tbuckley/cabot-search huggingface dataset:
Tissue inhibitor of metalloproteinases 1 (TIMP-1) and tumor type M2 pyruvate kinase (TuM2-PK) were compared with established markers in advanced colorectal cancer
Authors: S. Siepmann, D. Pollmann, R. Geppert, K. D. Wernecke, K. Possinger, D. Lueftner
Journal: Journal of Clinical Oncology (2006)

13537 Background: Recently, a high expression of TIMP-1 was demonstrated by immunohistochemistry in colorectal cancer (CRC). TIMP-1 can also be detected in plasma of those patients (pts). We investigated the longitudinal concentrations of TIMP-1 in 37 pts with advanced CRC and correlated the monitoring performance of TIMP-1 to CEA and CA 19–9 as established markers of tumor load in CRC. In addition, the plasma level of TuM2-PK as novel marker of disease activity was integrated into the analysis. Methods: Plasma TIMP-1 (Bayer Diagnostics/Oncogene Science, Tarrytown/Boston, USA) and TuM2-PK (Schebo Biotech, Giessen, Germany) levels were measured using standardized ELISA assays while serum CEA and CA 19–9 were determined using chemiluminescence immunoassays (Bayer Diagnostics, Tarrytown/NY). The nonparametric analysis of variance for repeated measurements by Brunner was used to test for time effects between the selected 3 time points: 1. baseline at initiation of systemic chemotherapy for metastatic disease; 2: best response; 3: later progression. Results: We grouped 37 pts with regard to best response to chemotherapy as follows: complete or partial remission (CR/PR): n=10; stable disease (SD): n=21; primary progressive disease (PD): n=6. TIMP-1 and TuM2-PK concentrations increased significantly from baseline to progression (p&lt;0.001 and p=0.003, respectively). The plasma levels of patients with objective response (CR/PR) dropped significantly for TuM2-PK (p=0.001) and TIMP-1 (p=0.001), while CA 19–9 and CEA did not change (p=0.94 and p=0.10, respectively). No significant change could be demonstrated in the SD group for TuM2-PK (p=0.26), TIMP-1 (p=0.69) and for CEA (p=0.25), whereas CA 19–9 concentrations decreased significantly (p=0.04). Conclusions: Innovative markers like TIMP-1 and TuM2-PK provided a much higher monitoring quality than established markers like CEA and CA 19–9 in advanced CRC. As the later cancer-associated proteins are recommended by internationally acknowledged guidelines, larger comparative trials are warranted asking the important question whether a replacement of CEA by one or a panel of new markers may provide additional clinical information. No significant financial relationships to disclose.
Abstract 14333: YJP14, the Standardized Extract of Lindera Obtusiloba, Ameliorate Endothelial Dysfunction and Suppress Atherosclerotic Plaque Progression by Suppressing NADPH Oxidase-Induced Reactive Oxygen Species Generation in Murine Atherosclerosis Model
Authors: Sang-Hyun Ihm, Ok-Ran Kim, Jung-Ok Lee, Dong Hyun Park, Valerie B. Schini-Kerth, Kyoung Rak Kim, Min-Ho Oak, Kiyuk Chang
Journal: Circulation (2012)

