tbuckley/cabot-search huggingface dataset:
Abstract 17151: Selective Stimulation of Renal Sympathetic Nerves Increases Stellate Ganglion Nerve Activity and Ventricular Arrhythmias After Myocardial Infarction in Canine
Authors: Bing Huang, Lilei Yu, Zhibing Lu, Bo He, Wenbo He, Jinbo Zhao, Songyun Wang, Kang Yang, Kai Liao, Gaowa Saren, Hong Jiang
Journal: Circulation (2013)

Backgroud: Renal sympathetic nerves (RSN) play a key role in conditions associated with systemic sympathetic hyperactivity. Cardiac sympathetic nerve (especially the left stellate ganglion (LSG)) o...
The effect of bevacizumab plus chemotherapy on the immunological profile of advanced colorectal cancer patients
Authors: B. Rovati, M. Manzoni, K. Bencardino, M. Ronzoni, S. Mariucci, F. Loupakis, E. Gattoni, E. Villa, A. Falcone, M. Danova
Journal: Journal of Clinical Oncology (2008)

14579 Background: A complex cross-talk was discovered between the immunesystem and the endothelial cell compartment during the process of neovascularization in tumors. Several angiogenic mediators, such as the vascular endothelial growth factor (VEGF), have a negative impact on the dendritic cell profile, facilitating the tumor escape phenomenon. Bevacizumab (the humanized monoclonal antibody against VEGF), was found to improve the in vivo T-cell mediated response in metastatic colorectal cancer (mCRC) (Manzoni M, ECCO 2007). We now have focused on the prospective modification of the immunological and the circulating dendritic cell profile during a multicyclic, Bevacizumab-based, first-line treatment for mCRC. Methods: From January to November 2007, we have performed multiparameter flow cytometric analysis of different PB lymphocyte and circulating DC subsets in 29 pts (M/F:19/10, median age:61 yrs; range 32–75) before and every 3 courses of 5FU ± CPT11 + Bevacizumab. Data from a group of 50 healthy subjects (M/F: 25/25, median age: 43; range 21–65) were utilized as control. Results: At baseline, a significant decrease of absolute lymphocyte count, CD4, CD8, CD45RO, CD45RA T-lymphocytes, CD19, CD20 and CD23 B-lymphocytes and NK cells was evidenced in mCRC pts with respect to normal donors, while the DC profile was not substantially different. From the 3rd course of therapy, we showed a trend toward the increase of CD4, CD8 T-lymphocytes and NK cells, together with a decrease of B-lymphocyte subpopulations. After an initial decrease of the DCs and their subsets with respect to the baseline values, a trend toward a progressive increase of the DC pool was evidenced after the 6th and the 9th course. Conclusions: The dynamic modifications of the circulating DCs and of their subsets (that showed a progressive, significant recovery with respect to the baseline picture), together with the significant improvement of the T-cell and NK compartments, indicate that the addition of Bevacizumab to the conventional treatment is able to counteract the negative impact of the standard CT on the immunesystem of advanced cancer patients. No significant financial relationships to disclose.
First-Line Afatinib versus Chemotherapy in Patients with Non–Small Cell Lung Cancer and Common Epidermal Growth Factor Receptor Gene Mutations and Brain Metastases
Authors: Martin Schuler, Yi-Long Wu, Vera Hirsh, Kenneth O’Byrne, Nobuyuki Yamamoto, Tony Mok, Sanjay Popat, Lecia V. Sequist, Dan Massey, Victoria Zazulina, James C.-H. Yang
Journal: Journal of Thoracic Oncology (2016)

Metastatic spread to the brain is common in patients with non-small cell lung cancer (NSCLC), but these patients are generally excluded from prospective clinical trials. The studies, phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations (LUX-Lung 3) and a randomized, open-label, phase III study of BIBW 2992 versus chemotherapy as first-line treatment for patients with stage IIIB or IV adenocarcinoma of the lung harbouring an EGFR activating mutation (LUX-Lung 6) investigated first-line afatinib versus platinum-based chemotherapy in epidermal growth factor receptor gene (EGFR) mutation-positive patients with NSCLC and included patients with brain metastases; prespecified subgroup analyses are assessed in this article.For both LUX-Lung 3 and LUX-Lung 6, prespecified subgroup analyses of progression-free survival (PFS), overall survival, and objective response rate were undertaken in patients with asymptomatic brain metastases at baseline (n = 35 and n = 46, respectively). Post hoc analyses of clinical outcomes was undertaken in the combined data set (n = 81).In both studies, there was a trend toward improved PFS with afatinib versus chemotherapy in patients with brain metastases (LUX-Lung 3: 11.1 versus 5.4 months, hazard ratio [HR] = 0.54, p = 0.1378; LUX-Lung 6: 8.2 versus 4.7 months, HR = 0.47, p = 0.1060). The magnitude of PFS improvement with afatinib was similar to that observed in patients without brain metastases. In combined analysis, PFS was significantly improved with afatinib versus with chemotherapy in patients with brain metastases (8.2 versus 5.4 months; HR, 0.50; p = 0.0297). Afatinib significantly improved the objective response rate versus chemotherapy in patients with brain metastases. Safety findings were consistent with previous reports.These findings lend support to the clinical activity of afatinib in EGFR mutation-positive patients with NSCLC and asymptomatic brain metastases.
Political homogeneity can nurture threats to research validity
Authors: John R Chambers, Barry R Schlenker
Journal: Behavioral and Brain Sciences (2015)

