tbuckley/cabot-search huggingface dataset:
Abstract 19135: Safety and Efficacy of Intramyocardial Delivery of Stem Cells in Ischemic Heart Failure: An Individual Patient Data-Based Meta-Analysis
Authors: Mariann Gyöngyösi, Evgeny Pokushalov, Martin W Bergmann, Jens Kastrup, Douwe Atsma, Christer Sylven, Gerald Maurer
Journal: Circulation (2012)

Background. Intramyocardial stem cell delivery mode might be the choice for regeneration of chronic myocardial ischemia and/or left ventricular (LV) dysfunction. Methods. Individual patient data-based meta-analysis includes data of 383 patients (part of MESS database, clinicaltrials.gov NCT01098591 ) with ischemic cardiomyopathy (iCMP) and treated either with autologous stem cell (SC) (bone marrow mononuclear or mesenchymal stem cells) using percutaneous 3D NOGA-guided delivery (n=290) or randomized to controls (n=93), data received from 5 European centers. Results. The average follow-up (FUP) was 6.4±2.2 months. The baseline end-diastolic volume (189±73 ml vs 201±71 ml) and ejection fraction (EF) (41.4±14.5% vs 42.5±18.7%) were similar in SC treated vs controls. Procedural complication occurred in 2.1% of patients, and 80.8x10^6 cells were delivered in 11.2±2.5 myocardial sites. Compared with controls, intramyocardial delivery of SC improved (p&lt;0.001) LV EF (mean difference 4.6%; 95% confidence interval /CI/ 6.4% to 2.7%); reduced infarct size (-2.22%; 95% CI -3.54% to -0.90%) and size of stress-induced myocardial ischemia (-5.6; 95% CI -7.38% to -3.88%). The CCS angina status (-1.0; 95% CI -0.68 to -1.06) and NYHA (-0.74; 95% CI -0.54 to -0.93) improved significantly (p&lt;0.001) post SC therapy as compared with controls. Kaplan-Meier analysis resulted in a significant better survival (98.8% vs 93.5%, p&lt;0.01) and MACCE-free survival (97.9% vs 78.5%, p&lt;0.001) rate in SC-treated patients vs controls. Multivariate analysis resulted in a lower baseline EF and higher total number of intramyocardial delivered SC as significant predictors for improvement in EF, while norminal regression analysis revealed SC therapy as significant predictor for MACCE-free survival in patients with iCMP. Conclusion. Meta-analysis of 3D NOGA endocardial mapping guided transendocardial stem cell treatment proves the safety and efficacy of this cardiac regeneration strategy in patients with chronic ischemia and low EF.
Gemcitabine plus paclitaxel and gemcitabine plus docetaxel in first- or second-line metastatic breast cancer: A phase II randomized trial
Authors: R. V. Boccia, L. Vaughn, H. Zeigler, Y. Wang, J. Gill, A. Melemed, O. Shonukan
Journal: Journal of Clinical Oncology (2007)

1046 Background: The combination of gemcitabine (G) with paclitaxel (P) has proven efficacy in the first-line treatment of metastatic breast cancer (MBC). In addition, the combination of G with docetaxel (D) has shown activity in several nonrandomized, Phase II, MBC trials. This randomized Phase II trial was conducted to assess the efficacy and safety of G plus P and G plus D combination regimens in previously treated patients with MBC. Methods: Patients with locally advanced or metastatic breast cancer were randomized equally into two groups to receive either GP (G 1,250 mg/m 2 IV on Days 1 and 8 plus P 175 mg/m 2 IV on Day 1) or GD (G 1,000 mg/m 2 IV on Days 1 and 8 plus D 75 mg/m 2 IV on Day 1). Treatment was administered every 21 days and continued until disease progression or undue toxicity. Planned enrollment was 112 patients (56 per group). The primary study objective was tumor response assessed using RECIST criteria. Toxicities were assessed using the NCI Common Toxicity Criteria, Version 2.0. Results: Twenty-five patients were enrolled in each treatment group and accrual was stopped due to slow enrollment. In the GP group, only 23 patients were evaluable for response and 24 patients were monitored for safety. One patient did not receive study medication and was not assessed for efficacy or safety. A second patient was determined to have nonmeasurable disease at baseline and was not assessed for response. Overall response rate was 39% (95% CI 20, 61) for the GP group and 40% (95% CI 21, 61) for the GD group. The median number of cycles administered was 6.5 in the GP group and 6.0 in the GD group. Detailed study results are summarized in the table below. Conclusions: These results show that GP and GD combination regimens are both efficacious in the treatment of MBC, with similar response rates and manageable toxicity profiles. [Table: see text] No significant financial relationships to disclose.