Background:  YJP14, the standardized extract of  Lindera obtusiloba  which is traditionally used for cardiovascular diseases in Korea, is recently entered into IND investigation for prevention of endothelial dysfunction. The aim of this study was to determine whether YJP14 prevents the development of atherosclerosis including endothelial dysfunction and formation of atherosclerotic plaque in ApoE -/-  mice model.    Methods:  The effect of YJP14 on different parameters was compared to losartan (LSRT) that was reported to improve endothelial dysfunction. Three groups of 14 male ApoE -/-  mice (Western Diet) and one group of 14 male C57BL/6 (negative control, normal chow) were studied. YJP14 (100mg/Kg/day), LSRT (30mg/Kg/day) and vehicle (Veh, 0.5 % CMC) was administrated by gavage for 20 weeks, from 8 to 28 weeks.    Results:  YJP14 slightly, but significantly, decreased the level of LDL, not HDL and TG in ApoE -/-  mice. In addition, YJP14 and LSRT prevented endothelial dysfunction (Figure 1), which were, at least in part, associated with reduced vascular expression of NADPH oxidase subunit (p47, p22) and formation of ROS assessed by IHC and DHE staining. Related to vascular remodeling, atherosclerotic plaque lesion area was reduced by YJP14 (0.32 vs. 0.53 mm 2  of  control group, p   Conclusion:  Taken together, the present findings indicate that YJP14 effectively prevent atherosclerosis plaque progression and is a promising candidate as vasopretective agent.
Bevacizumab (Bv) in the adjuvant treatment of HER2-negative breast cancer: Final results from Eastern Cooperative Oncology Group E5103.
Authors: Kathy Miller, Anne M. O'Neill, Chau T. Dang, Donald W. Northfelt, William John Gradishar, Lori J. Goldstein, Ingrid A. Mayer, Adam Brufsky, Stuart Hunegs Bloom, Joseph A. Sparano, Amye Tevaarwerk, Kevin R. Fox, Carolyn Bennett Hendricks, Ernie P. Balcueva, George W. Sledge
Journal: Journal of Clinical Oncology (2014)

500 Background: Bv improves progression-free survival (PFS) but not overall survival (OS) in MBC. E5103 added Bv to adjuvant therapy in patients (pts) with HER2- disease. Methods: Pts were assigned 1:2:2 to one of three treatment arms. In addition to doxorubicin and cyclophosphamide followed by wkly paclitaxel, pts received either placebo (Arm A – AC>T), Bv during chemo (Arm B - BvAC>BvT), or Bv during chemo -> Bv monotherapy for 10 cycles (Arm C – BvAC>BvT>Bv). Randomization was stratified and Bv dose adjusted for choice of AC schedule. Radiation and hormonal therapy were administered concurrently with Bv in Arm C. The primary endpoint was invasive disease free survival (IDFS) requiring 426 IDFS events across Arms C and A to detect hazard ratio (HR) of 0.75 with 80% power using a one-sided 2.5% (two-sided 5%) stratified log rank test. Results: 4,994 pts were enrolled. Median age 52; 64% ER+, 27% LN-; 80% received ddAC. Chemotherapy associated adverse events (AEs) including myelosuppression (Grade 4 neutropenia 17/20/21%) and neuropathy (Grade > 3 - 8/8/9%) were similar across all arms. Grade > 3 hypertension/thrombosis/proteinuria/hemorrhage was reported by 8/3/<1/<1% of Bv-treated pts. The cumulative incidence of clinical CHF at 15 mos. was 1.0/1.9/3.0%. Emergent unblinding was uncommon and similar among all arms (3/4/4% respectively) but Bv exposure was less than anticipated with ~24% of pts in Arm B and ~55% of pts in Arm C discontinuing Bv before completing planned therapy. With a median follow-up of 47.5 mos. and 430 IDFS events across Arms C and A, 5-yr IDFS (95%CI) was 77%(70.9%-81.2%/76%(71.5%-79.8%)/80%(77%-82.5%) respectively. Conclusions: Incorporation of Bv into anthracycline and taxane containing adjuvant therapy does not improve IDFS or OS in pts with high risk HER2- breast cancer. Bv did increase AEs but no unexpected AEs were encountered. Longer duration therapy is unlikely to be feasible given the high rate of early discontinuation due to all causes. Clinical trial information: NCT00433511. C vs A HR (0.95 CI) Two-sided P-value IDFS overall 0.87 (0.70-1.08) 0.17 ER/PgR + 0.93 (0.77-1.22) 0.61 ER/PgR - 0.77 (0.57-1.03) 0.08 OS Overall 0.89 (0.68-1.17) 0.41 ER/PgR + 1.01 (0.67-1.53) 0.97 ER/PgR - 0.77 (0.53-1.12) 0.17
Extra £3.8bn for NHS will be undermined by public health and social care cuts, experts predict
Authors: Gareth Iacobucci
Journal: BMJ (2015)

The government has committed itself to investing £3.8bn (€5.4bn; $5.8bn) above inflation in the NHS in England next year in response to the growing financial pressure on the healthcare system.

The announcement, made ahead of the Treasury’s spending review from the chancellor of the exchequer, George Osborne, will be seen as a victory for NHS England’s chief executive, Simon Stevens, who argued for the government to “frontload” the promised £8bn a year in extra funding for the NHS by 2020 to provide “a workable funding settlement” for the next two years.

