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  • 1
    Online Resource
    Online Resource
    Three-year Safety of Radium-223 Dichloride in Patients with Castration-resistant Prostate Cancer and Symptomatic Bone Metastases from Phase 3 Randomized Alpharadin in Symptomatic Prostate Cancer Trial
    Elsevier BV ; 2018
    In:  European Urology Vol. 73, No. 3 ( 2018-03), p. 427-435
    Details
    In: European Urology, Elsevier BV, Vol. 73, No. 3 ( 2018-03), p. 427-435
    Type of Medium: Online Resource
    ISSN: 0302-2838
    URL: Article
    DOI: 10.1016/j.eururo.2017.06.021
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2018
    detail.hit.zdb_id: 1482253-2
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  • 2
    Online Resource
    Online Resource
    Associations between AI-Assisted Tumor Amphiregulin and Epiregulin IHC and Outcomes from Anti-EGFR Therapy in the Routine Management of Metastatic Colorectal Cancer
    American Association for Cancer Research (AACR) ; 2023
    In:  Clinical Cancer Research ( 2023-07-13), p. OF1-OF13
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), ( 2023-07-13), p. OF1-OF13
    Abstract: High tumor production of the EGFR ligands, amphiregulin (AREG) and epiregulin (EREG), predicted benefit from anti-EGFR therapy for metastatic colorectal cancer (mCRC) in a retrospective analysis of clinical trial data. Here, AREG/EREG IHC was analyzed in a cohort of patients who received anti-EGFR therapy as part of routine care, including key clinical contexts not investigated in the previous analysis. Experimental Design: Patients who received panitumumab or cetuximab ± chemotherapy for treatment of RAS wild-type mCRC at eight UK cancer centers were eligible. Archival formalin-fixed paraffin-embedded tumor tissue was analyzed for AREG and EREG IHC in six regional laboratories using previously developed artificial intelligence technologies. Primary endpoints were progression-free survival (PFS) and overall survival (OS). Results: A total of 494 of 541 patients (91.3%) had adequate tissue for analysis. A total of 45 were excluded after central extended RAS testing, leaving 449 patients in the primary analysis population. After adjustment for additional prognostic factors, high AREG/EREG expression (n = 360; 80.2%) was associated with significantly prolonged PFS [median: 8.5 vs. 4.4 months; HR, 0.73; 95% confidence interval (CI), 0.56–0.95; P = 0.02] and OS [median: 16.4 vs. 8.9 months; HR, 0.66 95% CI, 0.50–0.86; P = 0.002] . The significant OS benefit was maintained among patients with right primary tumor location (PTL), those receiving cetuximab or panitumumab, those with an oxaliplatin- or irinotecan-based chemotherapy backbone, and those with tumor tissue obtained by biopsy or surgical resection. Conclusions: High tumor AREG/EREG expression was associated with superior survival outcomes from anti-EGFR therapy in mCRC, including in right PTL disease. AREG/EREG IHC assessment could aid therapeutic decisions in routine practice.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1078-0432.CCR-23-0859
    RVK:
    XA 36791
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
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  • 3
    Online Resource
    Online Resource
    ACTIVATED HUMAN NEUTROPHILS EXPRESS VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF)
    Elsevier BV ; 1998
    In:  Cytokine Vol. 10, No. 4 ( 1998-04), p. 254-257
    Details
    In: Cytokine, Elsevier BV, Vol. 10, No. 4 ( 1998-04), p. 254-257
    Type of Medium: Online Resource
    ISSN: 1043-4666
    URL: Article
    DOI: 10.1006/cyto.1997.0297
    Language: English
    Publisher: Elsevier BV
    Publication Date: 1998
    detail.hit.zdb_id: 1463198-2
    SSG: 12
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  • 4
    Online Resource
    Online Resource
    1.5-year post-treatment follow-up of radium-223 dichloride (Ra-223) in patients with castration-resistant prostate cancer (CRPC) and bone metastases from the phase 3 ALSYMPCA study.
