tbuckley/cabot-search huggingface dataset:
Evolution of functional capacity and health status 2 years after a pulmonary rehabilitation programme
Authors: Vanda Areias, Dalila Ferreira, Ana Martins, Isabel Matias, Flávia Negrinho, Fátima Rodrigues
Journal: European Respiratory Journal (2012)

Background:  Pulmonary rehabilitation programs (PRP) have been shown to improve exercise capacity and health status and to reduce dyspnoea and healthcare resources use, in patients (pts) with chronic lung disease. These benefits have been shown to last for up to 9 months, however appear to decline by 12 months.   Aim : Evaluate functional exercise capacity and health status after PRP in pts followed in “respiratory failure day hospital”.   Methods:  Retrospective study of pts integrated in a PRP. After PRP, pts who kept a physically active lifestyle (at least 3 walks of 30 minutes/week) were included in the active group (AG). The others were considered as control group (CG). Were analyzed demographic characteristics, pulmonary pathology, six-minute walk test (6MWT) and St. George9s respiratory questionnaire (SGRQ).   Results:  Thirty-two pts were included, 24 in the AG and 8 in the CG. 81% of the pts had chronic obstructive pulmonary disease, with mean FEV 1  of 42%.  Immediately after PRP, there was a significant improvement in the 6MWD and SGRQ global score, in both groups. After completing PRP, there was a decline in the mean 6MWD when evaluated at 6 months, 1 and 2 years as well as in SGRQ score. However, after 2 years, the AG continued to show an average improvement of 32m in the 6MWD and at least 4 points in SGRQ comparing with pre-PRP, although in the CG, there was a clinically significant decline in 6MWD (-34m) and SGRQ score (13 points).   Conclusion:  Despite the progressive decrease of benefits after completing PRP in the AG, these are still significantly positive 2 years after training, which does not happen in the CG. Active lifestyle seems to contribute to maintain the benefits of PRP.
Phase I study of BAY 73–4506, an inhibitor of oncogenic and angiogenic kinases, in patients with advanced solid tumors: Final results of a dose-escalation study
Authors: A. Frost, M. Buechert, C. Unger, O. Christensen, A. Wagner, R. A. Heinig, M. E. Scheulen, D. Strumberg, U. Fasol, K. Mross
Journal: Journal of Clinical Oncology (2008)

2558 Background: BAY 73–4506 is a potent inhibitor of the receptors of tyrosine kinases (VEGFR, KIT, RET, FGFR and PDGFR) and serine/threonine kinases (RAF and p38MAPK). In tumor xenograft models, BAY 73–4506 demonstrated a broad spectrum antitumor activity. Methods: This phase I study was a dose-escalation trial investigating the safety, pharmacokinetic (PK), and pharmacodynamic (PD) profile of BAY 73–4506, given orally in 21 days on/7 days off cycles, until discontinuation due to toxicity or tumor progression. PK was assessed on days 1 and 21 of cycle 1. PD markers including DCE-MRI, soluble VEGFR-2 (sVEGFR-2) and VEGF plasma levels were assessed at each cycle. Tumor response was evaluated as per RECIST. Results: 52 patients (pts) with solid tumors and progressive disease were enrolled and treated with doses of 10 to 220 mg once daily. Frequent tumor types included CRC (31%), malignant melanoma (10%), and ovarian cancer (10%). The median treatment duration was 49.5 days (min. 3, max. 609). Drug-related adverse events (AEs) of all grades reported in >20% of pts were hoarseness (54%), dermatological toxicities (50%; CTC 3–4: 13%), mucositis (35%), diarrhea (25%; CTC 3: 2%), fatigue (23%; CTC 3: 2%), and hypertension (23%; CTC 3: 6%). Treatment-related AEs leading to dose reduction, interruption or discontinuation were hand foot skin reaction (15%), diarrhea (8%), and thrombopenia (6%). BAY 73–4506 showed dose-dependent increase in exposure up to 160 mg where it reached a plateau. The major metabolites (active in vitro and in vivo) also showed dose-dependent increases in exposure up to 220 mg and reached similar AUC(0–24)ss to the parent drug at 220 mg. Of the 33 evaluable pts, 9% achieved a partial response (PR), 64% had stable disease (SD), at least 7 weeks after start of treatment, and 48% had SD or PR for more than 11 weeks. Decrease in sVEGFR-2 level or iAUC60s of Gd-DTPA by DCE-MRI correlated with drug exposure. Conclusions: The recommended phase II dose for BAY 73–4506 is 160 mg daily, using the 21 days on/7 days off treatment schedule. Clinical activity (PR+SD) has been demonstrated in 73% of the evaluable pts. An extension cohort (dose level 160 mg) has been started. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bayer Bayer Bayer Bayer Bayer Bayer
Influence of Inducers of Monooxygenases on Cytotoxic Efficiency of Ellipticine on Leukemia L1210 Cells&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: P Lesca, B Monsarrat, S Cros, C Paoletti
Journal: JNCI Journal of the National Cancer Institute (1981)

