215 research outputs found
Multicenter randomized phase III trial of Epirubicin plus Paclitaxel vs Epirubicin followed by Paclitaxel in metastatic breast cancer patients: focus on cardiac safety
The aim of the study was to evaluate cardiac safety of two different schedules of Epirubicin and Paclitaxel in advanced breast cancer patients enrolled into a multicenter randomized phase III trial. Patients received Epirubicin 90 mgm(-2) plus Paclitaxel 200 mgm(-2) (3-h infusion) on day 1 every 3 weeks for eight courses (arm A), or Epirubicin 120 mgm(-2) on day 1 every 3 weeks for four courses followed by four courses of Paclitaxel 250 mgm(-2) on day 1 every 3 weeks (arm B). Left ventricular ejection fraction was evaluated by bidimesional echocardiography at baseline, after four and eight courses of chemotherapy and every 4 months during follow-up. Baseline median left ventricular ejection fraction was 60% in arm A and 65% in arm B; after four courses, figures were 57 and 60%, respectively. After eight courses, the median left ventricular ejection fraction in arm A declined to 50% while no further reduction was detected in arm B by adding four courses of high-dose Paclitaxel. Seven episodes of congestive heart failure were observed during treatment in arm A. Present monitoring demonstrated that the risk of congestive heart failure or impairment in the cardiac function correlated only with the cumulative dose of Epirubicin; no impact on cardiotoxicity can be attributed to high-dose Paclitaxel
The Results of CHD7 Analysis in Clinically Well-Characterized Patients with Kallmann Syndrome
Item does not contain fulltextCONTEXT: Kallmann syndrome (KS) and CHARGE syndrome are rare heritable disorders in which anosmia and hypogonadotropic hypogonadism co-occur. KS is genetically heterogeneous, and there are at least eight genes involved in its pathogenesis, whereas CHARGE syndrome is caused by autosomal dominant mutations in only one gene, the CHD7 gene. Two independent studies showed that CHD7 mutations can also be found in a minority of KS patients. OBJECTIVE: We aimed to investigate whether CHD7 mutations can give rise to isolated KS or whether additional features of CHARGE syndrome always occur. DESIGN: We performed CHD7 analysis in a cohort of 36 clinically well-characterized Dutch patients with KS but without mutations in KAL1 and with known status for the KS genes with incomplete penetrance, FGFR1, PROK2, PROKR2, and FGF8. RESULTS: We identified three heterozygous CHD7 mutations. The CHD7-positive patients were carefully reexamined and were all found to have additional features of CHARGE syndrome. CONCLUSION: The yield of CHD7 analysis in patients with isolated KS seems very low but increases when additional CHARGE features are present. Therefore, we recommend performing CHD7 analysis in KS patients who have at least two additional CHARGE features or semicircular canal anomalies. Identifying a CHD7 mutation has important clinical implications for the surveillance and genetic counseling of patients
American Society for Clinical Oncology 40th Annual Meeting, New Orleans, LA, 5–8 June 2004: breast cancer highlights
Synthesis and Characterization of Core-shell ZrO2/PAAEM/PS Nanoparticles
This work demonstrates the synthesis of core-shell ZrO2/PAAEM/PS nanoparticles through a combination of sol–gel method and emulsifier-free emulsion polymerizaiton. By this method, the modified nanometer ZrO2cores were prepared by chemical modification at a molecular level of zirconium propoxide with monomer of acetoacetoxyethylmethacrylate (AAEM), and then copolymerized with vinyl monomer to form uniform-size hybrid nanoparticles with diameter of around 250 nm. The morphology, composition, and thermal stability of the core-shell particles were characterized by various techniques including transmission electron microscopy (TEM), X-ray diffractometer (XRD), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), and thermal-gravimetry analyzer (TGA). The results indicate that the inorganic–organic nanocomposites exhibit good thermal stability with the maximum decomposition temperature of ~447 °C. This approach would be useful for the synthesis of other inorganic–organic nanocomposites with desired functionalities
Coverage of endangered species in environmental risk assessments at EFSA