    American Society of Clinical Oncology (ASCO) ; 2014
    In:  Journal of Clinical Oncology Vol. 32, No. 4_suppl ( 2014-02-01), p. 9-9
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 32, No. 4_suppl ( 2014-02-01), p. 9-9
    Abstract: 9 Background: Ra-223 is a first-in-class alpha-emitting pharmaceutical recently Food and Drug Administration approved for treatment (tx) of patients (pts) with CRPC and symptomatic bone metastases (mets). In ALSYMPCA, Ra-223 significantly improved overall survival by 3.6 months versus placebo (pbo) (HR = 0.70; 95% CI, 0.58-0.83; P 〈 0.001) and was well tolerated. Reported here are long-term safety data ~1.5 years after the last pt’s final injection (inj) from the entire ALSYMPCA safety population. Methods: Eligible pts had progressive CRPC with ≥ 2 symptomatic bone mets and no known visceral mets, were receiving best standard of care, and had received docetaxel or were unfit for or declined docetaxel. Pts were randomized 2:1 to 6 inj of Ra-223 (50 kBq/kg IV; q 4 wk) or matching pbo. Only adverse events (AEs) considered tx related by the investigator were reported during follow-up. Long-term safety data were assessed by specific diseases, including acute myelogenous leukemia, myelodysplastic syndrome, aplastic anemia, primary bone cancer, or primary cancer in other organs. Results: ALSYMPCA safety population included 901 pts (Ra-223, n = 600; pbo, n = 301). Overall, 25 (4%) Ra-223 and 8 (3%) pbo pts had ≥ 1 tx-related AE (Table). During follow-up, primary cancer in other organs was reported in 5 pts (Ra-223, n = 2; pbo, n = 3). Conclusions: Ra-223 is an effective and well-tolerated tx for CRPC with symptomatic bone mets. No major safety issues were identified within ~1.5 years after tx in the ALSYMPCA safety population. Clinical trial information: NCT00699751. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2014.32.4_suppl.9
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2014
    detail.hit.zdb_id: 2005181-5
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  • 5
    Online Resource
    Online Resource
    Cabazitaxel for metastatic castration-resistant prostate cancer (mCRPC): Final quality-of-life (QOL) results with safety data from the United Kingdom (UK) Early Access Programme (EAP) (NCT01254279).
    American Society of Clinical Oncology (ASCO) ; 2013
    In:  Journal of Clinical Oncology Vol. 31, No. 6_suppl ( 2013-02-20), p. 91-91
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 6_suppl ( 2013-02-20), p. 91-91
    Abstract: 91 Background: Several drugs can now improve survival in mCRPC after docetaxel, including cabazitaxel, a next generation taxane. TROPIC (NCT00417079) showed an overall survival benefit of 2.4 months for cabazitaxel compared with mitoxantrone for mCRPC. The UK EAP provided patients access to cabazitaxel; detailed QOL and safety data were recorded. Interim analysis suggested improvements in QOL, particularly pain scores and a good safety profile. We report final QOL and updated safety data. Methods: 108 patients recruited at 12 centres received cabazitaxel 25mg/m 2 intravenously every 3 weeks with oral prednisolone 10mg daily. EQ-5D questionnaires and health state visual analogue scale (VAS) were completed at baseline, at alternate cycles and at 30 days post treatment. Safety assessments followed each cycle. Results: According to EQ-5D and VAS scores, QOL was stable with an overall trend towards improvement in patients who continued treatment. Paired ‘within patient’ analyses also support this trend. Improved pain was noted more frequently than deterioration at all time points and pain scores were at least stable in 96% of patients at cycle 10. A median of 6 cycles were given. 34 patients (31%) received 10 or more cycles. Grade 3/4 adverse events were uncommon, the most frequent being fatigue (9.3%), diarrhoea (2.8%) and neutropenic sepsis (1.9%). 85% received prophylactic granulocyte colony stimulating factor. Conclusions: Almost 1/3 of patients completed 10 or more cycles in the UK EAP. QOL was stable with trends to improved EQ-5D and VAS scores. Improved or stable pain was observed in the majority of patients continuing therapy. The UK EAP provides the first data on QOL benefit with cabazitaxel in mCRPC post docetaxel and demonstrates manageable toxicity. Final safety data will be available for presentation. Clinical trial information: NCT01254279. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2013.31.6_suppl.91
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
    detail.hit.zdb_id: 2005181-5
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  • 6
    Online Resource
    Online Resource
    Updated analysis of the phase III, double-blind, randomized, multinational study of radium-223 chloride in castration-resistant prostate cancer (CRPC) patients with bone metastases (ALSYMPCA).
