tbuckley/cabot-search huggingface dataset:
Sentinel lymph nodes navigation surgery for stage I or IIA breast cancer patients
Authors: M. Hirata, H. Kawabata, K. Tanaka
Journal: Journal of Clinical Oncology (2006)

10784 Background: We applied indigocarmine for sentinel lymph nodes staining for Stage I or IIA breast cancer patients. We compared patient survival between sentinel lymph nodes navigastion surgery group and ordinary surgery with axillary lymph nodes dissection group. Methods: Patients consisted of 160 histologically proven breast cancer women (Stage I: 108 cases, Stage II: 52 cases, 51.8 ± 11.1 years, SN group) and other 320 breast cacner women (Stage I: 187 cases, Stage II: 146 cases, 53.4 ± 9.7 years, non-SN group). All patients underwent partial resection of their breast with histologically proven cancer cells negative margin (SN group: May 2000–December 2003, non-SN group: January 1996–December 2003). Fifteeen minutes before surgery, 0.4% Indigocarmine (10 ml) was injected around the tumor by use of 24 gauge syringe. Sentinel lymph node (SN) was defined as the stained lymph node. Intra operative cytology and histopathological examination was performed for SN and one or two lymph nodes around the SN. When any cancer cells were found in either of SN or the lymph nodes around the SN, axillary lymph nodes dissection was performed. When all of SN and several lymph nodes around the SN were diagnosed as cancer cells negative, axillary lymph nodes dissection was omitted. Patient survival and disease free survival were calculated by Kaplan-Meier method. Results: About patients characteristics including age, diameter of the tumor, hormone receptor status, treatment after surgery, etc., no significant difference was found between two groups. We could find SN in 156 patients (97.5%) out of 160 cases in SN group. Four years patient survival was 97.6% (stage I, SN group), 96.6% (stage I, non SN group), and 96.6% (stage IIA, SN group), 93.5% (stage IIA, non SN group), respectively (no significant difference). Four years disease free survival was 97.6% (stage I, SN group), 95.4% (stage I, non SN group), and 82.5% (stage IIA, SN group), 86.4% (stage IIA, non SN group), respectively (no significant difference). Conclusions: Sentinel lymph nodes navigation surgery for stage I or IIA breast cancer patients by use of 0.4% Indigocarmine revealed comparable patient survival and disease free patient survival to ordinary surgery. No significant financial relationships to disclose.
Failure of Cultured Human T-Cell Lymphoid Lines to Stimulate in Mixed Leukocyte Culture
Authors: Ivor Royston, Peter R. Graze, R. Bruce Pitts
Journal: JNCI Journal of the National Cancer Institute (1974)

Cultured human lymphoblastoid cell lines, originating from patients with acute lymphoblastic leukemia and possessing thymus-derived (T) lymphocyte characteristics, failed to activate normal allogeneic and xenogeneic (primate) peripheral lymphocytes in “1-way” mixed leukocyte cultures. In contrast, human and nonhuman primate lymphoblastoid cell lines, originating from normal donors and patients with leukemia or lymphoma and having bone marrow-derived (B) lymphocyte characteristics, were potent stimulators of autochthonous, allogeneic, and xenogeneic (primate) peripheral lymphocytes. T-cell lines may be derived from a clone of lymphoid cells which either lacked stimulatory antigens or lost such antigens during leukemogenesis.
Pharmacological evaluation of BM-573, a dual thromboxane A2 receptor antagonist and thromboxane synthase inhibitor, as potential anti-metastatic agent
Authors: X. J. de Leval, T. Dassesse, V. Benoit, Bernard Pirotte, Marie-Paule Merville, Jean-Louis David, Vincenzo Castronovo, Jean-Michel Dogné
Journal: Blood (2003)
The effect of aspirin therapy on circulating vascular endothelial growth factor (VEGF) levels in tamoxifen-treated women.
Authors: C. E. Holmes, J. Jasielec, J. E. Levis, J. Skelly, H. B. Muss
Journal: Journal of Clinical Oncology (2010)

