tbuckley/cabot-search huggingface dataset:
A retrospective analysis of patients with renal cancer receiving temsirolimus within a named patient program.
Authors: J. S. Pascoe, S. Whitmarsh, S. I. Collins, N. D. James, E. Porfiri
Journal: Journal of Clinical Oncology (2010)

e15140 Background: Temsirolimus has been shown to improve outcomes in patients with metastatic renal cell carcinoma and poor prognostic factors. We present the outcomes of 36 patients treated within a named patient program in our center. Methods: All patients who received temsirolimus were included. Information was obtained through retrospective review of notes and pharmacy records. Baseline characteristics, prognostic features (performance status, time from diagnosis, no of sites of metastatic disease, hemoglobin, and corrected calcium) and previous treatments were recorded for all patients. Outcome measures recorded were response rate, progression free survival (PFS), overall survival (OS), and toxicities. Results: In 36 patients median age was 63 (range 43-81), M/F: 24/12, ECOG PS 0/1/2/3: 8/15/11/2. Number of poor prognostic features at baseline were 0/1/2/3/4/5 in 3/10/9/10/3/1 patients respectively. Number of previous systemic treatments was 0/1/2/3 in 12/13/10/1 patients. 32 patients had undergone a prior nephrectomy. Previous treatments included interferon alpha (20), sunitinib (11), sorafenib (3). Response was assessed in 28 patients as follows PR (3), SD (11), and PD (14). 8 patients did not undergo response assessment as they received less than 8 weeks treatment due to death (5), toxicity (2), and patient choice (1). Median OS was 7.59 months (95% CI 4.96 – upper limit undefined), median PFS was 3.22 months (95% CI 2.42 to 5.82). A nonsignificant difference in OS and PFS was observed between pretreated patients (OS 6.41 months, PS 2.66 months) and untreated patients (OS not reached at 18 months and PFS 8.72 months). Grade 3-4 toxicities included mucositis (4), pnemonitis (3), elevated creatinine (4), and hyperglycaemia (5). Conclusions: In this patient group PFS and OS were inferior to that described by Hudes et al however 67% of our patients were pretreated. In untreated patients OS and PFS appeared improved although not all patients were poor prognosis. All patients n = 36 Pretreated n = 24 Untreated n = 12 OS months (95% CI) 7.59 (4.96-NA) 6.41 (3.84-10.1) Not reached at 18 months (4.21-NA) PFS months(95% CI) 3.22 (2.46-5.82) 2.66 (1.97- 5.42) 8.72 (2.43-NA) PD 27 (75%) 20 (83%) 7 (58%) Abbreviation: NA, undefined. No significant financial relationships to disclose.
Dietary berries and ellagic acid diminish estrogen-mediated mammary cancer in the ACI rat model
Authors: Harini S. Aiyer, Cidambi Srinivasan, Ramesh C. Gupta
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