Commenting after the deal was announced, Stevens said, “In the context of constraints on overall public spending, our case for the NHS has …
Abstract 14502: Soluble Vascular Endothelial Growth Factor Receptor-2 as a Predictor of the New Onset of Diabetes Following Smoking Cessation
Authors: Hiromichi Wada, Suichi Ura, Noriko Satoh-Asahara, Masaharu Akao, Mitsuru Abe, Tatsuya Morimoto, Koh Ono, Akira Shimatsu, Yuko Takahashi, Koji Hasegawa
Journal: Circulation (2013)

Background: Although smoking cessation (SC) rapidly decreases the risk of cardiovascular events, it is also associated with the development of diabetes. However, biomarkers which predict the new on...
Alternate Metabolic Programs Define Regional Variation of Relevant Biological Features in Renal Cell Carcinoma Progression
Authors: Samira A. Brooks, Amir H. Khandani, Julia R. Fielding, Weili Lin, Tiffany Sills, Yueh Lee, Alexandra Arreola, Mathew I. Milowsky, Eric M. Wallen, Michael E. Woods, Angie B. Smith, Mathew E. Nielsen, Joel S. Parker, David S. Lalush, W. Kimryn Rathmell
Journal: Clinical Cancer Research (2016)

Clear cell renal cell carcinoma (ccRCC) has recently been redefined as a highly heterogeneous disease. In addition to genetic heterogeneity, the tumor displays risk variability for developing metastatic disease, therefore underscoring the urgent need for tissue-based prognostic strategies applicable to the clinical setting. We have recently employed the novel PET/magnetic resonance (MR) image modality to enrich our understanding of how tumor heterogeneity can relate to gene expression and tumor biology to assist in defining individualized treatment plans.ccRCC patients underwent PET/MR imaging, and these images subsequently used to identify areas of varied intensity for sampling. Samples from 8 patients were subjected to histologic, immunohistochemical, and microarray analysis.Tumor subsamples displayed a range of heterogeneity for common features of hypoxia-inducible factor expression and microvessel density, as well as for features closely linked to metabolic processes, such as GLUT1 and FBP1. In addition, gene signatures linked with disease risk (ccA and ccB) also demonstrated variable heterogeneity, with most tumors displaying a dominant panel of features across the sampled regions. Intriguingly, the ccA- and ccB-classified samples corresponded with metabolic features and functional imaging levels. These correlations further linked a variety of metabolic pathways (i.e., the pentose phosphate and mTOR pathways) with the more aggressive, and glucose avid ccB subtype.Higher tumor dependency on exogenous glucose accompanies the development of features associated with the poor risk ccB subgroup. Linking these panels of features may provide the opportunity to create functional maps to enable enhanced visualization of the heterogeneous biologic processes of an individual's disease. Clin Cancer Res; 22(12); 2950-9. ©2016 AACR.
Toward Minimizing Overtreatment and Undertreatment of Ductal Carcinoma In Situ in the United States
Authors: Grace L. Smith
Journal: Journal of Clinical Oncology (2016)