    American Society of Clinical Oncology (ASCO) ; 2012
    In:  Journal of Clinical Oncology Vol. 30, No. 18_suppl ( 2012-06-20), p. LBA4512-LBA4512
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 18_suppl ( 2012-06-20), p. LBA4512-LBA4512
    Abstract: LBA4512 Background: Radium-223 chloride (Ra-223), a targeted alpha-emitter, targets bone metastases (mets) with high-energy alpha-particles of short range ( 〈 100 µm). ALSYMPCA, a phase III double-blind, randomized, multinational study, compared Ra-223 plus best standard of care (BSC) vs placebo plus BSC in CRPC patients (pts) with bone mets. In a planned interim analysis (n = 809), based on 314 events, Ra-223 significantly improved overall survival (OS) vs placebo (median 14.0 mo vs 11.2 mo, respectively; HR = .695; 95% CI, .552-.875; 2-sided p = .00185). Secondary endpoints were met and Ra-223 safety was favorable. An updated analysis was conducted prior to the crossover to further assess the effect of Ra-223 on the primary endpoint (OS), secondary endpoints including skeletal-related events (SREs), and safety. Methods: Eligible pts had confirmed symptomatic CRPC with ≥ 2 bone mets; no known visceral mets; and were post-docetaxel, unfit for docetaxel, or had declined docetaxel. Pts were randomized 2:1 to receive 6 injections of Ra-223 (50 kBq/kg IV) q4wks or matching placebo. An updated descriptive analysis of OS, based on 528 events, was performed including data from all randomized pts prior to implementing crossover to Ra-223 for placebo pts. Results: 921 pts (Ra-223, n = 614; placebo, n = 307) were randomized from 6/2008-2/2011. Ra‑223 significantly improved OS vs placebo (median 14.9 mo vs 11.3 mo, respectively; HR = .695; 95% CI, .581-.832; p = 0.00007), and time to first SRE was significantly prolonged (median 15.6 mo vs 9.8 mo, respectively; HR = 0.658; 95% CI, 0.522-0.830; p = 0.00037). Safety and tolerability of Ra-223 remained favorable, with low myelosuppression (e.g., gr 3/4 neutropenia in 2.2% and 0.7% and gr 3/4 thrombocytopenia in 6.3% and 2% of the Ra-223 and placebo groups, respectively). Conclusions: On updated analysis, the median OS benefit for Ra-223 increased from 2.8 to 3.6 months, with a hazard ratio of 0.695 (i.e., 30.5% reduction in risk of death). Ra-223 is an effective therapy that improves OS and time to first SRE with a highly favorable safety profile, and may provide a new standard of care for CRPC pts with bone mets.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2012.30.18_suppl.lba4512
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
    detail.hit.zdb_id: 2005181-5
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  • 7
    Online Resource
    Online Resource
    Impact of Nitrogen and Phosphorus on [ 14 C]Lignocellulose Decomposition by Stream Wood Microflora
    American Society for Microbiology ; 1985
    In:  Applied and Environmental Microbiology Vol. 49, No. 5 ( 1985-05), p. 1113-1118
    Details
    In: Applied and Environmental Microbiology, American Society for Microbiology, Vol. 49, No. 5 ( 1985-05), p. 1113-1118
    Abstract: Nutritional and physical factors affecting the decomposition of [ 14 C]lignocellulose prepared from Douglas fir ( Pseudotsuga menziesii ) were examined by incubating the labeled substrate with homogenized surface wood scrapings obtained from a Douglas fir log in a Pacific Northwest stream. Incubations were conducted in distilled water, in stream water collected from four different sources, or in a defined mineral salts solution with or without supplemental N (KNO 3 ). Decomposition rates of [ 14 C]lignocellulose, as measured by 14 CO 2 evolution, were greater in each of the four filter-sterilized sources of stream water than in distilled water alone. Decomposition experiments conducted in stream water media with the addition of defined mineral