Abstract Political homogeneity within a scientific field nurtures threats to the validity of many research conclusions by allowing ideologically compatible values to influence interpretations, by minimizing skepticism, and by creating premature consensus. Although validity threats can crop in any research, the usual corrective activities in science are more likely to be minimized and delayed.
Synergistic interaction between rituximab and 2-chlorodeoxyadenosine (2-CdA) against Waldenstrom's Macroglobulinemia preclinical model
Authors: A. M. Al-Katib, A. Aboukameel, F. Beck, R. Mohammad
Journal: Journal of Clinical Oncology (2004)

2529 Background: Waldenstrom's Macroglobulinemia (WM) is an incurable malignant disorder. Rituximab represents a new therapeutic modality for B-cell tumors and has modest activity in WM. Among cytotoxic agents, 2-CdA has significant activity. In this study, Rituximab and 2-CdA combination was used in pre-clinical SCID mouse xenograft model of human WM (WSU-WM-SCID) (Blood 81:3034, 93). Methods: Subcutaneous (sc) tumor-bearing ICR-SCID mice were randomly assigned to one of four groups (8 animals each): Group 1 (control); Group 2 received Rituximab intravenously (iv) via tail vein daily x 5 days at a dose of 150 mg/kgm/day; Group 3 received 2-CdA injections sc daily x 5 days at MTD of 30 mg/kg/d; Group 4 received a combination of Rituximab and 2-CdA, as in groups 2 and 3, concurrently. Two treatment cycles were given with one week rest in between. Subsequent experiments focused on biological studies and involved removing tumors following therapy for flow cytometry and deoxycytidine kinase (dCK) activity. Results: Both agents showed modest activity in this model [Rituximab T/C = 30%, T-C = 13 days, Log10kill 1.9; 2CdA T/C = 36.9%, T-C = 14 days, Log10kill 1.33] but tumors progressed within 1 week. Residual tumors following Rituximab therapy preserved original phenotype except were CD20(-) due to Rituximab binding as confirmed by anti-Rituximab antibody. When used in combination, 8/8 animals were cured (no tumor development for 120 days). Treatment was well tolerated. Rituximab therapy increased dCK activity by 170%, 210%, and 258% after 1, 3, and 5 injections respectively. dCK is key to the phosphorylation of 2-CdA to its active metabolite 2-CdATP. Conclusions: there is synergistic interaction between Rituximab and 2-CdA leading to cure in this WM model. Enhancing dCK activity is one mechanism of interaction between the two agents. The WSU-WM-SCID is a model of resistant WM where no cures were achieved using standard agents until now. Clinical use of the combination against WM is recommended. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration International Waldenstrom's Macroglobulinemia Foundation
Effect of Inhaled Triamcinolone on the Decline in Pulmonary Function in Chronic Obstructive Pulmonary Disease
Authors: The Lung Health Study Research Group
Journal: New England Journal of Medicine (2000)

Chronic obstructive pulmonary disease (COPD) results from a progressive decline in lung function, which is thought to be the consequence of airway inflammation. We hypothesized that antiinflammatory therapy with inhaled corticosteroids would slow this decline.
Variations in the Cell Cycle During Azo Dye Hepatocarcinogenesis&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: A. Simard, G. Cousineau, R. Daoust
Journal: JNCI Journal of the National Cancer Institute (1968)