Radiation therapy (RT) is an effective adjuvant local therapy for ductal carcinoma in situ (DCIS) of the breast. RT decreased ipsilateral breast events by approximately half after breastconserving surgery (BCS), from 18% to 8% at 5 years and from 28% to 13% at 10 years in a meta-analysis of randomized prospective studies that enrolled patients with diverse pathologic features. However, this local benefit never translated into a survival benefit in these meta-analytic data. This is in contrast to adjuvant RT after BCS for early-stage invasive breast cancer, where prospective studies clearly demonstrated up to a 7.8% improvement in risk of breast cancer death at 15 years, particularly in patients at higher baseline risk of local recurrence. Thus, to date, for any individual patient with DCIS, the risk-benefit discussion for or against adjuvant RT has generally hinged upon the patient’s expected absolute local benefit from RT. Fundamentally, the absolute local benefit from RT depends on the patient’s baseline risk features. For example, in a patient with high-risk pathologic features such as high histologic or nuclear grade, the risk of in-breast recurrence is estimated to be 24% at 5 years with BCS alone, compared with a risk of 12% at 5 years with BCS plus RT. In such a patient, with such a high absolute recurrence risk and a large absolute benefit with RT, adjuvant treatment is typically recommended. In contrast, in a patient with lower risk features, in-breast recurrence is only 3% at 5 years with BCS alone. A local benefit of adjuvant RT is still seen in such patients, with an in-breast recurrence rate of only 0.4% at 5 years after RT. However, with low absolute recurrence risk after BCS alone and small absolute benefit after adding RT, BCS alone is frequently considered an acceptable treatment recommendation.
Phase (Ph) I evaluation of the dolastatin analogue synthadotin (SYN-D; ILX651): Pooled data analysis of three alternate schedules in patients (pts) with advanced solid tumors
Authors: L. A. Hammond, F. Ruvuna, C. C. Cunningham, S. Ebbinghaus, E. Rubin, A. Mita, E. Hersh, J. P. Eder, J. Weiss, E. K. Rowinsky
Journal: Journal of Clinical Oncology (2004)

3068
Lithium's effect of parathyroid hormone
Authors: B M Davis, A Pfefferbaum, S Krutzik, K L Davis
Journal: American Journal of Psychiatry (1981)

Lithium has been reported to raise serum calcium and lower serum phosphate concentrations and to increase urinary calcium excretion. Because these changes may be effects of parathyroid hormone (PTH), PTH was measured in 19 patients receiving lithium. PTH was significantly higher in these patients than in 150 normal subjects. For all patients serum calcium concentrations correlated significantly with serum lithium concentrations. These results indicate that lithium may cause biochemical hyperparathyroidism. Secondary hyperparathyroidism in certain patients with lithium nephrotoxicity is also possible.
METRIC phase III study: Efficacy of trametinib (T), a potent and selective MEK inhibitor (MEKi), in progression-free survival (PFS) and overall survival (OS) compared with chemotherapy (C) in patients (pts) with BRAF<sub>V600/k </sub>mutant advanced or metastatic melanoma (MM).
Authors: Caroline Robert, Keith T. Flaherty, Peter Hersey, Paul D. Nathan, Claus Garbe, Mohammed M. Milhem, Lev V. Demidov, Jessica C. Hassel, Piotr Rutkowski, Peter Mohr, Reinhard Dummer, Uwe Trefzer, James M. G. Larkin, Jochen Utikal, Michelle Casey, Laurie Jill Sherman, Wendy A. Crist, Frank S. Wu, Kiran Patel, Dirk Schadendorf
Journal: Journal of Clinical Oncology (2012)

LBA8509 The full, final text of this abstract will be available at abstract.asco.org at 12:01 AM (EDT) on Monday, June 4, 2012, and in the Annual Meeting Proceedings online supplement to the June 20, 2012, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Monday edition of ASCO Daily News.
Phase I trial of anti-CD3-stimulated CD4+ T cells, infusional interleukin-2, and cyclophosphamide in patients with advanced cancer.
Authors: B D Curti, A C Ochoa, G C Powers, W C Kopp, W G Alvord, J E Janik, B L Gause, B Dunn, M S Kopreski, R Fenton, A Zea, C Dansky-Ullmann, S Strobl, L Harvey, E Nelson, M Sznol, D L Longo
Journal: Journal of Clinical Oncology (1998)