salts demonstrated that [ 14 C]cellulose decomposition was stimulated 50% by the addition of either KNO 3 or KH 2 PO 4 /K 2 HPO 4 and further enhanced (167%) by a combination of both. In contrast, [ 14 C]lignin decomposition was stimulated (65%) only by the addition of both N and P. Decomposition of [ 14 C]lignocellulose was greatest when supplemental KNO 3 was supplied in concentrations of at least 10.0 mg of N liter −1 but not increased further by higher concentrations. The decomposition of [ 14 C]lignocellulose increased as the incubation temperature was raised and NO 3 −1 -N supplementation further increased these rates between three-and sevenfold over the range of temperatures examined (5 to 22°C). Accumulation of NH 4 + (2 to 4 mg of N liter −1 ) was always observed in culture filtrates of incubations which had been supplemented with KNO 3 , the quantity being independent of NO 3 − concentrations ≥ 10 mg of N liter −1 . The role of supplemental NO 3 − in the decomposition of [ 14 C]lignocellulose is discussed in relation to wood decomposition and the low concentrations of N found in stream ecosystems of the Pacific Northwest.
    Type of Medium: Online Resource
    ISSN: 0099-2240 , 1098-5336
    URL: Article
    DOI: 10.1128/aem.49.5.1113-1118.1985
    RVK:
    WA 15000
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 1985
    detail.hit.zdb_id: 223011-2
    detail.hit.zdb_id: 1478346-0
    SSG: 12
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  • 8
    Online Resource
    Online Resource
    Nitrogen Dynamics in Stream Wood Samples Incubated with [ 14 C]Lignocellulose and Potassium [ 15 N]Nitrate
    American Society for Microbiology ; 1985
    In:  Applied and Environmental Microbiology Vol. 49, No. 5 ( 1985-05), p. 1119-1123
    Details
    In: Applied and Environmental Microbiology, American Society for Microbiology, Vol. 49, No. 5 ( 1985-05), p. 1119-1123
    Abstract: Surface wood samples obtained from a Douglas fir log ( Pseudotsuga menziesii ) in a Pacific Northwest stream were incubated in vitro with [ 14 C]lignocellulose in a defined mineral salts medium supplemented with 10 mg of N liter −1 of 15 N-labeled NO 3 − (50 atom% 15 N). Evolution of 14 CO 2 , distribution and isotopic dilution of 15 N, filtrate N concentrations, and the rates of denitrification, N 2 fixation, and respiration were measured at 6, 12, and 18 days of incubation. The organic N content of the lignocellulose-wood sample mixture had increased from 132 μg of N to a maximum of 231 μg of N per treatment after 6 days of incubation. Rates of [ 14 C]lignocellulose decomposition were greatest during the first 6 days and then began to decline over the remaining 12 days. Total CO 2 evolution was also highest at day 6 and declined steadily over the remaining duration of the incubation. Filtrate NH 4 + -N increased from background levels to a final value of 57 μg of N per treatment. Filtrate NO 3 − N completely disappeared by day 6, and organic N showed a slight decline between days 12 and 18. The majority of the 15 N that could be recovered appeared in the particulate organic fraction by day 6 (41 μg of N), and the filtrate NH 4 + N fraction contained 11 μg of 15 N by day 18. The 15 N enrichment values of the filtrate NH 4 + and the inorganic N associated with the particulate fraction had increased to approximately 20 atom% 15 N by 18 days of incubation, whereas the particulate organic fraction reached its highest enrichment by day 6. Measurements of N 2 fixation and denitrification indicated an insignificant gain or loss of N from the experimental system by these processes. The data show that woody debris in stream ecosystems might function as a rapid and efficient sink for exogenous N, resulting in stimulation of wood decomposition and subsequent activation of other N cycling processes.