679 Background: Tamoxifen use has been associated with higher levels of serum VEGF. Increased VEGF levels are associated with adverse prognostic markers in women with breast cancer suggesting tamoxifen efficacy might be further improved if VEGF levels could be decreased. Aspirin reduces tissue VEGF production through the inhibition of cyclooxygenase. Aspirin also decreases platelet activation and may decrease the release of VEGF from platelets stimulated in the tumor microenvironment. We examined the effect of short term aspirin use on circulating VEGF levels in women on tamoxifen therapy. Methods: Twelve women receiving tamoxifen for stage 1-4 breast cancer or DCIS were prospectively evaluated. Patients were treated with 325 mg aspirin daily for a total duration of 45 days. Circulating VEGF (plasma, serum) was measured prior to aspirin initiation, following 30 and 45 days on aspirin and 30 days after discontinuation of aspirin. The ability of aspirin to inhibit release of VEGF from platelets was also compared between time points following ex vivo addition of a thrombin receptor agonist (TRAP) to whole blood. VEGF was analyzed by ELISA. Statistical analyses were done using repeated measures analysis of variance. Results: Average circulating VEGF levels prior to initiating aspirin therapy were 484.5 ± 261.0 (serum) and 34.2 ± 16.7 (plasma) in our study population of women who had previously received an average of 14 (range 2-46) months of tamoxifen therapy. Significant differences were detected in serum VEGF levels over time (p > 0.02) with a significantly lower mean level 30 days after completing aspirin therapy (357.2 ± 202.1, as compared to pre- and on-treatment (491.6 ± 293.1, day 30 therapy, 488.3 ± 278.6 day 45 therapy) levels. No differences were detected in mean plasma VEGF levels over time (p > 0.11). Aspirin use resulted in a marginally significant (p > 0.06) decrease in ex-vivo agonist stimulated VEGF release while patients were taking the drug. Conclusions: A short course of aspirin therapy decreased total circulating platelet VEGF levels and decreased agonist stimulated VEGF release in women taking tamoxifen. Further study of the addition of aspirin to tamoxifen regimens is warranted. No significant financial relationships to disclose.
Combination of the immunocytokine F16-IL2 with doxorubicin or paclitaxel in patients with solid tumors: Results from two phase Ib trials.
Authors: F. G. De Braud, C. Catania, A. Onofri, C. Pierantoni, S. Cascinu, M. Maur, C. Masini, P. F. Conte, L. Giovannoni, A. Tasciotti, V. Lovato, D. Neri, H. D. Menssen
Journal: Journal of Clinical Oncology (2011)

2595 Background: F16-IL2 is a tumor-targeting immunocytokine composed of the antibody fragment F16 (specific to the tumor marker A1 domain of tenascin) and of human interleukin-2 (IL2). Thorough preclinical work showed that F16-IL2 localizes selectively at tumor tissues and enhances the activity of certain anticancer drugs. In these phase Ib studies, we investigated F16-IL2 in combination with doxorubicin or paclitaxel, defining the recommended dose (RD) and assessing safety, tolerability, and early signs of activity. Methods: Cohorts of pretreated patients with progressive solid tumors received weekly administrations of 6 escalating doses of doxorubicin (up to 25mg/m2) or 8 escalating doses of paclitaxel (up to 90mg/m2), combined with F16-IL2 (up to 25 MioIU of IL2 equivalent) for a maximum of 6 months. Safety and efficacy were evaluated using CTC v3.0 and RECIST criteria. Results: 18 and 28 patients, with a median age of 63 years (37-75) and 64 years (42-79), were treated in the doxorubicin and paclitaxel combination trials, respectively. Toxicity was manageable with only few reversible G4 events, no serious unexpected adverse reactions, and no treatment related deaths. The RD was defined as 25 MioIU of F16-IL2 given in combination with 25mg/m2 doxorubicin or 90mg/m2 paclitaxel weekly. Objective responses and long-lasting disease stabilizations were observed, including 4 partial responses, 2 of which in heavily pretreated NSCLC patients and 1 still ongoing after 17 months from beginning of treatment. Among the evaluable patients treated with the paclitaxel or doxorubicin combination respectively, PFS rate at 3 months is 50% and 44% (n=24 and n=16) and 1-year survival rate is 41% and 38% (n=17 and n=13). Conclusions: 25 Mio IU of F16-IL2 combined with full-dose doxorubicin or paclitaxel can be safely and repeatedly administered weekly to patients with solid tumors, and showed early signs of clinical activity. Based on preclinical evidence, these combination regimens are being administered to breast cancer patients in phase II trials. Moreover, starting from the observed promising signs of activity, a study of F16-IL2 in lung cancer patients is being planned.
Soluble VEGF and its receptors (1 and 2) in metastatic malignant melanoma patients: Relationship with survival
Authors: C. Soubrane, R. Mouawad, O. Rixe, M. Gatineau, D. Khayat
Journal: Journal of Clinical Oncology (2005)

