tbuckley/cabot-search huggingface dataset:
Role of JunD in androgen induction of oxidative stress in androgen-dependent human prostate cancer cells and in mouse prostate
Authors: Farideh Mehraein-Ghomi, Elyse Lee, Dawn Church, Marie Kegel, Hirak Basu, George Wilding
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

119 

The role of androgen in prostate cancer development is well established. It has also been shown from our and other laboratories that androgen induces Reactive Oxygen Species (ROS) production in androgen-dependent LNCaP human prostate carcinoma cells. However, the androgen receptor signaling pathways associated with androgen-induced ROS production in prostate cancer is not well understood. We have previously shown that JunD, a prominent member of redox-sensitive transcription factors AP-1 complex is involved in the androgen induction of ROS production in LNCaP cells.

Based on siRNA technology we developed a stable LNCaP cell line. A clone with 81% reduction in JunD expression was used for further studies. In the presence of 0.01,0.1, 1 and 10nM R1881 we did not observe a significant increase in ROS production by this clone. We have also shown that constitutive overexpression of JunD causes 51% increase in the accumulation of ROS in LNCaP cells in the presence of 5% FBS.

From these data, we conclude that JunD is a key mediator in androgen induction of ROS in human prostate cancer cells. In order to investigate the role of JunD in normal prostate and prostate cancer development, we have now devloped a transgenic mouse model that specifically overexpresses JunD in the prostate gland. The details of the development and characterization of this transgenic animal model and the level of oxidative stress in its prostate gland and other organs will be presented.
Comparison of outpatient parenteral nutrition regimens of patients with GIT tumors with and without receiving simultaneous palliative systemic chemotherapy
Authors: P. Stuebs, J. Fahlke, C. Schmidt, P. Habermann, A. Hribaschek, K. Ridwelski, H. Lippert
Journal: Journal of Clinical Oncology (2006)

18578 Background: The nutritional status of oncology patients significantly impacts the success of tumor-specific therapy.This study was designed to objectify the benefit of parenteral nutrition therapy (PN) administered in the ambulatory care setting and at home by evaluation of nutritional parameters in patients simultaneously undergoing palliative systemic chemotherapy. Methods: From 2003 through 2005 56 patients diagnosed with metastatic GIT tumors were included in the survey.43 patients received PN at home (hPN n=16) or in the ambulatory clinic (aPN n= 27) over a period of 8 weeks because of their poor nutritional status.Of 36 patients who underwent palliative systemic chemotherapy, 25 received PN (13 hPN/12 aPN).In aPN 600kcl were administered, while 1500 kcal where given in hPN.The therapy was administered 5 times a week.In all patients albumin and total protein were measured weekly along with body composition via bioelectric impedance analysis (BIA). Results: Over the course of 8 weeks a continuous decrease of albumin and total protein was found in patients not receiving PN.In aPN laboratory values decreased during the first 4 weeks and later stabilized at low levels.In hPN continuous increases in albumin and total protein were observed.BIA results were comparable.In patients receiving chemotherapy without PN there was an initial improvement of relevant BIA parameters followed by a noticeable decline, while in patients receiving chemotherapy and simultaneous PN a stabilization of values occurred after a slight initial decrease.Evaluation of the corresponding laboratory values showed no decline in the group receiving PN but a significant decline in patients receiving chemotherapy only. Conclusions: The nutritional status of patients with GIT tumors shows a continuous decline during chemotherapy without the addition of PN.This study’s data indicate an advantage of PN for patients with GIT tumors, when started early enough. When chemotherapy and PN are administered, there are limitations the use of BIA as a method of measurement.Verification of laboratory parameters specific to nutrition in the process of treatment is both adequate and necessary for assessment of nutritional status. No significant financial relationships to disclose.
Mantle cell lymphoma.
Authors: N L Harris
Journal: Journal of Clinical Oncology (1994)

