Uracil-tegafur in gastric carcinoma: a comprehensive review.

1998 ◽  
Vol 16 (8) ◽  
pp. 2877-2885 ◽  
Author(s):  
H Takiuchi ◽  
J A Ajani
Keyword(s):  
North America ◽  
Gastric Carcinoma ◽  
Phase I ◽  
First Generation ◽  
Second Generation ◽  
Dihydropyrimidine Dehydrogenase ◽  
Pharmacokinetic Studies ◽  
Human Pharmacokinetics ◽  
Blood Concentrations ◽  
Tumor Tissues

PURPOSE The second-generation oral anticancer agent UFT, a combination of uracil and tegafur (TGF), results in a higher fluorouracil (5-FU) concentration in the tumor tissues than is achieved by TGF or comparable doses of intravenous 5-fluorouracil. UFT has been extensively studied in Japan and has been in use in the Orient for many years, particularly for patients with gastric carcinoma. UFT has recently entered extensive investigations in North America and Europe. METHODS Relevant studies that have chronicled the establishment of UFT, its mechanism of action, preclinical toxicology, human pharmacokinetics, phase I studies, and activity against gastric carcinoma are described in detail. RESULTS The uracil in UFT slows degradation of 5-FU by dihydropyrimidine dehydrogenase (DPD), which results in sustained concentrations of 5-FU in blood and tumor tissues. UFT is well tolerated, but such toxic effects as nausea, vomiting, and diarrhea are dose- and schedule-dependent. In phase I pharmacokinetic studies, UFT given orally on a 28-day schedule resulted in blood concentrations comparable to those following low-dose continuous intravenous infusion of 5-FU. In patients with gastric carcinoma, UFT alone has a response rate of approximately 20%. In the adjuvant setting, UFT plus mitomycin appears superior to TGF plus mitomycin. In Japan, UFT is part of the standard adjuvant chemotherapy for gastric carcinoma. CONCLUSION UFT is one of the first second-generation oral 5-FU prodrugs under investigation in North America and Europe. The literature suggests UFT is well tolerated and has cellular pharmacokinetic superiority over the first-generation 5-FU prodrug TGF. UFT has a more favorable toxicity profile than intravenous 5-FU. The issues of efficacy, patient convenience, and quality of life need to be studied in controlled randomized trials.

SUMMER DIAPAUSE IN PHYLLONORYCTER BLANCARDELLA (FABR.) (LEPIDOPTERA: GRACILLARIIDAE) IN ONTARIO

1986 ◽  
Vol 118 (1) ◽  
pp. 17-28 ◽  
Author(s):  
J.E. Laing ◽  
J.M. Heraty ◽  
J.E. Corrigan
Keyword(s):  
North America ◽  
First Generation ◽  
Second Generation ◽  
Eastern North America ◽  
Flight Period ◽  
Life Stages ◽  
Leaf Miners ◽  
Summer Generation ◽  
Summer Diapause ◽  
Phyllonorycter Blancardella

AbstractThe life stages of Phyllonorycter blancardella (Fabr.) were monitored in an orchard at Guelph, Ontario in 1981 and 1982 and the results showed discrepancies with the previous concept of a trivoltine species occurring throughout its range in eastern North America. Sleeve cages were used to monitor the development of the second, mid-summer generation of leaf miners in a low-maintenance orchard at Guelph in 1982 and 1984 and 2 commercial orchards at Simcoe, Ontario in 1984. The flight period of the first-generation adults occurred over approximately a 6-week period. From eggs laid early in the flight period, a large proportion of the larvae developed quickly and emerged to give a second-generation adult flight. As the flight period continued, there was an increase in the number of progeny whose development was delayed in the early instars. These larvae did not pupate until late fall and overwintered as pupae. Of the second-generation larvae, about 70–90% at Guelph and 35% at Simcoe had a delayed development (summer diapause) and formed a large proportion of the overwintering population.

The Biology of the Mountain-ash Sawfly, Pristiphora geniculata (Htg.) (Hymenoptera: Tenthredinidae), in Eastern Canada

1964 ◽  
Vol 96 (8) ◽  
pp. 1117-1133 ◽  
Author(s):  
R. S. Forbes ◽  
L. Daviault
Keyword(s):  
North America ◽  
Food Supply ◽  
First Generation ◽  
Second Generation ◽  
Limiting Factor ◽  
Eastern Canada ◽  
Density Dependent ◽  
Control Factors ◽  
Mountain Ash ◽  
Two Generations