The effects of some inducers of microsomal cytochrome P450-dependent monooxygenases on the metabolic bioactivation and the cytotoxicity of the antitumoral drug ellipticine (ELPT) were studied. Rate of growth of leukemia L1210 cells was measured in vitro in the absence and presence of ELPT or measured when the ELPT was metabolically transformed by noninbred Sprague-Dawley rat liver microsomes. The animals used were either untreated or pretreated by various inducers such as phenobarbital, 3-methylcholanthrene, beta-naphthoflavone, 2,3,7,8-tetrachlorodibenzo-p-dioxin, Aroclor 1254, or ELPT. The transformation of ELPT into its two main metabolites, 9-hydroxyellipticine (9-OHE) and 7-hydroxyellipticine, was studied and measured by high-pressure liquid chromatography in conjunction with the determination of cytotoxic activity. A large variability was observed in the bioactivation and cytotoxic efficiency of ELPT mediated by the different microsomal preparations: The more P448 and/or P1-450 forms of cytochrome were induced, the more the 9-OHE was produced and the more the cytotoxicity toward L1210 cells was enhanced. These features were compared with those elicited by the activation of cyclophosphamide, which was transformed into cytotoxic metabolites by the cytochrome P450 form specifically induced by phenobarbital-type inducers.
Combating climate change
Authors: N. Watts, R. Stott, A. M. Rafferty
Journal: BMJ (2015)

Health professional bodies unite for a fairer and healthier world

The second half of the 20th century brought renewed understanding of the links between human wellbeing and environmental systems. In 1988 the United Nations formed the Intergovernmental Panel on Climate Change (IPCC), charged with documenting the effects of climate change and formulating realistic strategies for action. Its first report led to the UN Framework Convention on Climate Change (UNFCCC) in 1992. Unfortunately, since then neither humanity nor the planet have fared well. The Stockholm Resilience Centre has identified nine planetary boundaries within which humanity can develop and continue to thrive,1 and we have already crossed five. These are extinction rates, greenhouse gas emissions, change in land use, phosphorous and nitrogen cycles, and ocean acidification. In addition, we are pushing at the limits of three more—fresh water supply, air pollution, and novel pollutants.

The evidence of adverse effects is incontrovertible, as is the need for urgent action. More frequent and more severe natural disasters, instability in food and water supply, the spread of infectious disease, and forced migration are already affecting human health and provide a …
Results of first-line weekly paclitaxel (P) + gemcitabine (G) in metastatic breast cancer (MBC): An AERO phase II trial
Authors: M. Mousseau, D. Serin, T. Petit, F. Priou, L. Zelek
Journal: Journal of Clinical Oncology (2007)

1103 Background: Three weekly paclitaxel and gemcitabine (PG) combination is recognised as an efficient treatment of metastatic breast cancer. Weekly paclitaxel has shown improved results comparatively with the three weekly administration. We conducted a study to evaluate a weekly schedule of PG combination in fist line treatment of metastatic breast cancer (MBC). Patients and methods: Patients with MBC were enrolled in this study to evaluate the feasibility and efficacy of P 80mg/m 2 D1, 8, 15 and G 1,250 mg/m 2 D1, 8 (at fixed dose rate of 10mg/m 2 /min) and cycles were repeated every 21 days. This phase II trial had a 2 stages design. Overall response rate was the primary end point. Results: In the first step of the trial 19 pts were enrolled with a median age of 59.5 (range 40 - 74). Baseline ECOG &lt; 2 in 89% of pts. Main metastatic sites were: bone (36 %), lung (36%), liver (36%) and lymph nodes (32%). 52 % of pts had only one metastatic site. Previous treatments included surgery (89%), radiotherapy (73%), anthracycline based chemotherapy (74%) and adjuvant hormontherapy (52%). 18 pts were evaluable for efficacy and toxicity. 6 achieved PR, 5 SD and 6 PD resulting in an ORR of 33%. All patients were evaluable for toxicity. Main grade 3–4 toxicities per patient were neutropenia (67%), febrile neutropenia (5%), anemia (17%), thrombocytopenia (33%), trasnsaminases leveations (11%) and dyspnia (5%). Chemotherapy was delayed frequently for toxicity reasons (delays or arrest for toxicity in 15 pts). Conclusion: This weekly PG regimen has some activity in MBC. Although life-threatening toxicities were uncommon, delays in haematological recovery are frequent, making the investigated schedule unsuitable for further studies. [Table: see text]
GANEing traction: The broad applicability of NE hotspots to diverse cognitive and arousal phenomena
Authors: Mara Mather, David Clewett, Michiko Sakaki, Carolyn W. Harley
Journal: Behavioral and Brain Sciences (2016)