7541 Background: Vascular endothelial growth factor (VEGF) and its receptors (VEGFRs) play an essential role in tumor angiogenesis and are closely related with malignancies. However, the prognostic significance of the soluble forms of VEGF, VEGF-R1(flt1) a known intrinsic inhibitor of VEGF and VEGF-R2 (flk2) which binds VEGF-A in metastatic malignant melanoma is unclear. Objectives: this study was designed to i) evaluate whether soluble VEGF, VEGF-R1 and VEGFR-2 or the ratio of these parameters play a role in metastatic maliganat melanoma patients and ii) to determine if they have any relationship with overall survival. Methods and Patients: using a sensitive enzyme-linked immunosorbent assays, VEGF-A, VEGF-R1 and VEGF-R2 were measured in sera of 40 patients with a fully documented history of metastatic malignant melanoma in comparison with 15 healthy controls. Overall survival (OS) was calculated from the beginning of treatment until the death and analyzed using the Kaplan-Meier method; curves were compared using the log rank test. Results: Pretreatment median serum VEGF level was significantly higher in MMM patients (20 vs 0 pg/ml) as compared to healthy donors (p=0.001) but no difference was observed regarding median sVEGF-R1 (55 vs 45 pg/ml) or median sVEGF-R2 levels (4888 vs 4821 pg/ml) (p= 0,42, p= 0.73). When we calculated the ratio of VEGF/R1 or VEGF/R2 it was significantly higher in patients (10 and 100 fold; p=0,002; p=0.0003 respectively) compared to healthy controls. In order to establish the possible relationship between VEGF, VEGF-R1 or R2 levels and OS, patients were divided into 2 groups (low and high) using the median level detected in the pretreatment serum as a cut-off. As shown by univariate analysis, only low levels of serum VEGF-R1 was significantly correlated (Χ2=8.03, p= 0.0046) to a higher survival (13,3 vs 6,2 months) but not sVEGF (15.5 Vs 11 months) or circulating VEGF-R2 (8,9 vs 6,9 months) (Χ2=2.44, p= 0.09; Χ2 = 0.71, p= 0.67 respectively). Conclusion: Soluble VEGF-R1 seems to be an interesting parameter for survival in MMM patients. However, further investigation is required in order to confirm this observation. No significant financial relationships to disclose.
Author’s reply to Keatinge and Wong and Cruickshank
Authors: Henrik Møller
Journal: BMJ (2015)

We appreciate the interest and debate that our article has generated in rapid responses and conferences and workshops in the past year.1 2 3 We too thought that the press headlines (mainly arising from a single press agency) were sensationalist and unhelpful.