Abstract 9882: Post-Exercise Blood Pressure Predicts Future Cardiovascular Mortality in Asymptomatic Individuals
Authors: Janky Patel, A. R Sharrett, Roger S Blumenthal, Samia Mora
Journal: Circulation (2012)

Background: Non-electrocardiographic parameters obtained from exercise testing, including exercise capacity, exercise blood pressure, chronotropic response, and heart rate recovery, are clinically useful in determining prognosis in asymptomatic individuals. We hypothesized a relationship between post-exercise blood pressure (BP) and CVD mortality. Methods and results: After performing submaximal Bruce treadmill tests, a total of 6,451 asymptomatic North American study participants (56% males, mean age 44) from the Lipid Research Clinic Prevalence Study were prospectively followed for 20 years (366 CVD deaths). Post-exercise BP was the measured BP taken after ceasing exercise for 2 min, 4 min, and 6 min for systolic (SBP) and diastolic (DBP). The association of CVD mortality was stronger for post-exercise SBP (4 min age- and sex-adjusted hazard ratio 1.42 [95% CI, 1.28-1.55] per 1-SD increment [21 mmHg]) than post-exercise DBP (1.26 [1.14-1.38] per 1-SD increment [12 mm Hg]). After multivariate adjustment, post-exercise DBP was not associated with CVD mortality. By contrast, post-exercise 2 min, 4 min, and 6 min SBP were each positively associated with CVD mortality, with the post-exercise 4 min SBP having the greatest magnitude of risk. After adjusting for standard risk factors, baseline BP, heart rate recovery, and exercise capacity, the adjusted hazard ratios (95% CIs) for increasing quartiles of post-exercise 4 min SBP were 1.00 (reference), 1.47 (0.94-2.31), 1.75 (1.15-2.66) and 2.21 (1.43-3.43), p for trend&lt;0.001 (Table). Conclusion: Elevated post-exercise SBP was significantly associated with CVD mortality in asymptomatic individuals independent of other risk factors, including baseline BP. A post-exercise 4 min SBP greater than 150 mmHg identifies higher risk individuals who may warrant more aggressive treatment than is currently recommended.