The GANE (glutamate amplifies noradrenergic effects) model proposes that local glutamate-norepinephrine interactions enable "winner-take-more" effects in perception and memory under arousal. A diverse range of commentaries addressed both the nature of this "hotspot" feedback mechanism and its implications in a variety of psychological domains, inspiring exciting avenues for future research.
Leukocyte Groups and Acute Leukemia&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: F. M. Kourilsky, J. Dausset, N. Feingold, J. M. Dupuy, Jean Bernard
Journal: JNCI Journal of the National Cancer Institute (1968)

The frequency and the distribution of 10 leukoplatelet antigens of the HL-A system [the designation “HU-1 system” has been changed to “HL-A” (Histocompatibility Testing, Munksgaard, Copenhagen, 1967)] were determined on the leukocytes and platelets of 116 patients with acute leukemia in remission. These were compared with those observed in 234 nonleukemic individuals. No significant difference was noted between these two groups. The reactivity to cytotoxic immune sera of the lymphocytes of the patients in longer remission appears weaker than that of nonleukemic individuals.
Lessons learned from two decades of sentinel node biopsies for melanoma
Authors: R. P. Scheri, M. Kavanagh, L. Wanek, R. Essner, D. Morton
Journal: Journal of Clinical Oncology (2006)

8055 Background: The long term prognosis for patients with melanoma staged by sentinel node biopsy (SNB) remains unclear, largely due to limited follow-up from a variety of small single institution studies. We evaluated our extensive 20-year experience to evaluate the long term prognostic significance of SNB. Methods: We retrospectively reviewed the records of 2001 successive patients who underwent LM/SNB at our center from 1985 until 2004. After preoperative lymphoscintigraphy, blue dye and a hand-held gamma probe were used for intraoperative identification of sentinel nodes (SN). SN were evaluated for metastases by hemotoxylin and eosin and immunohistochemical staining with HMB45, S-100, and more recently with antibodies to melanA. Patients with tumor-positive SN underwent completion dissection (SCLND). Clinicopathological features of the patients, primaries and SN status were evaluated for their influence on survival using multivariate Cox regression analysis. Results: After median follow-up of 49 months (range 1–237). Median age for our patients was 51 years (range 10–91). Of the 2,001 patients, 1584 (79%) had tumor-negative and 417 (21%) had tumor-positive SN. Survival rates were higher in patients with tumor-negative vs. tumor-positive SN (91 + 2% vs. 72 + 5% at 5 years, log-rank p&lt;0.0001; and 84 + 3% vs. 64 + 7% at 10 years, log-rank p&lt;0.0001). Of the 417 patients with SN metastases, 293 (70%) had a single tumor-positive node, 101 (24%) had 2–3 positive nodes, and 25 (6%) had at least 4 positive nodes (sentinel plus nonsentinel). Overall survival was significantly better when metastases were confined to single vs. multiple nodes (77 + 3% vs. 63 + 5%; p=0.0017). Multivariate analysis with Cox regression identified SN status (p&lt;0.0001) as the most important prognostic factor, Hazard Ratio 3.44 (2.47–4.79). Breslow thickness (p&lt;0.0001) and ulceration (p=0.0001) are also independently significant for survival. Gender and primary site were not significant. Conclusions: Our results demonstrate the long term prognostic significance of SN status. LM/SNB should become standard of care for primary melanoma because it is the most accurate factor for the quantification of the risk for recurrence and death available. No significant financial relationships to disclose.
Glycosaminoglycan Production and Distribution in Cloned B16 Murine Melanoma Cell Lines Exhibiting Different Lung Colony-Forming Efficiencies&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: C A Maniglia, J J Gomez, S D Luikart, A C Sartorelli
Journal: JNCI Journal of the National Cancer Institute (1985)