    Type of Medium: Online Resource
    ISSN: 0099-2240 , 1098-5336
    URL: Article
    DOI: 10.1128/aem.49.5.1119-1123.1985
    RVK:
    WA 15000
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 1985
    detail.hit.zdb_id: 223011-2
    detail.hit.zdb_id: 1478346-0
    SSG: 12
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  • 9
    Online Resource
    Online Resource
    Response to the Letter to the Editor by Eberhard et al.
    Springer Science and Business Media LLC ; 2017
    In:  Parasites & Vectors Vol. 10, No. 1 ( 2017-12)
    Details
    In: Parasites & Vectors, Springer Science and Business Media LLC, Vol. 10, No. 1 ( 2017-12)
    Type of Medium: Online Resource
    ISSN: 1756-3305
    URL: Article
    DOI: 10.1186/s13071-017-2125-5
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2017
    detail.hit.zdb_id: 2409480-8
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  • 10
    Online Resource
    Online Resource
    Studies on a single immunoglobulin-binding domain of protein L from Peptostreptococcus magnus: the role of tyrosine-53 in the reaction with human IgG
    Portland Press Ltd. ; 2001
    In:  Biochemical Journal Vol. 353, No. 2 ( 2001-01-15), p. 395-401
    Details
    In: Biochemical Journal, Portland Press Ltd., Vol. 353, No. 2 ( 2001-01-15), p. 395-401
    Abstract: Chemical modification experiments with tetranitromethane (TNM) have been used to investigate the role of tyrosine residues in the formation of the complex between PpL (the single Ig-binding domain of protein L, isolated from P. magnus strain 3316) and the kappa light chain (κ-chain). Reaction of PpL with TNM causes the modification of 1.9 equiv. of tyrosine (Tyr51 and Tyr53) and results in an approx. 140-fold decrease in affinity for human IgG. Similar experiments with mutated PpL proteins suggest that nitration predominantly inactivates the protein by modification of Tyr53. Reduction of the nitrotyrosine groups to aminotyrosine by incubation with sodium hydrosulphite does not restore high affinity for IgG. Modification of κ-chain by TNM resulted in the nitration of 3.1±0.09 tyrosine residues. When the PpLŐκ-chain complex was incubated with TNM, 4.1±0.04 tyrosine residues were nitrated, indicating that one tyrosine residue previously modified by the reagent was protected from TNM when the proteins are in complex with each other. The Kd for the equilibrium between PpL, human IgG and their complex has been shown by ELISA to be 112±20nM. A similar value (153±33nM) was obtained for the complex formed between IgG and the Tyr64 → Trp mutant (Y64W). However, the Kd values for the equilibria involving the PpL mutants Y53F and Y53F,Y64W were found to be 3.2±0.2 and 4.6±1µM respectively. These suggest that the phenol group of Tyr53 in PpL is important to the stability of the PpLŐκ-chain complex.
    Type of Medium: Online Resource
    ISSN: 0264-6021 , 1470-8728
    URL: Article
    DOI: 10.1042/bj3530395
    RVK:
    WA 15000
    Language: English
    Publisher: Portland Press Ltd.
    Publication Date: 2001
    detail.hit.zdb_id: 1473095-9
    SSG: 12
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