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.1994.12.4.876 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 8151331 Mantle cell lymphoma. N L HarrisxN L HarrisSearch for articles by this author https://doi.org/10.1200/JCO.1994.12.4.876 PDF "Mantle cell lymphoma.." Journal of Clinical Oncology, 12(4), pp. 876–877© 1994 by American Society of Clinical Oncology
Systematic evaluation of the impact of disease progression (DP) date determination on progression-free survival (PFS) in advanced lung cancer: A joint North Central Cancer Treatment Group (NCCTG) and Southwest Oncology Group (SWOG) investigation.
Authors: S. J. Mandrekar, Y. Qi, K. Allen-Ziegler, S. L. Hillman, M. W. Redman, S. E. Schild, D. R. Gandara, A. A. Adjei
Journal: Journal of Clinical Oncology (2011)

7005 Background: In advanced lung cancer, overall survival is largely influenced by the DP status. At ASCO 2010, we reported that the PFS estimates are significantly impacted by the approach used for declaring DP date; the magnitude of difference being large enough to alter trial conclusions. Here, we present updated results from NCCTG and further validate our findings using data from SWOG. Methods: Individual patient (pt) data from 14 NCCTG and 7 SWOG trials were used. Reported progression date (RPD) was either the scan date or the clinical deterioration date. DP date was determined using one of the 4 common methods (M): RPD (M1), one day after last progression-free (PF) scan (M2), midpoint between last PF scan and RPD (M3), or interval censoring (M4). PFS was defined as the earlier of the time to DP or death from any cause, and estimated using the method of Kaplan-Meier (M1-3) or maximum likelihood (M4). Results: Within NCCTG (SWOG), 67% (78%) of pts reported DP during treatment, 11% (24%) of pts died without DP, and the median time from the last PF scan to DP during treatment and follow-up was 1.4 (1.3) mos, and 3.0 (1.7) mos respectively, for NSCLC. Results were similar for SCLC trials. PFS estimates using RPD was the highest, with method 2 being the most conservative. M3 and M4 were similar since majority of DP occurred during treatment (frequent disease assessments). For the 3 randomized trials, the 4 methods resulted in the same overall conclusion. Conclusions: Although NCCTG and SWOG had different data collection requirements for monitoring DP, the results are consistent with % difference in PFS estimates being large enough to conclude efficacy in advanced lung cancer. Thus, standards for declaring DP date and sensitivity analysis when analyzing PFS data are critical when reporting efficacy or comparing trial results. DP date method Median PFS (mos) NSCLC SCLC NCCTG (n=660) SWOG (n=297) NCCTG (n=116) SWOG (n=131) 1 4.3 3.1 2.7 1.3 2 1.8 1.5 0.03 0.03 3 3.3 2.2 1.8 0.7 4 (lower, upper) 3.52, 3.55 2.86, 2.89 1.45, 1.48 0.03, 0.16 % Difference Method 1 vs. 2 Method 1 vs. 3 58% 23% 52% 29% 99% 33% 98% 46%
Final results of a phase II study of liposomal cisplatin -vinorelbine combination as first-line treatment in HER2/neu negative metastatic breast cancer.
Authors: F. S. Farhat, S. Temraz, J. G. Kattan, K. Ibrahim, N. Bitar, N. Haddad, H. Hatoum, A. Shamseddine
Journal: Journal of Clinical Oncology (2011)