Three cloned B16 murine melanoma cell lines were characterized with respect to their ability to a) detach from a plastic tissue culture substratum, b) form experimental pulmonary metastases, and c) produce and process glycosaminoglycans (GAGS). All three of the cell lines formed pulmonary metastases to different extents. Chondroitin sulfate and heparin-heparan sulfate were the major GAGS produced by all of the clones. Although the major compositional analyses of the cell lines were similar, some differences were apparent. The clone never selected for lung colony-forming efficiency and with the lowest metastatic potential (B16YL1) exhibited a reduced cell-associated glycosaminoglycan (GAG) matrix, shed the highest proportion of labeled GAGS into the medium, and was the most easily removed from the tissue culture substratum. In contrast, the other two cell lines (B16YM1 and B16YH1), derived from cultures selected for lung colony-forming efficiency, exhibited GAG-enriched cellular coats and were more resistant to EDTA-induced detachment from the plastic substratum. Both the B16YL1 and B16YM1 clones, which exhibited the lowest lung colony-forming efficiencies, shed an unsulfated chondroitin species into the extracellular fraction that was not evident in the most metastatic clone B16YH1. Despite these differences, cellular GAG matrix development and detachment from the plastic substratum showed only a partial correlation with lung colony-forming efficiency, presumably expressing the complexity of this biological phenomenon. Nonetheless, the findings suggest that GAGS may play an important role at several steps along the cascade of events leading to the successful dissemination of malignant cells.
Carbonic anhydrase IX (CA IX) as a predictive marker for benefit from post-mastectomy adjuvant locoregional radiation (RT): Results from the British Columbia (BC) Randomized Radiation Trial
Authors: S. Chia, J. Ragaz, N. Makretsov, M. Cheang, M. Hayes, B. Gilks, A. Harris, J. Spinelli, K. Gelmon, I. Olivotto, D. Huntsman
Journal: Journal of Clinical Oncology (2005)

571 Background: The benefit of adjuvant locoregional RT in post-mastectomy node positive breast cancer is controversial. Three randomized trials (Danish Breast Cancer Cooperative Group 82b/82c Trials and the BC Randomized Radiation Trial) have demonstrated improved survival for the addition of locoregional RT. We have previously shown in a large population based tissue microarray (TMA) series that CA IX, a hypoxia regulated enzyme, is an independent poor prognostic factor. We now investigated whether CA IX would be a predictive marker for locoregional RT in the context of the BC Randomized Radiation Trial. Methods: A TMA series was constructed from 160 available blocks out of the 318 patients randomized on the trial. CA IX expression was evaluated by IHC with a monclonal antibody M75. Any staining for CA IX within tumour cells was scored as positive. The frequency of expression of CA IX and its association with other standard prognostic factors (tumour size, grade, ER, PR, HER-2) as well as other biological correlates (p53, EGFR) was evaluated. Statistical analysis included KM survival analysis and interaction tests. Results: Median follow-up of the trial is greater than 15 years. CA IX was expressed in 23% of cases. In the patients randomized to no RT, CA IX is a poor prognostic marker associated with a worse overall survival (log rank p=0.0002). CA IX expression was predictive of benefit to locoregional RT. In the CA IX positive cohort those patients randomized to RT had significantly improved survival (p<0.0005) with an estimated 15 year overall survival of 73% with RT versus 19% without RT. Conversely in the CA IX negative cohort there was no significant benefit for the addition of RT (p=0.225). The associated 15 year overall survival was 54% and 50% with and without RT respectively. The interaction test between CA IX expression and RT was significant (p<0.01). Conclusions: CA IX appears to be a promising biomarker predictive of benefit for locoregional RT. Further work validating this is warranted. Work is ongoing assessing for the biological rationale (e.g. BNIP3, HIF1α) and other biologic correlates associated with CA IX expression. No significant financial relationships to disclose.
Influence of Dose and Age on the Induction of Malignant Lymphomas and Other Tumors by 7,12-Dimethylbenz[α]anthracene in Swiss Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Bela Toth, Henry Rappaport, Philippe Shubik
Journal: JNCI Journal of the National Cancer Institute (1963)

In Swiss mice receiving a single subcutaneous injection of 7,12-dimethylbenz[α]anthracene (DMBA) at birth there is a dose level at which the carcinogen induces a high incidence of malignant lymphomas. Increasing the dose above this level shortens the latent period. Newborn animals are more susceptible to this leukemogenic effect of DMBA than animals 2 to 4 weeks old. The malignant lymphomas observed under our experimental conditions were either of the undifferentiated (stem cell) type or showed varying types of differentiation that were lymphocytic, histiocytic, or both. Malignant lymphomas of the stem cell type were thymic in origin, occurred below the age of 35 weeks, and were found only in carcinogen-treated animals. They were a uniform group of tumors grossly, cytologically, and biologically. In contrast, the more differentiated malignant lymphomas represented a heterogeneous group of neoplasms of several types, the majority of which were not primary in the thymus. They occurred above the age of 35 weeks in both untreated and carcinogen-treated mice. The incidence of subcutaneous sarcomas at the site of injection increased with larger dose and advancing age. The coexistence of sarcoma at the site of injection and malignant lymphoma was rare at any age group under our experimental conditions.—J Nat Cancer Inst 30: 723–741, 1963.
Safety of Propranolol Therapy for Severe Infantile Hemangioma
Authors: Sorilla Prey, Jean-Jacques Voisard, Alain Delarue, Geneviève Lebbe, Alain Taïeb, Christine Leaute-Labreze, Khaled Ezzedine
Journal: JAMA (2016)