AbstractThe mountain-ash sawfly, Pristiphora geniculata (Htg.), a pest on Sorbus spp., is known to occur in Europe, Asia, and North America. It has two generations a year in eastern Canada but only one in northern Quebec. The first generation predominates. The sawfly overwinters as a larva in a cocoon in litter or soil. Adults emerge from late May to early July, and lay eggs in pockets between the epidermal lavers around the edges of leaflets. The eggs hatch in about a week and the larvae feed from two to three weeks. The second generation, which starts in late July, is usually small. Adults producing the first generation may come from both generations of the preceding year whereas adults producing the second generation stem only from the first. Parthenogenesis is facultative and arrhenotokous; about 61% of adults reared were females. The male larvae have four instars and the female five. Some larvae remain in diapause up to five years. Foliage consumption of female larvae was about 1.4 times that of male larvae.P. geniculata lacks adequate density-dependent control factors and an important limiting factor may be its scattered food supply. The introduction of parasites, predators, or disease organisms might be beneficial.

Do remittances differ depending on migration pathway and length of stay?

2016 ◽  
Vol 1 (1) ◽  
pp. 105-118
Author(s):  
Anita Pugliese ◽  
Julie Ray ◽  
Neli Esipova
Keyword(s):  
Length Of Stay ◽  
First Generation ◽  
Second Generation ◽  
Global Analysis ◽  
Large Sample ◽  
Migration Pathway ◽  
First Generation Migrants ◽  
Second Generation Migrants

This paper reports the results from Gallup’s global analysis of the likelihood of first-generation migrants, second-generation migrants and the native-born to send financial help in the form of money or goods to others inside or outside their respective country of residence. The findings in this paper are based on more than 450,000 interviews conducted through Gallup’s World Poll in 157 countries in 2012, 2013 and 2014. The sample includes more than 26,000 first-generation migrants and more than 20,000 second-generation migrants. The large sample enables Gallup to analyze first-generation migrants by the duration of their stay in their adopted country and compare their remittance behaviors with second-generation migrants and the native-born.

Marcuse and Habermas's Political Ideas in English

2019 ◽  
pp. 215
Author(s):  
Asaad Abdullwahab AbdulKarim ◽  
Waleed Massaher Hamad ◽  
Salah Ibrahim Hamadi
Keyword(s):  
First Generation ◽  
Second Generation ◽  
Frankfurt School ◽  
Western Thought ◽  
Political Ideas ◽  
Important Impact

Abstract     The Frankfurt School is characterized by its critical nature and it is the result of the Marxist socialist thought as it contributed to the development of the German thought in particular and the Western thought in general through important ideas put forward by a number of pioneers in the various generations of the school and most notably through the leading pioneer in the first generation, Marcuse, and the leading pioneer of the second  generation, Habermas, whose political ideas had an important impact on global thinking and later became the basis of the attic of many critical ideas. In spite of the belief of the school members in the idea of the criticism of power and community, each had his own ideas that distinguish him from the others.

Pharmakotherapie update

2020 ◽  
Vol 25 (1) ◽  
pp. 23-32
Author(s):  
Gerd Laux
Keyword(s):  
First Generation ◽  
Second Generation ◽  
Therapeutische Maßnahmen ◽  
Second Generation Antipsychotics

Für die Therapie schizophrener Erkrankungen sind seit fast 60 Jahren Antipsychotika/Neuroleptika aufgrund ihrer antipsychotischen Wirkung von zentraler Bedeutung. Die Einteilung kann unter verschiedenen Gesichtspunkten erfolgen (chemische Struktur, neuroleptische Potenz, Rezeptorprofil), heute werden üblicherweise unterschieden typische (traditionelle, klassische, konventionelle) Antipsychotika der ersten Generation ‒ »First Generation Antipsychotics« (FGA) ‒ und sog. atypische (»neuere«) Neuroleptika bzw. Antipsychotika der zweiten Generation ‒»Second Generation Antipsychotics« (SGA). Hierzu zählen Aripiprazol, Asenapin, Cariprazin, Clozapin, Olanzapin, Quetiapin, Risperidon, Sertindol und Ziprasidon. Hierbei handelt es sich um keine homogene Gruppe – sowohl neuropharmakologisch (Wirkmechanismus), als auch hinsichtlich klinischem Wirkprofil und dem Nebenwirkungsspektrum bestehen z. T. erhebliche Unterschiede. Neben der Akut-Medikation ist eine Langzeitmedikation bzw. Rezidivprophylaxe mit Antipsychotika für die Rehabilitation vieler schizophrener Patienten im Sinne eines »Stresspuffers« von grundlegender Bedeutung. In Placebo-kontrollierten Studien trat bei Patienten, die über ein Jahr behandelt wurden, bei etwa 30% unter Neuroleptika ein Rezidiv auf, unter Placebo bei mehr als 70%. Für die Langzeitbehandlung bietet sich der Einsatz von Depot-Neuroleptika an, neu entwickelt wurden Langzeit-Depot-Injektionen mit Intervallen von bis zu 3 Monaten. Grundsätzlich ist die niedrigstmögliche (wirksame) Dosis zu verwenden. Im Zentrum der Nebenwirkungen (UAW) standen lange Zeit extrapyramidal-motorische Bewegungsstörungen (EPMS), mit der Einführung von Clozapin und anderen atypischen Antipsychotika der zweiten Generation gewannen andere Nebenwirkungen an Bedeutung. Hierzu zählen Gewichtszunahme, Störungen metabolischer Parameter und ein erhöhtes Risiko für Mortalität und zerebrovaskuläre Ereignisse bei älteren Patienten mit Demenz. Entsprechende Kontrolluntersuchungen sind erforderlich, für Clozapin gibt es aufgrund seines Agranulozytose-Risikos Sonderbestimmungen. Immer sollte ein Gesamtbehandlungsplan orientiert an der neuen S3-Praxisleitlinie Schizophrenie der DGPPN aufgestellt werden, der psychologische und milieu-/sozial-therapeutische Maßnahmen einschließt. Standard ist heute auch eine sog. Psychoedukation, für Psychopharmaka liegen bewährte Patienten-Ratgeber vor.