e11080 Background: Cisplatin-vinorelbine combination recently showed interesting results in the metastatic setting. Nevertheless, the use of cisplatin was limited by the frequently induced vomiting and nephrotoxicity. Liposomal cisplatin (Lipoplatin) is a non-toxic alternative agent to cisplatin. The aim of this study is to evaluate the efficacy and safety of liposomal cisplatin-vinorelbine combination in first line metastatic breast cancer (MBC) patients (pts). Methods: From Aug 2007 to July 2009, 35 pts with MBC and no prior treatment for their metastatic disease, PS 0-2, HER2/neu negative and at least one measurable lesion were enrolled. Treatment included I.V. vinorelbine 30 mg/m2 on days 1 & 8 and liposomal cisplatin 120 mg/m2 on days 1, 8 & 15 repeated every 3 weeks for a total of 6 cycles. Primary objectives: objective response rate (ORR), time to treatment failure (TTF) & time to progression (TTP). Results: The median age was 52 years (29-74). 74% of pts had visceral metastases. A total of 174 cycles were administered with a median number of 6 per patient. At the time of the analysis 32 pts were evaluable for response. An ORR was observed in 17 pts (53.1%) & complete response in 3 pts (9.4%). Twelve (37.5%) pts had stable disease. The median TTF & TTP were 7 & 8 months respectively. After a median follow-up of 15.5 months, 18 of the 35 patients treated in the study were still alive and the median survival time was 22 months (95% CI, 14-30). All pts (35) were evaluable for toxicity. No WHO G3-4 nephrotoxicity or neuropathy was noted. G3-4 nausea/vomiting were observed in 5 pts (14.3%). Four pts (11.4%) had G3 asthenia. Four pts (11.4%) had G3 anemia & 25 pts (71.5%) had G3-4 neutropenia. Gr 3-4 neutropenia occurred in 44% of administered cycles with 11.4% episodes of febrile neutropenia. 30% of chemotherapy administrations were delayed due to grade 3-4 neutropenia. No neutropenic death was observed. Conclusions: The new combination of liposomal cisplatin & vinorelbine shows promising activity & good tolerance as first line treatment for HER2/neu negative MBC. These results warrant further investigation of this regimen in phase III trials as first line therapy in patients with MBC.
Anthrax tumor toxin (LeTx) selectively kills B-RAF mutant melanomas
Authors: A. E. Frankel, R. J. Abi-Habib, J. O. Urieto, S. Liu, S. H. Leppla, G. F. van de Woude, N. S. Duesbery
Journal: Journal of Clinical Oncology (2005)

7533 The efficacy of anthrax tumor toxin (LeTx) was tested on a panel of 18 human melanoma cell lines using a 3H-Leucine incorporation inhibition assay. 11/18 cell lines were sensitive to LeTx (IC50 < 350 pM, percent cell kill > 75%), while the remaining 7/18 were not sensitive to LeTx (IC50 > 750 pM, Percent cell kill < 60%). 10/11 sensitive melanoma cell lines carried the V599E BRAF. Only 1/7 resistant cell line was BRAF mutation positive (p < 0.0001). 6/7 resistant cell lines carried the Q61R or Q61K N-Ras mutation. Next, LeTx effects on 3H-Thymidine incorporation were measured. In 11/11 sensitive cell lines, the IC50 for 3H-thymidine incorporation was lower than that of 3H-Leucine incorporation indicating that the majority of surviving cells at maximal concentration were in cell cycle arrest. 4/7 cell lines that were not sensitive to LeTx by 3H-Leucine incorporation had low IC50 values in the 3H-Thymidine incorporation inhibition assay (IC50 < 275 pM) and a significantly lower percentage of 3H-thymidine uptake at maximum concentration suggesting significant tumor cell growth arrest rather than tumor cell death. Anthrax toxin receptor (ATR) levels, measured by saturation assay with 125I-PA, varied between 3562 and 32440 receptors/cell with resistant cell lines having the same levels of ATR expression as sensitive cell lines and no correlation of ATR receptor levels with IC50 for LeTx sensitive cell lines. Total and phosphorylated levels of MEK1/2 and ERK1/2 in the cell lines were quantified by western blots and densitometry. LeTx killing correlated with MEK1/2 activation levels. 9/11 sensitive melanoma cell lines and 2/7 resistant melanoma cell lines had a P-MEK1/2 to MEK1/2 ratio > 0.3 (p < 0.001). P-ERK1/2 to ERK1/2 levels did not correlate with melanoma cell line sensitivity to LeTx. The small molecular weight MEK1/2 inhibitor U0126 was tested for effects on the cell lines. 6/6 LeTx resistant cells were resistant to U0126; 5/9 LeTx sensitive cells were sensitive to U0126. In summary, melanoma cell line LeTx sensitivity correlated with B-Raf mutation, P-MEK1/2 levels, and U0126 sensitivity, but not ATR or P-ERK1/2. In future clinical trials of LeTx in metastatic melanoma, these results may provide molecular targets to identify responders. No significant financial relationships to disclose.
Elevated Systolic Blood Pressure as a Predictor of Long-Term Cancer Mortality: Analysis by Site and Histologic Subtype in 10,000 Middle-Aged and Elderly Men&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: U Goldbourt, E Holtzman, S Yaari, L Cohen, L Katz, H N Neufeld
Journal: JNCI Journal of the National Cancer Institute (1986)