The EFSA performs environmental risk assessment (ERA) for single potential stressors such as plantprotection products, genetically modified organisms and feed additives, and for invasive alien speciesthat are harmful to plant health. This ERA focusses primarily on the use or spread of such potentialstressors in an agricultural context, but also considers the impact on the wider environment. It isimportant to realise that the above potential stressors in most cases contribute a minor proportion ofthe total integrated pressure that ecosystems experience. The World Wildlife Fund listed the relativeattribution of threats contributing to the declines in animal populations as follows: 37% fromexploitation (fishing, hunting, etc.), 31% habitat degradation and change, 13% from habitat loss, 7%from climate change, and only 5% from invasive species, 4% from pollution and 2% from disease. Inthis scientific opinion, the Scientific Committee gathered scientific knowledge on the extent of coverageof endangered species in current ERA schemes that fall under the remit of EFSA. The legal basis andthe relevant ecological and biological features used to classify a species as endangered areinvestigated. The characteristics that determine vulnerability of endangered species are reviewed.Whether endangered species are more at risk from exposure to potential stressors than other non-target species is discussed, but specific protection goals for endangered species are not given. Due toa lack of effect and exposure data for the vast majority of endangered species, the reliability of usingdata from other species is a key issue for their ERA. This issue and other uncertainties are discussedwhen reviewing the coverage of endangered species in current ERA schemes. Potential tools, such aspopulation and landscape modelling and trait-based approaches, for extending the coverage ofendangered species in current ERA schemes, are explored and reported
Phase II study of capecitabine in combination with paclitaxel in patients with anthracycline-pretreated advanced/metastatic breast cancer
Anticancer Gene Transfer for Cancer Gene Therapy
Gene therapy vectors are among the treatments currently used to treat malignant tumors. Gene therapy vectors use a specific therapeutic transgene that causes death in cancer cells. In early attempts at gene therapy, therapeutic transgenes were driven by non-specific vectors which induced toxicity to normal cells in addition to the cancer cells. Recently, novel cancer specific viral vectors have been developed that target cancer cells leaving normal cells unharmed. Here we review such cancer specific gene therapy systems currently used in the treatment of cancer and discuss the major challenges and future directions in this field
A dose escalation and pharmacokinetic study of biweekly pegylated liposomal doxorubicin, paclitaxel and gemcitabine in patients with advanced solid tumours
To determine the maximum tolerated doses (MTDs) and dose-limiting toxicities (DLTs) of pegylated liposomal doxorubicin (PLD), paclitaxel (PCX) and gemcitabine (GEM) combination administered biweekly in patients with advanced solid tumours. Twenty-two patients with advanced-stage solid tumours were treated with escalated doses of PLD on day 1 and PCX plus GEM on day 2 (starting doses: 10, 100 and 800 mg m−2, respectively) every 2 weeks. DLTs and pharmacokinetic (PK) parameters of all drugs were determined during the first cycle of treatment. All but six (73%) patients had previously received at least one chemotherapy regimen. The DLT dose level was reached at PLD 12 mg m−2, PCX 110 mg m−2 and GEM 1000 mg m−2 with neutropaenia being the dose-limiting event. Of the 86 chemotherapy cycles delivered, grade 3 and 4 neutropaenia occurred in 20% with no cases of febrile neutropaenia. Non-haematological toxicities were mild. The recommended MTDs are PLD 12 mg m−2, PCX 100 mg m−2 and GEM 1000 mg m−2 administered every 2 weeks. The PK data revealed no obvious drug interactions. Biweekly administration of PLD, PCX and GEM is a well-tolerated chemotherapy regimen, which merits further evaluation in various types of solid tumours
Measurement of the cosmic ray spectrum above eV using inclined events detected with the Pierre Auger Observatory
A measurement of the cosmic-ray spectrum for energies exceeding
eV is presented, which is based on the analysis of showers
with zenith angles greater than detected with the Pierre Auger
Observatory between 1 January 2004 and 31 December 2013. The measured spectrum
confirms a flux suppression at the highest energies. Above
eV, the "ankle", the flux can be described by a power law with
index followed by
a smooth suppression region. For the energy () at which the
spectral flux has fallen to one-half of its extrapolated value in the absence
of suppression, we find
eV.Comment: Replaced with published version. Added journal reference and DO
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