PURPOSE We performed a phase I trial to determine whether in vivo expansion of activated CD4+ T cells was possible in cancer patients. 111Indium labeling was used to observe trafficking patterns of the infused stimulated CD4+ T cells. The influence of cyclophosphamide (CTX) dosing on immunologic outcome was also examined. PATIENTS AND METHODS Patients with advanced solid tumors or non-Hodgkin's lymphoma received CTX at 300 or 1,000 mg/m2 intravenously (i.v.). Leukapheresis was performed to harvest peripheral-blood mononuclear cells (PBMCs) either just before the CTX dose, or when the patient was either entering or recovering from the leukocyte nadir induced by CTX. An enriched population of CD4+ T cells was obtained by negative selection. The CD4+ T cells were activated ex vivo with anti-CD3, cultured with interleukin-2 (IL-2) for 4 days, and adoptively transferred. After adoptive transfer, patients received IL-2 (9.0 x 10(6) IU/m2/d) by continuous infusion for 7 days. RESULTS The absolute number of CD4+, CD4+/DR+, and CD4+/CD45RO+ T cells increased in a statistically significant fashion in all cohorts after the first course of therapy. The degree of CD4 expansion was much greater than CD8 expansion, which resulted in a CD4:CD8 ratio that increased in 26 of 31 patients. The greatest in vivo CD4 expansion occurred when cells were harvested as patients entered the CTX-induced nadir. One complete response (CR), two partial responses (PRs), and eight minor responses were observed. Trafficking of 111Indium-labeled CD4 cells to subcutaneous melanoma deposits was also documented. CONCLUSION CD4+ T cells can be expanded in vivo in cancer patients, which results in increased CD4:CD8 ratios. The timing of pheresis in relation to CTX administration influences the degree of CD4 expansion. Tumor responses with this regimen were observed in a variety of tumors, including melanoma and non-Hodgkin's lymphoma; a high percentage of patients had at least some tumor regression from the regimen that produced the greatest CD4+ T-cell expansion.
A phase-II study evaluatin safety and efficacy with weekly paclitaxel and carboplatin as a primary treatment for patients with advanced epithelial ovarian cancer (EOC)
Authors: T. Safra, R. Bernstein Molho, D. Grisaru, S. Spigel, R. Geva, D. Matcejevsky, M. Inbar, J. Menzcer, T. Levy
Journal: Journal of Clinical Oncology (2006)

5077 Background: The standard chemotherapy for epithelial ovarian cancer (EOC) is carboplatin and paclitaxel every 3 weeks together with debulking surgery. This phase II trial was designed to determine the safety and efficacy of weekly carboplatin and paclitaxel treatment in patients with EOC. Methods: Between October 2003 to August 2005, 37 patients with stage Ic-IV epithelial ovarian, tubal or primary peritoneal carcinoma were enrolled into the study. Carboplatin at AUC=2 and paclitaxel at 80 mg/m 2 were administered on days 1,8,15 of a 28-day cycle. Cytoreductive surgery was performed as primary treatment or after 3 cycles of neoadjuvant chemotherapy with additional chemotherapy after the surgery. Results: Median age of the patients was 67 (range 49–82). A mean of 6 chemotherapy cycles were administered (range 3–8). Median time of follow-up (from the beginning of chemotherapy until the last follow-up visit) was 15.57 months (range 0.2–26months). Thirty-three patients were evaluable for response. Complete response (CR) was observed in 26 patients (78.8%) and partial response (PR) in 7 (21.8%). By the time of data collection 13 out of 33 women (39.4%) experienced recurrent or persistent disease and one patient (3%) died from progressive disease during 2 nd line chemotherapy. Since 20 out of 33 patients are still free of disease and all but one are still alive, it is too early to evaluate time to progression (TTP) and overall survival (OS). The median time to disease recurrence or progression after completion of primary chemotherapy was 7.5+ months (0.2–18.2+). As for toxicity; grade 3 and 4 neutropenia were seen in 5 (13.5%) and one patient (2.7%) respectively. There was no neutropenic fever. Other grade 3 and 4 hematologic toxicities were not observed. Six (16.2%) and 5 (13.5%) patients needed G-CSF and Epoetin support respectively. The main non-hematologic toxicities were alopecia (grade 1) and fatigue (grade 3 in two patients). Only two patients (5.4%) experienced grade 3 neuropathy. Conclusion: Weekly treatment with carboplatin and paclitaxel is feasible and well tolerated. The low toxicity rate especially regarding neuropathy warrants further investigation of this regimen. No significant financial relationships to disclose.
Docetaxel-estramustine in localized high-risk prostate cancer: Results of the French Genitourinary Tumor Group GETUG 12 phase III trial.
Authors: Karim Fizazi, Agnes Laplanche, Francois Lesaunier, Remy Delva, Gwenaelle Gravis, Frederic Rolland, Frank Priou, Jean Marc Ferrero, Nadine Houede, Loic Mourey, Christine Theodore, Ivan Krakowski, Jean François Berdah, Marjorie Baciuchka, Brigitte Laguerre, Jean-Louis Davin, Anne-Laure Martin, Muriel Habibian, Laura Faivre, Stephane Culine
Journal: Journal of Clinical Oncology (2014)