Abstract 19807: Increased Triacylglycerol Synthesis in the Heart Improves Functional Recovery After Ischemia
Authors: Stephen C Kolwicz, Li Liu, Ira J Goldberg, Rong Tian
Journal: Circulation (2012)

Accumulation of cardiac lipids has been associated with cardiac dysfunction in diabetes and obesity while increased muscle lipid storage in athletes is associated with improved function. We have previously shown that cardiac specific overexpression of diacylglycerol acyltransferase 1 (MHC-DGAT1), the rate limiting enzyme for triacylglycerol (TAG) synthesis, enhances TAG synthesis, reduces ceramide formation, and rescues lipotoxic cardiomyopathy. Using MHC-DGAT1 mice, we tested whether increased TAG synthesis and storage affected cardiac responses to ischemia-reperfusion. A doubling of cardiac TAG content in MHC-DGAT1 (P&lt;0.05; n=4) was not associated with in-vivo cardiac dysfunction or heart size. With dynamic 13C NMR spectroscopy we found a 70% increase of incorporation of 13C labeled fatty acids (FA) into the cardiac TAG pool in MHC-DGAT1 hearts. In isolated Langendorff perfused hearts, rate pressure product (RPP), was similar in MHC-DGAT1 and control (CON) hearts at baseline (BL). When subjected to 25min of no-flow ischemia (ISC), end diastolic pressure rose equivalently in both groups. However, recovery of RPP during reperfusion (REP) was significantly improved in MHC-DGAT1 compared to CON (51±6% vs 28±6%; n=5-6). At the end of REP, 13C NMR spectroscopy of heart extracts suggested decreased exogenous FA oxidation with no change in glucose oxidation in MHC-DGAT1 hearts. Cardiac TAGs, measured in freeze-clamped hearts, remained unchanged in CON during BL, at end ISC, and at end REP (n=3 per time point). Interestingly, despite ~2-fold increase in TAG in MHC-DGAT1 at BL, TAG content depleted to levels similar to CON at end ISC and REP, inferring accelerated TAG lipolysis in MHC-DGAT1 during the ischemic period. Non-esterified fatty acid (NEFA) concentration was not different between the groups at any time point. In conclusion, these results suggest that ischemia-induced activation of lipolysis in MHC-DGAT1 hearts improves functional recovery, in part, by increasing the oxidation of endogenous lipids during reperfusion. These data also suggest a potential secondary role of endogenous lipids to act as signaling molecules to modulate cardiac function.
Xenograft-like destruction of tumors and their conversion into vaccines by intratumoral injection of α-gal glycolipids
Authors: U. Galili, K. Wigglesworth, U. Abdel-Motal
Journal: Journal of Clinical Oncology (2007)

3074 Background: We describe a novel immunotherapy exploiting the natural anti-Gal antibody to destroy tumors and convert them into endogenous vaccines. Anti-Gal constitutes 1% of immunoglobulins in humans and interacts specifically with a-gal epitopes (Gala1- 3Galβ1–4GlcNAc-R) on glycolipids and glycoproteins. a-Gal epitopes are abundant in nonprimate mammals. Binding of anti-Gal to a-gal epitopes on pig cells mediates xenograft rejection. We inject glycolipids carrying a-gal epitopes (a-gal glycolipids) into solid tumors. Methods: a-Gal glycolipids extracted from rabbit RBC have carbohydrate chains capped with a-gal epitopes. Efficacy of treatment was studied in a1,3galactosyltransferase knockout mice bearing B16 melanoma. These mice are unique since they lack a-gal epitopes and can produce anti- Gal, like humans. Also B16 cells lack a-gal epitopes. B16 lesions (∼5 mm) were injected with 1mg a-gal glycolipids. Results: Intratumoral injection of a-gal glycolipids results in local inflammation mediated by anti-Gal binding to the ∼2x10 16 a-gal epitopes on these glycolipids, activation of complement and generation of chemotactic factors. a-Gal glycolipids insert spontaneously into tumor cell membranes. Binding of anti-Gal to a-gal epitopes on such tumor cells induces lesion destruction, similar to xenograft rejection. Anti-Gal further opsonizes tumor cells for effective uptake by inflammation recruited dendritic cells (DC), via Fcγ receptors of these APC. The DC transport internalized tumor Ags to draining lymph nodes and present tumor Ag peptides, thus activating tumor specific T cells and eliciting an immune response against micrometastases. Conclusions: Injected a-gal glycolipids effectively destroy lesions and convert them into vaccines. This treatment may be even more effective in humans, since complement activity is much higher than in mice. This treatment may also be considered as neo-adjuvant immunotherapy for converting primary tumor into autologous tumor vaccine that elicits a protective immune response against micrometastases, during the period preceding resection of the tumor. No significant financial relationships to disclose.