Radioautographic and cytophotometric studies were undertaken to determine whether variations in the duration of the G2 phase of the cell cycle occur in rat hepatocytes during 4-dimethylaminoazobenzene (DAB) carcinogenesis. In hepatic nodules of DAB-fed rats, a decrease in the number of labeled mitoses was accompanied by an increase in the level of ploidy, indicating a delay or an arrest of cells in the G2 phase of the cell cycle. In hyperbasophilic foci considered as the sites of neoplastic transformation, higher percentages of labeled mitoses were obtained and ploidy was reduced, indicating a shortening of the G2 phase. Thus it seems that neoplastic transformation is associated with an elimination or inhibition of both the G1 and G2 blocks of the cell cycle. Both changes contribute to the acceleration of cell proliferation in sites of tumor formation.
제10차 춘계 학술대회 초록집 : 총회구연 9 ; 말디토프 질량분석을 이용한 한국인의 B형 간염 바이러스의 유전자형 및 임상적 의의에 대한 재평가
Authors: 이중민, 안상훈, 장혜영, 신지은, 홍선표, 김수옥, 한광협, 전재윤, 문영명
Journal: Clinical and Molecular Hepatology (2004)
Weekly docetaxel rechallenge in patients with hormone-resistant prostate cancer refractory to conventionally three weekly docetaxel.
Authors: S. Fuxius, A. Mueller, K. Kleitz, M. Schuetz, Ch. Philipps, P. Buvari, A. Karcher
Journal: Journal of Clinical Oncology (2010)

e15004 Background: The common standard treatment for hormone resistant prostate cancer is a 3-weekly (q3w) schedule with prednisone 10 mg qd and docetaxel 75 mg/m2 q3w. In case of progression almost 2/3 of patients profit from a docetaxel rechallenge. If the PSA rises again therapy is usually discontinued. Methods: We identified 31 out of 106 patients retrospectively (Jun 2004-Oct 2009) who were reportedly refractory to the q3w schedule and were continued on a weekly (q1w) schedule of prednisone 10 mg qd and docetaxel 30 mg/m2 q1w. 5 patients never responded to q3w, 25 patients responded initially to q3w but then became progressive, 1 patient showed a PSA decline to q3w but was regarded as clinically progressive. Median time to PSA nadir under q3w schedule was 12 weeks. Average age was 71 years and median q3w treatment of docetaxel was 16 weeks. Median baseline PSA was 96 ng/ml. Under the q3w schedule median PSA decline was about 43%. Results: Surprisingly 80% (25/31) of the q3w pretreated patients showed a remarkable median PSA decline of 46% to q1w treatment. Only 6 patients showed PSA progression. Median treatment duration of q1w was 16 weeks. Median time to PSA nadir was 13 weeks and median PSA at the time of rechallenge was 112 ng/ml. PSA response greater than 50% was reached in 45% (14) of patients in the q3w schedule and in 39% (12) of patients in the q1w schedule. Dose intensity of both schedules was comparable (q3w: 28mg/m2, q1w: 27mg/m2). Toxicity profile changed slightly (more nail problems and PNP in q1w) but the q1w schedule was generally well tolerated. Median overall treatment duration was 16 weeks for both schedules. Conclusions: This retrospectively analysed data should be controlled prospectively but until further data is available we suggest a rechallenge with a q1w schedule of docetaxel in all patients refractory to a q3w schedule before discontinuing the drug, notably also for primary nonresponder to the q3w schedule. No significant financial relationships to disclose.
EGFR mutations and human papillomavirus in squamous cell carcinoma of tongue and tonsil
Authors: I. Na, H. Kang, Y. Park, J. Koh, S. Cho, B. Lee, Y. Lee, Y. Shim, B. Ryoo, S. Yang
Journal: Journal of Clinical Oncology (2006)

10027 Background: Some studies reported the presence of somatic mutation of EGFR in head and neck cancer. Human papillomavirus (HPV) was associated with some types of head and neck cancer. We performed this study to determine clinical significance of EGFR mutation and its association with HPV infection in patients with tongue and tonsil cancer. Methods: We sequenced exons 18–21 of EGFR TK domain and HPV typing was performed using the HPV DNA chip in tissues of patients with tongue and tonsil cancer. Univariate and multivariate analysis was performed. Results: Eighty-one patients were included. We detected EGFR mutation in 10 (12%) patients. Mutation was significantly frequent in never-smoker (21% versus 5%; P = 0.031). The mutation frequency did not differ between tongue and tonsil cancer (12% vs. 13%, respectively; P = 0.978). There was no difference between female and male (12% vs. 14%, respectively; P = 0.754). Eleven of 81 (14%) patients were HPV positive. HPV positivity was more common in young (&lt;60 years) than older (≥60 years) patients (20% vs. 3%, respectively; P = 0.039). Patients with tonsil cancer showed more frequent HPV positivity than tongue cancer (42% vs. 2%, respectively; P &lt; 0.001). There was no association between HPV positivity and EGFR mutation. In terms of disease-free survival, patients with EGFR mutation had better survival independently of stage and primary site (hazard ratio, 0.246; 95% CI, 0.075 to 0.802). Conclusions: We did not find association between EGFR mutation and HPV positivity. Patients with EGFR mutation showed better outcome in tongue and tonsil cancer. These results suggest that EGFR mutation may be a prognostic factor in patients with head and neck cancer. No significant financial relationships to disclose.
Is prostate-specific antigen progression a surrogate for objective clinical progression in early prostate cancer?
Authors: D. Newling, K. Carroll, T. Morris
Journal: Journal of Clinical Oncology (2004)