2267 

Elevated levels of estrogen are associated with higher risk for breast cancer. The induction of mammary tumors in ACI rats by estrogen mimics the human scenario more closely than tumors induced by environmental carcinogens. This renders the model more useful for chemopreventive interventions with translational value. Historically, dietary chemoprevention studies have used relatively high doses in order to achieve efficacy which makes applying bench-side research to bed-side improbable. Any potent chemopreventive agent must be tested at realistically achievable doses in a suitable animal model for integrating into clinical practice. In this study, we have tested feasible doses of dietary berries and ellagic acid to reduce estrogen-mediated mammary tumorigenesis. Female ACI rats (7-8 wks) were fed either AIN-93M diet (n=25) or diet supplemented with either dehydrated blueberries (n=18) and black raspberries (n=18) at 2.5% w/w or ellagic acid (n=18) at 400 ppm. Two weeks later, animals received implants of silastic tubes containing 27 mg 17β- estradiol. Animals were monitored for tumor appearance by palpation throughout the course of the study. Animals were euthanized 25 weeks after estrogen treatment and number of tumors and tumor volumes were determined. Tumors in animals fed control diet first appeared after 90 d of estrogen implantation. Tumor appearance was, however, moderately, but insignificantly, delayed by 18, 21 and 22 d in animals fed diets supplemented with blueberries, black raspberries and ellagic acid, respectively. At the termination of the experiment, no difference was observed in the tumor incidence between the control diet and experimental diets, however, other tumor indices were reduced by intervention. Compared with control group (average tumor volume = 685± 200 mm3 and tumor multiplicity = 8.0± 2.4), ellagic acid reduced the tumor burden by 75% (p<0.005) and tumor multiplicity by 44% (p70% (p<0.005) and tumor multiplicity by 37% (p=0.07). Blueberries showed a moderate (42%) reduction in tumor volume but tumor multiplicity was essentially unaffected. These data demonstrate chemoprotective effects of both berries and ellagic acid against the carcinogenic activity of the estrogen. Based on known ellagic acid contents - high in black raspberries (1,500 ppm) and low in blueberries (<100 ppm), our data suggests that, in addition to ellagic acid, there may be other constituent(s) in these berries that are responsible for the observed chemoprotective effects.
Pembrolizumab (MK-3475) versus paclitaxel as second-line therapy for advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma: Phase 3 KEYNOTE-061 study.
Authors: Atsushi Ohtsu, Josep Tabernero, Yung-Jue Bang, Charles S. Fuchs, Linda Sun, Zhen Wang, Ildiko Csiki, Minori Koshiji, Eric Van Cutsem
Journal: Journal of Clinical Oncology (2016)

TPS183 Background: Pembrolizumab (pembro) is a humanized monoclonal antibody against PD-1 that prevents PD-1 from interacting with PD-L1 and PD-L2 and permits activation of an antitumor immune response. In KEYNOTE-012, pembro showed a manageable safety profile and a 22% ORR in pts with advanced gastric cancer. The randomized, open-label, phase 3 KEYNOTE-061 study (NCT02370498) is designed to compare the efficacy and safety of pembro with those of standard-of-care paclitaxel in the second-line treatment of advanced gastric cancer. Methods: KEYNOTE-061 is designed for patients with metastatic or unresectable gastric or GEJ adenocarcinoma that progressed after first-line treatment with platinum and fluoropyrimidine doublet chemotherapy. Patients with HER2/neu-positive tumors are eligible if they have documented progression on a regimen that also included trastuzumab. Other key eligibility criteria include measurable disease per RECIST v1.1, ECOG PS 0-1, no chemotherapy within 2 wk of first dose of study drug, and provision of a newly obtained or archival tumor sample for assessing PD-L1 status. Eligible pts are randomized 1:1 to receive pembro 200 mg Q3W or paclitaxel 80 mg/m 2 IV on days 1, 8, and 15 of each 28-d cycle. Treatment will continue until disease progression, intolerable toxicity, refusal by pt or investigator, or completion of 24 mo of therapy (pembro arm only). Pts in the pembro arm who have a CR after ≥ 24 wk may discontinue after ≥ 2 doses following initial CR. Clinically stable pts who progress per RECIST v1.1 may continue pembro at the discretion of the investigator until a confirmatory CT scan performed ≥ 4 wk later. Response will be assessed every 6 wk for the first 6 mo and every 12 wk thereafter per RECIST v1.1 by central review and per RECIST adapted for immunotherapy response patterns. AEs will be assessed throughout treatment and for 30 d thereafter (up to 90 d for serious AEs). Primary efficacy end points are PFS per RECIST v1.1 and OS in pts with PD-L1 + tumors. Secondary end points include PFS and OS in all pts, time to progression, ORR, and duration of response. Enrollment in KEYNOTE-061 is ongoing and will continue until up to 720 pts are enrolled. Clinical trial information: NCT02370498.
Pan-Raf co-operates with PI3K-dependent signalling and critically contributes to myeloma cell survival independently of mutated RAS
Authors: E Müller, S Bauer, T Stühmer, A Mottok, C-J Scholz, T Steinbrunn, D Brünnert, A Brandl, H Schraud, S Kreßmann, A Beilhack, A Rosenwald, R C Bargou, M Chatterjee
Journal: Leukemia (2016)
High prevalence of hepatitis G virus (HGV) infection as compared to HCV in patients undergoing hemodialysis in an university centre in Belgium
Authors: L Sheng, A Widyastuti, H Kosala, J Donck, Yves Vanrenterghem, E Setioso, A Soumillion, C Verslype, R Schelstraete, MP Emonds, G Hess, SH Yap
Journal: Hepatology (1997)
Cisplatin versus cetuximab plus concomitant radiotherapy in locally advanced head and neck cancer: A meta-analysis of published trials.
Authors: Sandro Barni, Andrea Coinu, Karen Borgonovo, Mary Cabiddu, Marco Cremonesi, Fausto Petrelli
Journal: Journal of Clinical Oncology (2014)

