (VEGF) and osteopontin (OPN). Tumor tissue levels of PAI-1, VEGF and OPN have prognostic value in several tumor types. We hypothesized that modulation of plasma levels of one or more markers may correlate with patient outcome. Methods: To date, plasma from 144 patients has been analyzed by ELISA for baseline levels of these proteins. Paired pre- and on-treatment specimens were available from 52 patients. Results: The median level of PAI-1 in all patients decreased from 104 to 59 ng/ml (p=0.00013, paired T test). There was concordance of PAI-1 and VEGF (abnormal or normal) in 80% cases (p<0.0001, Chi-square). Patients whose levels remained normal or normalized during treatment: PAI-1 20/51 (39%), VEGF 23/52 (44%), OPN 26/51 (51%). Patients with overexpression of OPN (cutoff: 784 ng/ml) had a median survival of 6 months vs. 10 months for those with less (p<0.0001). Conclusions: Plasma levels of hypoxia-related biomarkers may have predictive value for patient outcome following chemotherapy plus TPZ. Correlations with patient subsets, treatment arms, demographics, histology, response and survival are ongoing. (CA32102, CA38926, CA46441, ACS-CRTG#19701CCE, The Hope Foundation, Sanofi) Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Sanofi
Correlation of levels of serum 25-hydroxyvitamin D (25-OHD) and lymph node positivity in operable breast cancer: A Turkish Oncology Group study.
Authors: M. K. Altundag, F. Icli, S. Aksoy, O. B. Oksuzoglu, Y. Y. Ozisik, H. Onur, G. Utkan, N. Zengin, N. Alkis, B. Yalcin
Journal: Journal of Clinical Oncology (2010)

627 Background: Vitamin D deficiency is associated with increased breast cancer risk and decreased breast cancer survival. The purpose of this study was to to determine the prevalance and prognostic role of vitamin D deficiency, as measured by serum 25-hydroxyvitamin D (25-OHD), in women at initiation of adjuvant treatment for breast cancer. Methods: Up to now, 407 women with stages I to III breast cancer were enrolled into the study between December 2008 and December 2009. On enrollment, data on demographics, reproductive and menstrual history, tobacco exposure, alcohol intake, medications taken, and tumor characteristics were collected. Serum samples were stored at –80°C until measurement. The distribution of serum 25-OHD levels was categorized as deficient (< 10 ng/mL), insufficient (10 to 25 ng/mL), and sufficient (25-80 ng/mL). Results: The mean age was 49.1 ± 11.7. Of all 407 breast cancer patients, 7.0% of them were premenopausal, 50.5% premenopausal and 42.5% postmenopausal. The percentage of patients with vitamin D deficiency and insufficiency were 54.1% and 33.8%, respectively. Only 12.1% of the patients had sufficient level of vitamin D. There were no significant associations between serum vitamin D level and tumor size (T1-2 vs. T3-4), hormone receptor status, HER-2 expression. However, we found a significant association between serum vitamin D level and lymph node status. Serum vitamin D level was significantly lower in breast cancer patients with positive lymph node (11.8 ± 8.8 vs. 15.2 ± 11.3, p = 0.004). Conclusions: Vitamin D deficiency is common among patients with breast cancer. We found a significant association between serum vitamin D level and lymph node status. Follow-up for 5 years is planned to determine the prognostic role of serum 25-OHD levels. No significant financial relationships to disclose.
Long term disease control in taxane-refractory metastatic breast cancer treated with <i>nab</i> paclitaxel
Authors: J. L. Blum, M. A. Savin, G. Edelman, J. E. Pippen, N. Robert, J. Sandbach, S. Carrasco, J. A. O'Shaughnessy
Journal: Journal of Clinical Oncology (2004)

543 Background: nanoparticle albumin bound (nab) paclitaxel (ABI-007, Abraxane, ABX) is a novel, cremophor-free paclitaxel preparation with a high therapeutic index that does not require pre-medication. Methods: We have conducted a Phase II study of weekly ABX in patients with taxane-refractory, measurable metastatic breast cancer (MBC). Patients received ABX 100mg/m2 weekly over 30 minutes on day 1, 8, and 15 on a 28-day cycle without pre-medication. Results: 106 patients have been enrolled and 66 patients are currently evaluable for toxicity and response. Patients were considered taxane-refractory if they had progressive MBC while receiving paclitaxel, docetaxel or both (59 patients); or if they had relapsed within 12 months of adjuvant taxane (7 patients). Median age was 53 (range, 34–75); median number of metastatic sites was 3 (range, 1–6); 31 (47%) patients have hormone receptor positive MBC; median number of prior chemotherapy regimens (metastatic setting) was 3 (range, 1–10). Thirty-five (53%) patients were treated with docetaxel and 40 (61%) patients received paclitaxel for MBC; 21 (32%) patients received an adjuvant taxane. Based upon AE reporting the only treatment related (TR) Grade (GR) 4 toxicity was neutropenia, occurring in 5 (8%) patients; there was 1 case of febrile neutropenia. Other TR toxicities included: GR 3 nausea, infection (3 patients); GR 2: fatigue, vomiting (2 patients each); GR 1 constipation, dehydration, diarrhea, edema, mucositis and sensory neuropathy (1 patient each). Among the 66 evaluable patients, 13 (20%, 95% CI: 10–29%) had PR. Seven responding patients and 3 additional patients with stable disease (total of 10 patients, 15%, 95% CI: 7–24%) have continued on ABX without progression for ≥ 24 weeks; 5 of these patients are still on treatment with ABX for > 1 year. Conclusion: ABX has an excellent safety profile and resulted in long term disease control in heavily pretreated patients with taxane-refractory MBC. Based upon these results, this study has been amended to treat additional patients using this schedule at an increased dose of 125 mg/m2. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration American Bioscience, Inc.