5005 Background: Docetaxel-estramustine improves survival in patients (pts) with castrate-resistant prostate cancer (CaP). This phase III trial assessed docetaxel-estramustine in pts with high-risk localized CaP. Methods: Eligibility included non-pretreated high-risk localized CaP, defined as ≥1 of the following criteria: T3-T4, Gleason score (GS)≥8, PSA≥ 20 ng/mL, pN+ (stratification factors). All pts had a staging pelvic lymph node dissection. Pts were randomly assigned to either goserelin 10.8 mg every 3 months for 3 years and 4 cycles of docetaxel 70 mg/m2 q3w + estramustine 10 mg/kg/d d1-5 (ADT+DE arm) or goserelin alone (ADT arm). Local therapy was administered at 3 months. The primary endpoint is progression-free survival (PFS); events=PSA relapse, radiographic relapse, death. The planned number of pts was 400, to detect a 12% difference at 4 years with a power of 80% and a type I error of 0.05 (two-sided Logrank test). Preliminary results indicated a better PSA response rate (PSA ≤ 0.2 ng/mL: 34% in the ADT+DE arm vs 15% in the ADT arm [p< 0.0001]), neutropenic fever in 2%, and no negative impact on QoL at 1 year in the ADT+DE arm (Fizazi, Eur J Cancer 2012; 48:209-17). Here we report PFS results. Results: 413 pts were accrued. With a median follow-up of 7.6 years, PFS was marginally improved in the ADT+DE arm: 8-year PFS rate: 62% [55–69] in the ADT+DE arm vs 53% [45–60] in the ADT arm (adjusted HR: 0.75 [0.55-1.01], p=0.06). In pts with a GS<8, the 8-year PFS rate was 69% [60-78] (ADT+DE) and 51% [41-61] (ADT) (HR: 0.55 [0.36-0.84], interaction test =0.06 for GS). A non-significant trend favoring ADT+DE was found for clinical PFS (HR: 0.79 [0.55-1.13]). No long-term toxicity signal was detected, with no toxic death. The 8-year cumulative incidence of second cancers (11% vs 10%) was similar in the two arms. The 8-year OS rate is 83% [77–89] with no difference between treatment arms (HR: 0.94 [0.60-1.49]). In pts with a GS<8, the 8-year OS rate was 94% [89-98] (ADT+DE) and 85% [78-92] (ADT) (HR: 0.40 [0.17-0.91], interaction test: p=0.02). Conclusions: Docetaxel-estramustine is associated with a borderline significant reduction in the risk of relapse or death in high-risk prostate cancer. Clinical trial information: NCT00055731.
Superior Efficacy of VTD over VCD As Induction Therapy for Autotransplantation-Eligible, Newly Diagnosed, Myeloma Patients
Authors: Michele Cavo, Lucia Pantani, Annalisa Pezzi, Federica Cavallo, Maria Teresa Petrucci, Francesco Di Raimondo, Francesca Patriarca, Anders Waage, Elena Zamagni, Vittorio Montefusco, Monica Galli, Barbara Gamberi, Giuseppe Rossi, Paola Tacchetti, Mariella Grasso, Sonja Zweegman, Massimo Offidani, Stelvio Ballanti, Renato Zambello, Anna Marina Liberati, Renato Bassan, Patrizia Pregno, Antonio Palumbo, Pieter Sonneveld
Journal: Blood (2014)
Rooting Out Gun Violence
Authors: Debra Malina, Stephen Morrissey, Edward W. Campion, Mary Beth Hamel, Jeffrey M. Drazen
Journal: New England Journal of Medicine (2015)

Here we are again. Less than a year ago, an editorial in the Journal by Kassirer reexamined the massive public health problem of gun violence in the United States,1 and a Perspective article by Sacks, born of a personal tragedy, lamented the defunding of research on firearm-injury prevention.2 Kassirer called for electing “lawmakers at all levels of government with the courage to defy gun lobbyists,” so that essential regulatory changes can finally be enacted — as physicians, public health experts, and others have been recommending for decades. But in early December, the day after a young couple turned up at . . .