6014 Background: Concurrent chemoradiotherapy (CTRT) or RT + cetuximab (RT + CET) are both treatment options for the treatment of locally advanced head and neck cancer (HNC). The efficacy of these two treatment modalities for patients with locoregionally advanced or inoperable HNC however has never been compared. Methods: We conducted a systematic review and meta-analysis by searching in PubMED, EMBASE, SCOPUS, Web of Science and The Cochrane Register of Controlled Trials, to compare CTRT and RT + CET in locally advanced HNC. Risk ratios (RRs) with 95% confidence intervals (95%CIs) were calculated for pre-specified endpoints as 2-year overall survival (OS), 2-year disease free-survival (DFS), 2-year loco-regional relapse (LRR) and 2-year distant metastases (DM). Meta-analysis was performed using the fixed- or random-effects models. Results: 15 trials for a total of 1,808 patients, were included. Concurrent CTRT significantly improved 2-year OS (RR=0.66, 95% CI 0.46-0.94; P=0.02), 2-year DFS (RR=0.68, 95% CI 0.53-0.87; P=0.002) and 2-year LRR (RR=0.63, 95% CI 0.45-0.87; P=0.005) compared to RT + CET. The absolute risk differences were 12%, 17% and 10%. Risk of distant metastases was identical (RR=1.01, 95%CI 0.69-1.48; P=0.94). Conclusions: Platinum-based CTRT is associated with a better 2-year OS and locoregional control compared to RT + CET, and still remains the standard of care in locally advanced HNC until prospective trials can demonstrate equivalence. Endpoint CTRT RT + CET Risk ratio (95% CI) 2-yr OS 71 % 60.7 % 0.66 (0.46-0.94) P=0.02 2-yr DFS 61.7 % 43.1 % 0.68 (0.53-0.87) P=0.002 2-yr LRR 19.6% 32.3% 0.63 (0.45-0.87) P=0.005
Oncogenic Transcriptional Programs Controlled by TLX1/HOX11 and TLX3/HOX11L2 in T-ALL.
Authors: Giusy Della Gatta, Teresa Palomero, Maria Luisa Sulis, Xavier Solé, Wei Keat Lim, Kim De Keersmaecker, Pedro Jose Real Luna, Valeria Tosello, Fotini Gounari, Barbara Kee, Jack Lenz, Michelle Kelliher, Peter D. Aplan, Jules P.P. Meijerink, Andrea Califano, Adolfo Ferrando
Journal: Blood (2009)
Endothelial progenitor cells from human fetal aorta cure diabetic foot in a rat model
Authors: Wan-Ni Zhao, Shi-Qing Xu, Jian-Feng Liang, Liang Peng, Hong-Lin Liu, Zai Wang, Qing Fang, Meng Wang, Wei-Qin Yin, Wen-Jian Zhang, Jin-Ning Lou
Journal: Metabolism (2016)
Prognostic value and analytical performance (reproducibility) of Ki67 index in anaplastic oligodendroglial tumors: A translational study of the EORTC Brain Tumor Group.
Authors: M. Preusser, R. Hoeftberger, A. Woehrer, M. Kouwenhoven, M. Kros, A. Idbaih, A. A. Brandes, H. Heinzl, T. Gorlia, M. J. Van Den Bent
Journal: Journal of Clinical Oncology (2010)