Subcutaneous amifostine for reduction of radiation xerostomia in nasopharynx cancer: A prospective randomised study
Authors: S. F. Leung, P. Teo, B. Zee, M. Kam, P. Choi, E. Hui, F. Mo, M. Lai, W. H. Kwan, A. T. c. Chan
Journal: Journal of Clinical Oncology (2005)

8043 Background: Xerostomia is the most common long-term toxicity after radiation therapy (RT) for nasopharynx cancer (NPC). Amifostine (AF) has recognised benefit in reduction of radiation xerostomia for head and neck cancers. However, there has been no randomized study specifically addressing the impact of AF on RT for NPC, and data on the use of subcutaneous amifostine is limited. Methods: Treatment naïve NPC patients whose primary treatment was conventional RT without chemotherapy were randomized to either RT only or RT plus amifostine (RT+AF). Patients in RT+AF arm received subcutaneous amifostine 500mg before each RT treatment during a 6.6–8.6 week course of RT. Primary endpoint was RTOG acute (at 4 weeks after RT), and chronic (at 1 year after RT) xerostomia grade (proportion of grade 2 xerostomia). Secondary endpoints were total salivary flow rates and scoring on a 6-item xerostomia questionnaire. Planned sample size was 28 patients in each arm, to detect a 40% reduction of grade 2 or worse xerostomia (assumed to occur in >=80% of patients in Arm-RT) with 80% power for alpha=0.05. Results: 49 patients were recruited, 3 patients were withdrawn before commencement of treatment, four patients had died of metastatic NPC, including one before completion of RT. 45 patients were evaluable for acute xerostomia and 37 patients for chronic xerostomia. Patients in RT+AF had significantly less grade 2 chronic xerostomia (8/17 vs 19/20, p=0.002, Fisher’s Exact Test) while the acute xerostomia grades were similar in both arms. The scores on the xerostomia questionnaire and the total saliva flow rates were similar in both arms, both at the early post-RT and 1 year post-RT time points. Conclusions: Subcutaneous amifostine reduces the occurrence of severe xerostomia as assessed by RTOG grading at one year after RT for NPC. No significant financial relationships to disclose.
Expression of stem cell markers in circulating melanoma cells
Authors: A. Fusi, A. Busse, S. Ochsenreither, A. Rietz, U. Keilholz
Journal: Journal of Clinical Oncology (2009)

e22056 Background: Within circulating tumor cells there may be a subset of cell with stem cell (tumor initiating) characteristics able to develop distant metastasis. Several markers including nestin and CD133 have been found to be possible candidates to identify such a kind of subpopulation in other experimental models. We evaluated the presence of melanoma cells bearing stem cell phenotype in the bloodstream of patients with cutaneous or uveal melanoma after depletion of the leukocytes fraction. Methods: Between 50 and 100 ml of peripheral blood were collected from 12 melanoma patients with various tumor burden as well as three healthy volunteers. Blood samples were enriched for tumour cells by CD45 depletion of the leukocyte fraction using magnetic beads separation (EasySep, Stem Cell Technologies. Inc.). The remaining material was stained with antibodies for the markers Melan-A/Mart-1 (Dako) and HMB45 (Dako), CD133 (Miltenyi Biotec) and nestin (R&amp;D System) and analysed by flow cytometry (BD FACSCalibur). Ten ml of blood were further processed and CD133, nestin, Melan-A/Mart-1 transcripts were quantified by Real Time RT-PCR (LightCycler, Roche Diagnostic). Results: CD45-depleted fractions in healthy controls were negative for melanoma markers. Melan-A/Mart-1 and/or HMB45 positive cells were detectable in 11 out of 12 melanoma patients. The absolute number of melanoma cells identified ranged from 6 to 176 per 10 ml of blood. Nestin expressing cells were more represented compared to CD133 expressing cells (median 27.4%, range 0.3% to 65.1% vs. median 9.3%, range 0.1% to 16.8%) within the melanoma fraction of cells positive for Melan-A/Mart-1 and/or HMB45. In one patient two different melanoma cell populations were detectable. The population of cells with lower expression of the melanoma markers showed at the same time higher expression of nestin and CD133 (5.9% vs. 1.3% and 10.2% vs. 6.7% respectively). Nestin results were in good accordance to the FACS data (nestin: r=0.55; CD133: r=0.23; Pearson test). Conclusions: The novel negative separation technique allows reliable isolation of melanoma cells from peripheral blood of patients with metastatic disease. A significant fraction of melanoma cells in peripheral blood bears a stem cell phenotype. No significant financial relationships to disclose.