The association of a casual reading of blood pressure (BP) in 1963 to subsequent 15-year cancer mortality was examined in a cohort of 10,059 middle-aged and elderly men. Systolic BP (SBP), but not diastolic BP, predicted significantly long-term cancer mortality occurring in 369 subjects. The covariate-adjusted relative risk (RR) estimated by Cox's proportional hazard model was 1.10 [95% confidence interval (CI), 1.00-1.21]. In patients aged less than 60 at the beginning of the study, increased cancer mortality was mainly observed in association with SBP of more than 150 mm Hg. In subjects aged 60 or above, the estimated RR was 1.21 (95% CI, 1.03-1.42). Exclusion of 40 men in whom diagnosis made prior to 1963 or death occurred through 1965 did not alter the results. An excess mortality in men who reported pharmacologic treatment for hypertension while under follow-up was fully accountable by their age, BP, and smoking habits. Analysis by site suggested that the association was mainly due to increased mortality from cancer of the digestive and genitourinary organs (estimated RR's, respectively, 1.20 and 1.26; 95% CI's, respectively, 1.03-1.39 and 0.99-1.59). Analysis by histologic subtype suggests an association with adenocarcinoma (RR = 1.19, 95% CI, 1.04-1.37) but not squamous cell or transitional cell carcinomas, myeloma, lymphomas, and leukemias.
Dose intensity in the treatment of diffuse large-cell lymphoma.
Authors: J R Anderson, M T Santarelli, B Peterson
Journal: Journal of Clinical Oncology (1990)

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.1990.8.11.1927 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 2230883 Dose intensity in the treatment of diffuse large-cell lymphoma. J R AndersonxJ R AndersonSearch for articles by this author , M T SantarellixM T SantarelliSearch for articles by this author , B PetersonxB PetersonSearch for articles by this author https://doi.org/10.1200/JCO.1990.8.11.1927 PDF "Dose intensity in the treatment of diffuse large-cell lymphoma.." Journal of Clinical Oncology, 8(11), pp. 1927–1928© 1990 by American Society of Clinical Oncology
Imiquimod: A TLR-7 agonist as adjuvant for a recombinant protein cancer vaccine
Authors: S. Adams, D. O'Neill, D. Nonaka, O. Manches, L. Chiriboga, K. Siu, Y. Shao, S. Gnjatic, A. Pavlick, N. Bhardwaj
Journal: Journal of Clinical Oncology (2007)