2029 Background: The prognostic value and clinical utility of Ki67 tumor cell proliferation index in anaplastic oligodendroglial tumors is unclear. Methods: We performed anti-Ki67 immunostaining (Mib-1 antibody) of formalin-fixed and paraffin embedded tumor specimens of 70 patients that were treated in the Phase III EORTC trial 26951 investigating adjuvant chemotherapy with procarbazine, lomustine and vincristine (PVC) in newly diagnosed anaplastic oligodendroglial tumors (J Clin Oncol 2006). Ki67 index was independently assessed by 3 observers, 1 of whom performed re-assessment several weeks after initial evaluation. Lin's concordance correlation coefficient (CCC), Bland-Altman plots and Cohen′s kappa (k) were used to evaluate pair-wise observer agreement on Ki67 index values. The average Ki67 index was correlated to clinical (patient age, performance status, type of surgery and adjuvant therapy, tumor location), centrally assessed histopathological (diagnosis, presence of high cellularity, nuclear and endothelial abnormalities, mitoses, necrosis) and molecular features (1p19q loss, EGFR amplification, trisomy 7, loss of chromosome 10 or 10q). The association of Ki67 index, clinical, histopathological and molecular features with progression-free survival (PFS) and overall survival (OS) were assessed using log-rank test, cox model, and bootstrap validation. Results: Ki67 indices ranged from 0.3 to 73% (median 19%) and there was high inter- and intraobserver agreement (CCC > 0.9, k > 0.7). High Ki67 index (cut-off 19%) was significantly associated with presence of high cellularity, endothelial abnormalities, mitoses and necrosis. At multivariate analysis, low Ki67 index (cut-off 19%; p = 0.001), 1p19q loss (p = 0.01) and absence of EGFR amplification (p = 0.03) correlated significantly with favorable PFS. Low Ki67 index (p < 0.01) and 1p19q loss (p = 0.02) were independently and significantly associated with favorable OS. Conclusions: Ki67 index is a strong and reproducibly assessable prognostic factor in anaplastic oligodendroglial tumors. A cut off value of 0.19 is suggested. Validation in a prospective trial is needed. No significant financial relationships to disclose.
Clonal selection and double-hit events involving tumor suppressor genes underlie relapse in myeloma
Authors: Niels Weinhold, Cody Ashby, Leo Rasche, Shweta S. Chavan, Caleb Stein, Owen W. Stephens, Ruslana Tytarenko, Michael A. Bauer, Tobias Meissner, Shayu Deshpande, Purvi H. Patel, Timea Buzder, Gabor Molnar, Erich A. Peterson, Frits van Rhee, Maurizio Zangari, Sharmilan Thanendrarajan, Carolina Schinke, Erming Tian, Joshua Epstein, Bart Barlogie, Faith E. Davies, Christoph J. Heuck, Brian A Walker, Gareth J. Morgan
Journal: Blood (2016)
Prospective Study of Treatment Pattern, Effectiveness, and Safety of Zoledronic Acid (ZOL) Therapy Beyond 24 Months in Patients (PTS) with Multiple Myeloma (MM) or Solid Tumor Bone Metastasis (STM)
Authors: T. van den Wyngaert, M. Delforge, C. Doyen, L. Duck, K. Wouters, I. Delabaye, C. Wouters, H. Wildiers
Journal: Annals of Oncology (2012)
Quantitative proteomic analysis of HER2 expression in the selection of gastric cancer patients for trastuzumab treatment
Authors: E. An, C.-Y. Ock, T.-Y. Kim, K.-H. Lee, S.-W. Han, S.-A. Im, T.-Y. Kim, W.-L. Liao, F. Cecchi, A. Blackler, S. Thyparambil, W.H. Kim, J. Burrows, T. Hembrough, D.V.T. Catenacci, D.-Y. Oh, Y.-J. Bang
Journal: Annals of Oncology (2016)