Influence of measurement error on assessment of response to anticancer chemotherapy: proposal for new criteria of tumor response.
Authors: D Warr, S McKinney, I Tannock
Journal: Journal of Clinical Oncology (1984)

The decision to use a given type of chemotherapy to treat cancer patients is often based on the prior demonstration that a proportion of similar patients has "responded" in a clinical trial. Most responses are recorded as a partial shrinkage of tumor, defined usually as a greater than 50% shrinkage of the sum of cross-sectional areas of index lesions for at least one month. The errors in categorization of response have been estimated by comparing measurements of several physicians on real or simulated malignant lesions. False categorization of partial response based on a comparison of two measurements of the same lesion was 1.3% and 12.6% for large and small simulated nodules, respectively, 13.1% for malignant neck nodes, and 0.8% for metastatic lung nodules. Partial response for hepatic lesions has been defined by a 50% or 30% decrease in liver span below the costal margin; these definitions led to a false categorization of partial response of 8.5% and 18.4%, respectively. Larger errors are evident when using the current definition of disease progression that requires only a 25% increase in area. False categorization of response is increased by comparing any of serial measurements with the initial lesions, as is usually done clinically. Many published trials have used criteria for response that are subject to large errors; an uncritical interpretation of their results may lead to inappropriate treatment of patients. Based on the results, new criteria for evaluating tumor response are proposed.
Modeling bone mineral density (BMD) evolution in postmenopausal patients treated by letrozole (L), tamoxifen (T), and sequences of T and L (SAKK 21/07)
Authors: K. Zaman, B. Thürlimann, J. Huober, A. Schönenberger, O. Pagani, J. Lüthi, M. Simcock, A. Giobbie-Hurder, C. Genton, S. Aebi
Journal: Journal of Clinical Oncology (2009)

545 Background: Osteoporosis and fractures are long term complications of aromatase inhibitor use in the adjuvant therapy of breast cancer. Early detection of patients (pts) at risk of treatment-induced osteoporosis may allow preventive therapy and selection of the most appropriate endocrine therapy. We developed a statistical model describing the evolution of BMD in pts treated with T, L and sequences of T and L. Methods: Available dual-energy x-ray absorptiometry exams (DXA) of pts treated in trial BIG 1–98 were retrospectively collected from Swiss centers. Treatment arms: A) T for 5 years; B) L for 5 years; C) 2 years of T followed by 3 years of L; and D) 2 years of L followed by 3 years of T. Pts without DXA were used as a control for detecting selection bias. A repeated measures model using the first-order autoregressive covariance structure to allow for different times between DXA was used to model BMD (g/cm 2 ) since trial randomisation. Prospectively defined covariates were considered as fixed effects in a multivariable model using an intention to treat analysis. Covariates at trial randomization were: age, height, weight, race, known osteoporosis, tobacco use, prior bone fracture, prior hormone replacement therapy (HRT), bisphosphonate use and previous neo-/adjuvant chemotherapy (ChT). Results: A total of 247 out of 546 pts had between 1 and 5 DXA; a total of 576 DXA were collected. Arm A contained 67 pts, B 63 pts, C 55 pts and D 62 pts. Median follow-up was 5.8 years. Factors correlated with BMD in the multivariate analysis were weight (0.003/kg, p &lt; 0.0001), height (0.003/cm, p = 0.0083), osteoporosis (-0.130, p &lt; 0.0001), tobacco (current / previously vs. never: -0.057, p = 0.0011 / -0.042, p = 0.0798), previous HRT (0.030, p = 0.0244), ChT (0.032, p = 0.0174), time since endocrine therapy start (-0.009/year, p = 0.0164) and treatment arm (B / C / D vs. A: -0.068, p = 0.0002 / -0.091, p &lt; 0.0001 / -0.064, p = 0.003). Conclusions: Our statistical model describes the BMD evolution for pts treated with L and/or T. All treatment regimens affect BMD. Contrary to expectation, the switch schedule T followed by L does not seem to result in better bone protection compared to L monotherapy. [Table: see text]
Neoadjuvant chemotherapy in cervix cancer: is it effective?