The concern about lead time contributing to the observed association between urgent referral …
Fortnightly Review: Management of atopic eczema
Authors: P M McHenry, H C Williams, E A Bingham
Journal: BMJ (1995)

<h3>Summary points</h3> Time for explanation and education is essential Adequate amounts of emollients should be prescribed, and these should be used liberally and frequently When prescribing topical corticosteroids the age of the patient, the site to be treated, and the extent of the disease are important considerations Deterioration in previously stable eczema may be due to secondary bacterial or viral infection or to development of a contact dermatitis Attempts to eradicate the house dust mite are not currently recommended Dietary restriction is of little or no benefit in adults, and in children it is worth trying only in selected infants under professional supervision Evidence for the therapeutic value of evening primrose oil remains inconclusive PUVA or UVB may be helpful in selected patients
Single-photon emission computed tomography gallium imaging versus computed tomography: predictive value in patients undergoing high-dose chemotherapy and autologous stem-cell transplantation for non-Hodgkin's lymphoma.
Authors: J M Vose, P J Bierman, J R Anderson, K A Harrison, G V Dalrymple, K Byar, A Kessinger, J O Armitage
Journal: Journal of Clinical Oncology (1996)

PURPOSE To evaluate the predictive value of computed tomography (CT) scanning and single-photon emission computed tomography (SPECT) gallium (Ga) scanning in the disease-free survival of patients receiving high-dose chemotherapy and autologous stem-cell transplantation for non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS One hundred forty-three patients undergoing transplant for NHL underwent CT scanning of chest, abdomen, and pelvis, and a SPECT Ga scan before transplantation and at day + 100 after transplant. The failure-free survival (FFS) by scan result was analyzed. RESULTS In the diffuse aggressive lymphoma patients, the 1-year FFS for patients having a positive SPECT Ga scan at day + 100 was 15% compared with a 3-year FFS of 47% for those with a negative scan (P &lt; .001). Patients with a positive CT scan at day + 100 had a 36% 3-year FFS, and those with a negative CT scan had a 39% 3-year FFS (P = not significant [NS]). An analysis of the combination of CT scan and SPECT Ga scan results at day + 100 posttransplant demonstrated a 3-year FFS of 14% if they were both abnormal; if the CT was positive and Ga was negative, the 3-year FFS was 68%; positive Ga with a negative CT was 25%; and both negative was 34% (P = .0015). For the patients with follicular NHL, those with a positive SPECT Ga at day + 100 had a 14% 1-year FFS compared with those with a negative scan, who had a 45% 3-year FFS (P &lt; .001). In the follicular NHL patients, the 3-year FFS of those with a positive CT was 17% compared with a 64% 3-year FFS for patients with a negative CT scan (P &lt; .001). CONCLUSION The use of SPECT Ga scan at day + 100 posttransplant for evaluation of disease activity in patients with diffuse aggressive NHL was highly predictive of eventual outcome and was more predictive than the CT scan results. However, for patients with follicular NHL, the addition of SPECT Ga scanning to CT scanning did not add substantially to the evaluation of transplant outcome.
Assessing the impact of comorbidities on autologous hematopoietic cell transplant (AHCT) outcomes using the hematopoietic cell transplant-comorbidity index (HCT-CI) in lymphoma
Authors: M. Kassar, S. A. Gregory, K. Shell, P. Venugopal, J. Shammo, M. I. Farhat, M. Batus, A. Law, H. C. Fung
Journal: Journal of Clinical Oncology (2007)