A wide range of response rates have been reported in HER2-positive gastric cancer (GC) patients treated with trastuzumab. Other HER2-targeted therapies for GC have yet to show efficacy in clinical trials. These findings raise question about the ability of standard HER2 diagnostics to accurately distinguish between GC patients who would and would not benefit from anti-HER2 therapies.GC patients (n = 237), including a subset from the Trastuzumab in GC (ToGA) trial were divided into three groups based on HER2 status and history of treatment with standard chemotherapy or chemotherapy plus trastuzumab. We applied mass spectrometry-based proteomic analysis to quantify HER2 protein expression in formalin-fixed tumor samples. Using HER2 expression as a continuous variable, we defined a predictive protein level cutoff to identify which patients would benefit from trastuzumab. We compared quantitated protein level with clinical outcome and HER2 status as determined by conventional HER2 diagnostics.Quantitative proteomics detected a 115-fold range of HER2 protein expression among patients diagnosed as HER2 positive by standard methods. A protein level of 1825 amol/µg was predicted to determine benefit from the addition of trastuzumab to chemotherapy. Trastuzumab treated patients with HER2 protein levels above this cutoff had twice the median overall survival (OS) of their counterparts below the cutoff (35.0 versus 17.5 months, P = 0.011). Conversely, trastuzumab-treated patients with HER2 levels below the cutoff had outcomes similar to HER2-positive patients treated with chemotherapy. (Progression-free survival = 7.0 versus 6.5 months: P = 0.504; OS = 17.5 versus 12.6 months: P = 0.520). HER2 levels were not prognostic for response to chemotherapy.Proteomic analysis of HER2 expression demonstrated a quantitative cutoff that improves selection of GC patients for trastuzumab as compared with current diagnostic methods.
Use of PET to assess tumor metabolism and blood flow by tumor subtype in locally advanced breast cancer.
Authors: S. K. Montgomery, B. F. Kurland, L. K. Dunnwald, R. K. Doot, R. B. Livingston, K. H. Allison, E. K. Schubert, D. A. Mankoff, J. M. Specht
Journal: Journal of Clinical Oncology (2010)

600 Background: Dynamic positron emission tomography (PET) imaging can identify patterns of breast cancer metabolism and perfusion in patients receiving neoadjuvant chemotherapy (NC) that are predictive of response. This analysis examines tumor metabolism and perfusion by tumor subtype. Methods: Tumor subtype was defined by immunohistochemistry (IHC) in 71 patients with locally advanced breast cancer (LABC) undergoing NC. Subtype was defined as luminal (ER/PR positive), triple-negative (TN; ER/PR negative, HER2 normal) and HER2 (ER/PR negative, HER2 over-expressing). Metabolic rate (MRFDG) and blood flow (BF) were calculated from PET imaging prior to NC. Pathologic complete response (pCR) to NC was classified as pCR versus other. Results: Twenty-five (35%) of 71 patients had TN tumors, 6 (8%) were HER2 and 40 (56%) were luminal. MRFDG for TN tumors was on average 67% greater than for luminal tumors (95% CI 9%-156%), and average MRFDG/BF ratio was 53% greater in TN compared to luminal tumors (95% CI 9%-114%) (p < 0.05 for both). Average blood flow levels did not differ by subtype (p = 0.73). Most luminal tumors showed relatively low MRFDG and BF (and did not achieve pCR); high MRFDG was generally matched with high BF in luminal tumors, and predicted pCR. For the TN subtype, pCR was not associated with MRFDG (p = 0.38), BF (p = 0.75), or the MRFDG/BF ratio (p = 0.19). Mismatch between MRFDG and BF was more common in the TN tumors. Conclusions: The relationship between breast tumor metabolism and perfusion differed by subtype. The high MRFDG/BF ratio that predicts poor response to NC was more common in TN tumors. Metabolism and perfusion measures may identify subsets of tumors susceptible and resistant to NC and may help direct targeted therapy. No significant financial relationships to disclose.
The influence of atrial fibrillation on prognosis in mild to moderate heart failure : the V-HeFT studies
Authors: Peter E. Carson, Gary R. Johnson, W. Bruce Dunkman, Ross D. Fletcher, Laura Farrell, Jay N. Cohn
Journal: Circulation (1993)

Background. Atrial fibrillation occurs commonly in heart failure; however, its importance in terins of prognosis is controversial. Methods and Results. We assessed the relation of atrial fibrillation on first Holter monitor to morbidity and mortality in mild to moderate heart failure in 632 patients in the Veterans Affairs Vasodilator-Heart Failure Trial (V-HeFT) I and 795 patients in V-HeFT II. Ninety-nine patients in atrial fibrillation and 533 patients in sinus rhythm were followed for a mean of 2.5 years (range, 6 months to 5.7 years) in V-HeFT I; 107 patients in atrial fibrillation and 688 patients in sinus rhythm in V-HeFT II were followed for a mean of 2.5 years (range, 6 months to 5.0 years)
CBM-10LEUCINE-RICH-ALPHA-2-GLYCOPROTEIN 1(LRG1) LEVELS IN BRAIN TUMORS
Authors: Akihide Kondo, Yuzaburo Shimizu, Mario Suzuki, Masakazu Miyajima, Hajime Arai
Journal: Neuro-Oncology (2015)