8545 Purpose: This clinical trial evaluates the safety and adjuvant activity of imiquimod, a toll-like receptor (TLR)-7 agonist, when given with a NY-ESO-1 protein vaccine. Imiquimod, by locally activating and recruiting dendritic cells (DCs) into the skin, is expected to stimulate antigen uptake by DCs, induce maturation and migration to draining lymph nodes, and to induce antigen-specific T and B cell immunity. Methods: Pilot study; 9 patients with resected stage 2B-3C malignant melanoma. Four 21 day cycles consisted of topical imiquimod cream (250 mg) on days 1–5 and id. injected NY-ESO-1 protein (100 mcg) into the site on day 3. Blood was drawn at several time points for immune monitoring; skin punch biopsies were obtained from control, imiquimod and vaccination sites 48 hours after the last vaccination. Results: The regimen was tolerated well, all patients completed four vaccinations. AEs were mild and transient and included injection site reactions (8/9 patients), fatigue (4/9 patients) and fever (2/9 patients). Significant levels of antigen-specific CD4+ or CD8+ T cell responses were not detected in ex-vivo ELISPOT assays. However, intracellular cytokine staining assays after in vitro pre-stimulation indicated that 6 of 8 subjects developed NY-ESO-1 CD4+ T cell responses. Humoral immunity was manifest by the induction of anti-NY-ESO-1 antibodies in 7/9 patients post-vaccination. Histochemistry of skin sections showed significant dermal mononuclear cell infiltrates in Imiquimod treated skin, whereas none were seen in untreated skin (p&lt;0.01). IHC revealed markedly increased numbers of CD3+ (T-cells), CD68+ (macrophages/monocytes), CD123+ (plasmacytoid DCs) and DC-LAMP+ (mature myeloid DCs) immune cells in Imiquimod treated skin when compared with control skin of the same patients (p&lt;0.05). Conclusion: Imiquimod, a topical immune response modifier, generated clear inflammatory infiltrates in the dermis, with significant increases in antigen-presenting cells and T cells. Imiquimod was well tolerated when used as an adjuvant to an NY-ESO-1 protein vaccine. Systemic immunity of both humoral and cellular types was induced in the majority of patients; however, responses were weak and the vaccine combination needs to be optimized in future studies. No significant financial relationships to disclose.
Hospital Care Efficiency and the SMART (Specific, Measurable, Agreed, Required, and Timely) Medicine Initiative
Authors: Ronen Zalts, Dana Ben-Hur, Ali Yahia, Jasmin Khateeb, Vera Belsky, Nirit Grushko, Gidon Berger
Journal: JAMA Internal Medicine (2016)

This article describes trends in the use of low-value diagnostic tests at a hospital after implementation of consensus recommendations developed by a team of physicians and engineers to reduce their use.
Characteristic of cytokines levels of blood and sputum in COPD exacerbation
Authors: Sofya Nesterovich, Ekaterina Bukreeva
Journal: European Respiratory Journal (2011)

To study IL-8 and TNF-α levels in blood and sputum in COPD exacerbation in dependence on availability and character of infectional factor.

52 COPD exacerbation patients were examined, infectional nature of exacerbations was proved at 35 patients (first group), infectional factor was not found at 17 patients (second group). The quantitative bacteriological sputum research, definition diagnostic main IgG, IgM levels to Ch.pneumoniae, M.pneumoniae in serum by means of immuno-assay method, in sputum by means of PCR method were made. IL-8, TNF-α levels in sputum and serum were defined by means of hardphase immuno-assay method.

Cytokines levels in the sputum at COPD exacerbation in first group were high than in second group: TNF-α level was 143.1±71.9 pg/ml and 31.0±12.6 pg/ml, (p=0.018), IL-8 level was 1244.5±197.4 pg/ml and 1088.8±222.5 pg/ml, (p=0.021).

Differences of TNF-α level were both in blood and in sputum in dependence on infectional agent species: in sputum its level was high in H.influenzae exacerbation (290.8±54. pg/ml, p=0.017) as compared with S.pneumoniae (110.6±45.9 pg/ml), M.pneumoniae (85.1±37.1 pg/ml), Ch.pneumoniae (132.6±32.1 pg/ml). While in blood TNF-α level was high in M.pneumoniae (887.2±164.2 pg/ml, p=0.019) as compared with S.pneumoniae (102.2±32.1 pg/ml), H.influenzae (182.2±44.9 pg/ml) and Ch.pneumoniae (495.0±118.3 pg/ml).