7102 Background: Sorror et al. has identified HCT-CI as a valid scoring of pretransplant comorbidities that predicted nonrelapse mortality and survival after allogeniec HCT. We recently reported on the validity of HCT-CI in predicting morbidity outcomes after AHCT for lymphoma (BBMT in press). High HCT-CI score predicted for prolonged hospitalization and high incidence of hospital re-admission after AHCT. The objective of this study is to evaluate the impact of HCT-CI on mortality risk after AHCT. Methods: We included pts above age of 40 with advanced HL or NHL, who underwent AHCT in our institution between 01/98 &amp; 05/06. Median follow up was 29.4 mo. Pts were assigned scores based on the HCT-CI. Defenition of comorbidities were recently reported (Kassar et al, BBMT in press). Results: 80 pts were included (NHL: 74, HL: 6). 61 pts were male. Median age was 56 years (42–76). Comorbidities (points, prevalence%): mild hepatic (1,14), cardiac (1,15), cerebrovascular (1,4), arrhythmia (1,9), moderate pulmonary (2,11), severe pulmonary (3,8), rheumatologic (2,5), DM (1,23), inflammatory bowel disease (1,3), psychiatric (1,11), infection (1,6), obesity (1,11), and renal (2,1). Median HCT-CI was 1 (0: 37 %, 1: 26%, 2–7: 37%). 22 pts died: 15 from relapse and 7 from non relapse mortality (NRM) causes. Cumulative day-100 NRM and 1-year NRM rates are: 1.3% and 4%, respectively. Pts were categorized into 2 groups: low-risk (scores of 0–1) and high-risk (scores 2–7). Using Cox Regression model and adjusting for age and histology, low-risk group had a significantly better OS (1 wk-58.6 mo, median 34.1 mo) compared to high-risk group (5 days-23.6 mo, median 6 mo) (HR: 3.73, p = .01, 95% CI 1.32, 10.54). 1-year OS rate was 75% vs. 25%, respectively (p=.04). Conclusion: HCT-CI is a valid scoring of pre-transplant comorbidities that predicted mortality after AHCT for pts with lymphoma. The physiologic burden of comorbidities is likely to impact the tolerance to AHCT or to other therapies administered upon relapse after transplant. HCT-CI can serve as important tool for both the transplant administrator when planning for resources allocation and clinical trials, and for pts during pre-transplant evaluation and counseling. No significant financial relationships to disclose.
Abstract 15112: Microfluidic Single Cell Analysis Shows Porcine Induced Pluripotent Stem Cell-Derived Endothelial Cells Improve Myocardial Function by Paracrine Activation
Authors: Mingxia Gu, Patricia Nguyen, Shijun Hu, Jordan R Plews, Andrew S Lee, Bruno C Huber, Won Hee Lee, Yongquan Gong, Patricia E Almeida, Andrew Connolly, Robert C Robbins, Michael T Longaker, Joseph C Wu
Journal: Circulation (2012)

Background: Induced pluripotent stem cells (iPSCs) hold great promise for the development of patient-specific therapies for cardiovascular disease. However, clinical translation will require preclinical optimization and validation of large animal iPSC models. Methods and Results: Porcine adipose stromal cells (pASCs) harvested from 5 Yucatan miniswine were reprogrammed using lentivirus carrying Oct4, Sox2, Klf4, and cMyc at a 4:2:2:1 ratio to generate porcine iPSCs (piPSCs). Immunohistochemistry, quantitative PCR, microarray hybridization, and in vivo angiogenic assays confirmed that piPSC-derived endothelial cells (piPSC-ECs) shared similar morphological and functional properties as endothelial cells isolated from the autologous pig aorta (pAorta-ECs). To demonstrate therapeutic potential of these cells, piPSC-ECs were transplanted into mice with myocardial infarction (n=80). Compared to control, animals transplanted with piPSC-ECs showed significant functional improvement on echocardiography (fractional...
Abstract 9326: Peri-Operative Myocardial Damage in Higher-Risk Patients Undergoing Elective Non-Cardiac Surgery
Authors: Richard F Alcock, Dorothy Kouzios, Graham Hillis, David Brieger
Journal: Circulation (2011)