Recent studies showed leucine-rich-alpha-2-glycoprotein 1(LRG1) is associated with multiple malignancies. They reported that the silencing of this protein could enhance migration and invasion of tumor cells in vitro, however underlying roles of this protein in tumor biology are still unknown. Then, we studied the expression level of LRG1 in brain tumors and serum in brain tumor-bearing animals. We inoculated KT-3 cells, mouse glioma cell line, into the striatum of C57BL mouse and sacrificed animals at the day 5, 10, and 14 days after the inoculation day. The expression level of LRG1 were evaluated with quantitative real-time PCR and immunohistochemical staining and the serum level of LRG1 were also studied with enzyme-linked immunosorbent assay (ELISA). We revealed that the serum level of LRG1 in brain tumor-bearing animals was relatively high when compared with no brain tumor-bearing animals and the expression of LRG1 in tumors were related to the time course of tumor growing. To the best of our knowledge, our study is one of the first studies reporting the expression data of LRG1 in tumors and the level in serum in tumor-bearing animals.
Global reperfusion therapy in acute myocardial infarction - 1999 to 2004: We're getting better, but we have a long way to go. The Global Registry of Acute Coronary Events
Authors: KA Eagle, RH Mehta, BK Nallamothu, CB Granger, PG Steg, Frans Van de Werf, J Lopez-Sendon, SG Goodman, J Allegrone, KA Fox
Journal: Circulation (2005)
Clinical needs of patients referred early to supportive and palliative care.
Authors: Jung Hye Kwon, David Hui, Caroline Ann Ha, Gary B. Chisholm, Sriram Yennurajalingam, Jung Hun Kang, Eduardo Bruera
Journal: Journal of Clinical Oncology (2012)

9065 Background: Palliative care is evolving from delivering care to patients at the end-of-life to those earlier in the disease trajectory. We evaluated the differences in clinical characteristics, symptoms burdens, and service utilization between traditional palliative care patients (late referrals, LR) and the new patients group who are in earlier in their course of disease (early referrals, ER). Methods: We reviewed consecutive cancer patients referred to the Supportive Care Clinic with follow up visit within 30 days between August 2008 and October 2010. Patients were divided into two groups: ER (defined as patients with expected survival ≥ 2 years or receiving treatment for curative intent) and LR (all others). We compared clinical characteristics, symptoms and service utilization between both groups using chi-square test and Wilcoxon rank sum test. Results: 58% (695/1208) patients had a 2 nd visit within 30 days. Among them, 100 patients were classified as ER (14.4%) and 100/595 LR were randomly selected as the comparison group. ER patients were younger (median age 54 years vs 60 years, p=0.009), more likely to have head and neck cancer (67% vs 6%, p&lt;0.001) and to have a shorter interval between cancer diagnosis and palliative care consultation (3.8 m vs 16.2 m, &lt;0.001). ER patients were also more likely to be CAGE positive (15% vs 4%, p=.014), referred from radiation oncology (49% vs 3%, p&lt;0.001), referred for treatment related side effects (70% vs 9%, p&lt;0.001), and receiving active anti-cancer treatment at the time of consultation (74% vs 48%, p=0.0002). Baseline symptoms (Edmonton Symptom Assessment Scale) were similar between ER and LR except for insomnia (1.8 vs 2, p=0.004). LR patients experienced greater improvement in the symptom distress score (-5.5 vs -3, p=0.007). Overall median number of medical visits was 24 for ER vs 10.5 for LR (p&lt;0.001); however, median visit per month was 4.3 for LR and 2.1 for ER (p&lt;0.001). Conclusions: ER was associated with different patient characteristics; patients have similar distress but different needs and outcomes as compared to traditional LR patients.