4652 Background: It is a common misconception that a correlation between endpoints is enough to demonstrate surrogacy. To show true surrogacy, the effect of an intervention on an intermediate endpoint relative to a control treatment needs to reliably predict the effect of the intervention on the clinical outcome of interest. Valid surrogate endpoints are needed to accelerate availability of information about new therapies for early prostate cancer where clinical progression and survival times are prolonged. The usefulness of prostate-specific antigen (PSA) progression as a surrogate for objective clinical progression has therefore been assessed in the bicalutamide (‘Casodex’) Early Prostate Cancer (EPC) Program, the world's largest prostate cancer treatment program. Methods: Individual data from all 8113 patients across 21 countries in the EPC Program were examined. Time to PSA progression and time to objective clinical progression were the endpoints evaluated. The effect of treatment on time to PSA progression was compared with the effect of treatment on time to objective clinical progression. Results: Analyses suggest that time to PSA progression is a modest surrogate endpoint for the effect of a hormonal intervention on objectively confirmed progression in patients with early prostate cancer (r2 = 0.52–0.65, p<0.001). An intervention that produces around a 50% reduction in the risk of PSA progression would likely result in around a 20% reduction in the risk of objective clinical progression. Conclusions: The effect of treatment on PSA progression is moderately predictive for the effect of hormonal treatment on objective clinical progression. A large effect on PSA progression predicts for a smaller, but nonetheless clinically important effect on objective clinical progression. These data suggest that a large positive treatment effect on time to PSA progression is reasonably likely to reflect a clinically important delay in objective clinical progression, making PSA progression a valid endpoint for the evaluation of hormonal medicines in early prostate cancer. ‘Casodex’ is a trademark of the AstraZeneca group of companies. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca AstraZeneca AstraZeneca
Prognostic value of PS2 and cathepsin D in 710 human primary breast tumors: multivariate analysis.
Authors: J A Foekens, W L van Putten, H Portengen, H Y de Koning, B Thirion, J Alexieva-Figusch, J G Klijn
Journal: Journal of Clinical Oncology (1993)

Evaluation of the prognostic value of cytosolic PS2 (pS2 protein) and cathepsin D in a large series of breast cancer patients by multivariate analysis taking into account steroid receptors and conventional prognostic factors.Prognostic factors were analyzed in 710 primary breast cancers (median follow-up, 4 years). PS2 and cathepsin D were measured by radiometric immunoassays. Estrogen receptor (ER) and progesterone receptor (PgR) status were assessed by radioligand binding assays and multiple-point Scatchard analysis.The best cutoff point for PS2 to discriminate between positive (61% of the tumors) and negative was 2 ng/mg protein (univariate P value in 5-year relapse-free survival = .003). For cathepsin D, no sensible cutoff point could be chosen, since there was a continuous association between the level of cathepsin D and relapse rate (P = .001). In Cox multivariate analysis, relapse rate decreased with age of premenopausal/perimenopausal patients and with PS2 or steroid receptor positivity, and increased with the size of the tumor, the number of positive lymph nodes, and increasing levels of cathepsin D. In analysis for overall survival, age of both premenopausal/perimenopausal and postmenopausal patients, tumor size, the number of positive lymph nodes, ER/PgR, and PS2 were all independently associated with the rate of death. The level of cathepsin D was positively correlated with the rate of death, but this trend was not statistically significant. Separate Cox multivariate analyses for relapse-free survival in subgroups of patients as defined by nodal status showed that the contribution of PS2 and cathepsin D was the strongest in the node-negative subgroup. Node-negative patients with tumors containing PS2 values < or = 2 ng/mg protein and cathepsin D values more than 70 pmol/mg protein experienced a 4.5-fold increase in relapse rate as compared with those with PS2 levels greater than 2 ng/mg protein and cathepsin D levels < or = 30 pmol/mg protein.PS2 and cathepsin D are independent prognostic factors in primary breast cancer and lymph node-negative patients.
Autologous and Homologous Implantation of Human Cells Transformed &lt;italic&gt;In Vitro&lt;/italic&gt; by Simian Virus 40&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Jensen, Fred, Koprowski, Hilary, Pagano, Joseph S., Pontén, Jan, Ravdin, Robert G.
Journal: JNCI Journal of the National Cancer Institute (1964)