Introduction: The development of high-sensitivity assays has greatly improved the analytical performance of cardiac troponin, allowing detection of very minor damage to cardiac muscle. High sensitivity troponin (hsTnT) is elevated in subgroups of stable populations, with prognostic significance. We postulated hsTnT would be elevated in a proportion of patients undergoing elective non-cardiac surgery, with this elevation predicting adverse peri-operative events. Aims: The aims of our study were to identify the incidence of elevated hsTnT in patients undergoing non-cardiac surgery, and to determine the association between elevated pre-operative hsTnT and adverse peri-operative events. Methods: Consecutive patients aged ≥45 years undergoing major elective non-cardiac surgery, prescribed anti-platelet therapy for primary or secondary cardiovascular event prevention, were included. Baseline, 24 and 48-hour post-operative hsTnT (Roche Diagnostics, 99th percentile 13ng/L) were collected, an elevation above the 99th percentile or if baseline hsTnT elevated, a delta value of 30%, used to define myocardial damage. Results: Included in the analysis were 160 consecutive patients undergoing elective non-cardiac surgery (mean age 72.3 ± 9.7 years, 66% male). Baseline hsTnT was elevated in 29.5% of all patients. Peri-operative myocardial damage occurred in 28.6% of patients. Independent predictors of peri-operative myocardial damage included age (HR 1.07, 1.02-1.12), intra-operative hypotension (HR 3.65, 1.34-9.91), and pre-operative haemoglobin (Hb) concentration (HR 0.97, 0.95-0.99). Baseline elevated hsTnT did not predict peri-operative myocardial damage. Myocardial infarction as defined by the Universal Definition occurred in only 2.7% of patients. Conclusions: Although pre-operative hsTnT was commonly elevated in this cohort, there was no significant association with post-operative myocardial damage. We found 28% of stable higher-risk patients undergoing elective non-cardiac surgery have hsTnT determined peri-operative myocardial damage. The significant associations of intra-operative hypotension and pre-operative Hb concentration suggest myocardial damage is predominantly due to a supply and demand mismatch.
Antagonists of growth hormone-releasing hormone potentiate radiation response in prostate cancer.
Authors: M. Abdel-Wahab, A. Schally, F. Rick, L. Szalontay, J. Varga, Y. Shi, M. Zarandi, A. Pollack
Journal: Journal of Clinical Oncology (2010)

10597 Background: Knockdown of GHRH gene expression suppresses the proliferation of cancer cell lines and antagonists of GHRH (GHRH-A) inhibit growth of experimental human cancer. The effect of GHRH antagonists on radiation response is not completely elucidated. Therefore, experiments of GHRH antagonists (JMR-132 and MIA-606) given after tumor radiation were conducted. Methods: Two experiments involving athymic nu/nu nude mice implanted with PC-3 human tumor xenografts were done. In the first experiment 40 mice (10 animals in each group) were treated as follows: Group 1 control group (no treatment), Group 2 JMR-132 alone, Group 3 radiation (XRT) alone, and Group 4 XRT followed by JMR-132 for 3 weeks (XRT-JMR-132). JMR-132 was injected s.c. at 10 μg/day s.c. daily for 3 weeks. The radiation dose was 8 Gy in a single fraction. In the second experiment 36 nude mice were divided into 4 groups as follows: Group 1 control group (no treatment), Group 2 MIA-606 alone, Group 3 radiation alone (XRT) and Group 4 XRT followed by MIA-606 (XRT-MIA-606). MIA-606 was injected s.c. at 2 μg/day daily for 4 weeks. The radiation dose was a single fraction of 2 Gy. In both experiments, the implanted tumor was exposed to the x-ray beam and the rest of the animal's body was shielded by a lead block. Results: No significant differences were seen when GHRH-A JMR-132 was added after radiation. However, the use of new, more potent GHRH antagonist MIA-606 resulted in a significant potentiation of the inhibitory effect of radiation on the PC3 human prostate cancer. At 4 weeks, an 83% tumor growth inhibition was seen when MIA-606 was given after radiation as compared to a 70% inhibition when radiation was given alone (p < 0.05). MIA-606 alone led to a 39% tumor growth inhibition at 4 weeks compared to control. Conclusions: These results indicate, for the first time, that GHRH antagonists given after radiation may potentiate the inhibitory effect of radiation on tumors. This finding has significant clinical implications for determining the optimal sequence of these drugs with radiation. No significant financial relationships to disclose.
Paediatric respiratory syncytial virus infections: rates and risk factors for hospitalisation
Authors: R Ahmed
Journal: Thorax (2009)

This population-based prospective study set out to establish the rates of respiratory syncytial virus (RSV)-associated paediatric respiratory tract infections in both inpatient and outpatient settings. Cases were identified through the New Vaccine Surveillance Network, a Centre for Disease Control initiative to survey acute respiratory infections in children aged <5 years in three …