This study uses data collected between April 2010 and April 2013 to assess the safety of propranolol for severe infantile hemangioma in children given this therapy under the French Health Products Agency compassionate use program.
Some Unusual Complications of Malignancies
Authors: Yi-Hong Chou, Hong-Jen Chiou, Chui-Mei Tiu, Jen-Dar Chen, Guo-Shian Hung, Jen-Hwei Chiang
Journal: Journal of Clinical Oncology (2002)

Article Tools DIAGNOSIS IN ONCOLOGY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.20.19.4108 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12351607 Some Unusual Complications of Malignancies Case 1. Spontaneous Rupture of Hepatocellular Carcinoma Demonstrated by Contrast-Enhanced Sonography Yi-Hong ChouxYi-Hong ChouSearch for articles by this author , Hong-Jen ChiouxHong-Jen ChiouSearch for articles by this author , Chui-Mei TiuxChui-Mei TiuSearch for articles by this author , Jen-Dar ChenxJen-Dar ChenSearch for articles by this author , Guo-Shian HungxGuo-Shian HungSearch for articles by this author , Jen-Hwei ChiangxJen-Hwei ChiangSearch for articles by this author Show More Veterans General Hospital–Taipei and School of Medicine and Institute of Biomedical Engineering, National Yang Ming University, Taipei, Taiwan https://doi.org/10.1200/JCO.2002.20.19.4108 First Page Full Text PDF Figures and Tables © 2002 by American Society of Clinical Oncology
Autologous tumor-lysate pulsed dendritic cell vaccination, together with the TLR-7 agonist 5% imiquimod, and serum pro- inflammatory cytokine levels in glioblastoma patients
Authors: R. M. Prins, S. Odesa, H. Soto, W. H. Yong, A. Lai, M. Bosch, A. Boynton, T. F. Cloughesy, L. M. Liau
Journal: Journal of Clinical Oncology (2008)

11021 Background: Standard therapy for glioblastoma, which includes surgery followed by radiation and concurrent chemotherapy, creates a low tumor burden environment that could be ideal for immunotherapeutic approaches. We conducted a Phase I study to assess the safety and immunologic responses of tumor lysate-pulsed dendritic cell (DC) therapy plus topical imiquimod, in combination with standard radio-chemotherapy. Methods: Thirteen patients with newly diagnosed glioblastoma were immunized using autologous tumor lysate-pulsed DC at 2-week intervals, following completion of radio-chemotherapy. The primary clinical endpoint was 2-year survival. Patients without tumor progression subsequently received booster vaccinations combined with topical administration of the TLR-7 agonist, imiquimod. Immunologic responses to tumor antigens were monitored by tetramer staining and intracellular cytokine staining. Measurement of serum cytokine levels (TH1/TH2: IFN-γ, TNF-α, IL-2, IL-4, IL-6, IL-10) was performed using cytometric bead arrays (CBA). Global gene expression profiling was also performed on pre-treatment tumor samples. Results: All immunizations were well tolerated, with only mild side effects attributable to the DC vaccination and imiquimod adjuvant. Increased levels of CD8+ T cells reactive against tumor antigens, (e.g., gp100, TRP-2, her-2, survivin, and CMV antigens), were detected in 5 patients. CBA measurement of serum cytokine levels revealed small, but detectable levels of TNF-α following the initial DC vaccination. Robust increases in serum TNF-α and IL-6 were observed after booster vaccinations, temporally correlating with imiquimod administration. Clinically, 8 of the 13 patients have progressed, and 6 of those have died. The median PFS to date is 13.9 mos. and median OS is 33.8 mos. This compares favorably to the published literature, with a median PFS of 6.9 mos and OS of 14.6 mos. Conclusions: This study demonstrates the safety and clinical/immunologic effects of an autologous tumor lysate-pulsed DC vaccine for patients with newly diagnosed glioblastoma. Serum TNFα responses may portend therapeutic anti-tumor immune responses to DC vaccination. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Northwest Biotherapeutics, Inc. Northwest Biotherapeutics, Inc. Northwest Biotherapeutics, Inc.