Journal Article Autologous and Homologous Implantation of Human Cells Transformed In Vitro by Simian Virus 40 Get access Fred Jensen, Fred Jensen The Wistar Institute, Philadelphia, Pennsylvania Search for other works by this author on: Oxford Academic PubMed Google Scholar Hilary Koprowski, Hilary Koprowski The Wistar Institute, Philadelphia, Pennsylvania Search for other works by this author on: Oxford Academic PubMed Google Scholar Joseph S. Pagano, Joseph S. Pagano The Wistar Institute, Philadelphia, Pennsylvania Search for other works by this author on: Oxford Academic PubMed Google Scholar Jan Pontén, Jan Pontén The Wistar Institute, Philadelphia, Pennsylvania Search for other works by this author on: Oxford Academic PubMed Google Scholar Robert G. Ravdin Robert G. Ravdin The Wistar Institute, Philadelphia, Pennsylvania Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 32, Issue 4, April 1964, Pages 917–937, https://doi.org/10.1093/jnci/32.4.917 Published: 01 April 1964 Article history Received: 26 September 1963 Published: 01 April 1964
Capecitabine (XEL) plus oxaliplatin (OX) tailored regimen for the first-line treatment of elderly patients (pts) with metastatic colorectal cancer (MCC). Final results of the Southern Italy Cooperative Oncology Group (SICOG) trial 0108
Authors: F. Buzzi, D. Natale, A. Farris, A. Gambardella, L. Maiorino, S. Tafuto, V. Lorusso, S. Leo, M. Cannone, P. Comella
Journal: Journal of Clinical Oncology (2005)

3582 Background: In pts with MCC, XEL has shown greater response rate (RR), equivalent progression-free (PFS) and overall survival (OS), and better tolerability profile compared with 5-fluorouracil/leucovorin (5FU/LV). The addition of OX to 5FU/LV (FOLFOX4) has been shown to improve RR and PFS versus 5FU/LV, and RR, PFS and OS compared with irinotecan plus 5FU/LV. XEL may be an effective, well tolerated and more convenient alternative to 5-FU/LV in combination with these agents, namely in older pts. Methods: Elderly (≥ 70 years) pts with MCC were treated every 3 weeks with XEL 1,000 mg/m2 orally twice daily on days 1 to14, and OX 85 mg/m2 i.v. on day 1 (XELOX regimen). In the absence of grade (G) ≥ 2 hematologic toxicity, OX was increased to 100 mg/m2 in the 2nd cycle, and in the absence of G ≥ 2 non-hematologic toxicity during cycle 2, XEL was increased to 1,250 mg/m2 twice daily in 3rd and subsequent cycles. After treating 35 pts (1st series), protocol was amended so that only OX was planned to be raised to 100 mg/m2 and 130 mg/m2 in 2nd and 3rd cycle, respectively, in the following 45 pts (2nd series) Results: 76 pts, median age 75 (range 70–82) years entered into this study. In the 1st series, OX dose was increased in 2nd cycle in 18 (51%) pts, and XEL dose was increased in 3rd cycle in 4 (11%) pts. In the 2nd series, OX dose was increased to 110 mg/m2 in 2nd cycle in 26 (63%) pts, and to 130 mg/m2 in the 3rd cycle in 19 (46%) pts. In all, 2 complete and 29 partial responses were observed, for an overall RR of 41% (95% CI, 30–53%). After a median follow-up of 21 months (range, 6–36), median PFS was 8.5 months (95% CI, 6.7–10.3 months), and the median OS was 14.4 (95% CI, 11.9–16.9) months. On the whole series, 4 (5%) pts showed G ≥ 3 hematologic toxicity during their treatment, peripheral neuropathy reached G 3 in 6 (8%) pts, and G 3 hand-foot syndrome was seen in 10 (13%) pts. Conclusions: Fit elderly pts with MCC show a good RR to standard-dose XELOX with only mild toxicity observed in most pts. XELOX should therefore be considered as an important therapeutic option for elderly pts with MCC. No significant financial relationships to disclose.