Authors: H J Long
Journal: Journal of Clinical Oncology (1995)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1995.13.8.2141 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 7636559 Neoadjuvant chemotherapy in cervix cancer: is it effective? H J LongxH J LongSearch for articles by this author https://doi.org/10.1200/JCO.1995.13.8.2141 PDF "Neoadjuvant chemotherapy in cervix cancer: is it effective?." Journal of Clinical Oncology, 13(8), pp. 2141–2142© 1995 by American Society of Clinical Oncology
Phase 1 study of an anti-GD3 monoclonal antibody, (KW-2871) in patients with advanced metastatic melanoma
Authors: J. Shah, A. Forero, R. Carlisle, P. Triozzi, A. Lobuglio, T. Kuwabara, A. Teitelbaum, M. Fujimori, M. Conry
Journal: Journal of Clinical Oncology (2005)

2556 Background: Current therapeutic options for metastatic melanoma are limited. KW-2871 is an IgG1 kappa chimeric monoclonal antibody targeting ganglioside antigen GD3, expressed on neuroectodermal tumors including melanoma, glioma and neuroblastoma. GD3 expression is known to be upregulated with malignant transformation of melanoma and tumor progression. KW-2871 has mediated antibody-dependent cellular cytotoxicity (ADCC). Method: Seventeen patients with stage IV melanoma not amenable to surgical intervention with ECOG performance status of 0, 1 or 2 were enrolled in the study to evaluate the safety, tolerance and pharmokinetics of KW-2871. All patients received a test dose of 10 mg/m2 IV. Patients were stratified into 4 cohorts receiving 4 doses at 2 week interval of 20, 40, 80 and 120 mg/m2. No premedications were administered prior to infusion of KW-2871. Results: No dose limiting toxicities (DLT: grade ≥ 2 allergic reaction and/or Grade ≥ 3 toxicity) were observed in the 20 and 40 mg/m2 cohorts. The first two patients in the 80mg/m2 had DLT’s (grade 3 urticaria, grade 3 seizures, grade 3 edema of the larynx, and grade 3 chest tightness). No patients were enrolled in the 120 mg/m2 cohort. A fifth cohort with 6 patients was then opened at a dose of 60 mg/m2 and this dose level exceeded the MTD (grade 3 urticaria, grade 3 laryngeal edema, and grade 3 chest tightness). KW-2871 had no myelosuppression. The plasma KW-2871 disappearance curves fit a two-compartment model best. The mean T1/2 beta at 40 mg/m2 dose level was 13±6 days (range: 8–21 days). The mean AUC at 40 mg/m2 was 3965 mcg*hr/ml. Two patients in the 40 mg/m2 cohort had stable disease for 8 and 3 months. Antibody development against KW-2871 was not detected in the study. Conclusion: An MTD of 40 mg/m2 without pre-medication was established in this initial dose escalation study. A second Phase 1 dose escalation study with the use of premedication including diphenhydramine, corticosteroids and H2 blockers is active currently and will help identify a higher MTD to maximize potential efficacy. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Kyowa