The Inheritors’ Coming of Age

2018 ◽  
Author(s):  
Elisabeth Schimpfössl
Keyword(s):  
First Generation ◽  
Second Generation ◽  
Coming Of Age ◽  
Next Generation ◽  
Privileged Status ◽  
The Rich

Chapter 7 focuses on the upbringing of the second generation of the Russian bourgeoisie. As the first generation of wealthy Russians grows older, they are becoming more aware of their own mortality and are preparing to hand over their wealth to the next generation. It seems that rich Russians are yet to find a convincing narrative to justify their children’s legitimate entitlement to wealth that does not contradict their own everyday ideology of being self-made. Nevertheless, a two-pronged approach is emerging. First, in line with the shift toward new modesty, children are being encouraged to cultivate a habitus of privilege, as Sherman suggests in the case with wealthy US Americans, which makes them appear morally worthy in an environment marked by extreme inequality. Second, via their philanthropy the rich are supporting institutions and scholars in an effort to strengthen a dynamic capitalist environment in which privileged status is respected.

scholarly journals EPCT-19. A PHASE I STUDY OF RIBOCICLIB AND EVEROLIMUS FOLLOWING RADIATION THERAPY IN CHILDREN WITH NEWLY DIAGNOSED NON-BIOPSIED DIFFUSE PONTINE GLIOMAS (DIPG) AND RB+ BIOPSIED DIPG AND HIGH GRADE GLIOMAS (HGG)

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii307-iii307
Author(s):  
Mariko DeWire ◽  
James Leach ◽  
Christine Fuller ◽  
Peter de Blank ◽  
Trent Hummel ◽  
...  
Keyword(s):  
Phase I ◽  
Phase I Study ◽  
Single Agent ◽  
Maximum Tolerated Dose ◽  
Pharmacokinetic Studies ◽  
High Grade ◽  
Newly Diagnosed ◽  
High Grade Gliomas ◽  
Grade 3 ◽  
Expansion Cohort

Abstract Genomic aberrations in the cell cycle and mTOR pathways have been reported in diffuse pontine gliomas (DIPG) and high-grade gliomas (HGG). Dual inhibition of CDK4/6 (ribociclib) and mTOR (everolimus) has strong biologic rationale, non-overlapping single-agent toxicities, and adult clinical experience. The maximum tolerated dose (MTD) and/or recommended phase two dose (RP2D) of ribociclib and everolimus administered during maintenance therapy following radiotherapy was determined in the phase I study as a rolling 6 design. Ribociclib and everolimus were administered once daily for 21 days and 28 days, respectively starting two-four weeks post completion of radiotherapy. All HGG patients and any DIPG patient who had undergone biopsy were screened for RB protein by immunohistochemistry. Eighteen eligible patients enrolled (median age 8 years; range: 2–18). Six patients enrolled at dose levels 1,2, and 3 without dose limiting toxicities (DLT). Currently, five patients are enrolled at dose level 3 expansion cohort. The median number of cycles are 4.5 (range: 1–20+). Among the expansion cohort, one dose limiting toxicity included a grade 3 infection and one patient required a dose reduction in course 3 due to grade 3 ALT and grade 4 hypokalemia. The most common grade 3/4 adverse events included neutropenia. Preliminary pharmacokinetic studies on 12 patients suggest an impact of ribociclib on everolimus pharmacokinetics. The MTD/RP2D of ribociclib and everolimus following radiotherapy in newly diagnosed DIPG and HGG is anticipated to be 170 mg/m2/day x 21 days and 1.5 mg/ m2/day every 28 days which is equivalent to the adult RP2D.

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