Il-8 level was different only in blood. Its level was high in H.influenzae exacerbation (112.0±47. pg/ml. p=0.008) as compared with S.pneumoniae (42.0±13.1 pg/ml), M.pneumoniae (36.2±19.5 pg/ml) and Ch.pneumoniae (53.0±37.2 pg/ml).Proinflammatory cytokines (Il-8, TNF-α) levels in sputum and blood were high at infectional COPD exacerbation.
Tumorigenic Nucleic Acid Extracts From Tissues of a Transplantable Carcinoma, Vx7&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Ito, Yohei, Evans, Charles A.
Journal: JNCI Journal of the National Cancer Institute (1965)

Journal Article Tumorigenic Nucleic Acid Extracts From Tissues of a Transplantable Carcinoma, Vx7 Get access Yohei Ito, Yohei Ito Department of Hygiene, Nara Gakugei (National) University, Nara, Japan, and Department of Microbiology, School of Medicine, University of Washington, Seattle, Washington Search for other works by this author on: Oxford Academic PubMed Google Scholar Charles A. Evans Charles A. Evans Department of Hygiene, Nara Gakugei (National) University, Nara, Japan, and Department of Microbiology, School of Medicine, University of Washington, Seattle, Washington Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 34, Issue 3, March 1965, Pages 431–437, https://doi.org/10.1093/jnci/34.3.431 Published: 01 March 1965 Article history Received: 31 August 1964 Published: 01 March 1965
Axillary lymphadenectomy can be safely avoided in patients with breast cancer and negative sentinel lymph node biopsy
Authors: E. Millastre, M. Ruiz-Echarri Sr., M. Ortega, J. I. Mayordomo, R. Lastra, E. Prats, J. Lambea, E. Aguirre, P. Razola, R. Andrés, A. Tres, J. Banzo
Journal: Journal of Clinical Oncology (2006)

10787 Background: Patients with breast cancer in which sentinel lymph node biopsy is histologically negative for tumor cells, have a low probability of having involvement of additional regional lymph nodes. Lymph node dissection may be avoided in these cases. Methods: Ninety-six consecutive patients with invasive breast cancer and tumour size less than 2 centimeters by mammography, had lymphoscintigraphy with colloidal 99Tc and radioisotope-guided sentinel lymph node biopsy in the University Hospital of Zaragoza from 1999 to 2005.Pathological assessment included serial sections of the sentinel lymph node with immunohistochemistry for cytokeratins in selected cases. Results: Sentinel lymph node biopsy was negative in 57 patients. There were 56 females and 1 male. Median age was 57 years (range 24–87). Median pathological tumor size was 15 mm (range 5–31). Location of the sentinel lymph node was axillary in 47patients, internal mammary in 0 patients, and both in 10 patients. Median number of resected lymph nodes was 2 (range 1–4). With median follow-up of 33 months, no local or systemic relapses have occurred. Conclusions: Avoidance of regional lymph node dissection is safe in patients with breast cancer and histologically negative sentinel lymph node biopsy. No significant financial relationships to disclose.
The phenomenology of near-death experiences
Authors: B Greyson, I Stevenson
Journal: American Journal of Psychiatry (1980)

The authors studied retrospectively 78 reports of "near-death experiences using subjects narratives and questionnaires, interviews, and medical records. Prior experiences suggestive of transcendence of death were more common among these subjects than among control populations, but prior experiences suggestive of extrasensory phenomena were less common. Subsequent changes in attitudes were more common than among subjects in other studies who had had psychic experiences. The influence of cultural and psychological factors, sensory deprivation, and reflex adaptive responses to stress explain some but not all of the features of near-death experiences. Their potential value to our conceptualization of dying and to suicide prevention and the care of the terminally ill justifies further investigation.