In vitro characterization of cells derived from chordoma cell line U-CH1 following treatment with X-rays, heavy ions and chemotherapeutic drugs

<p>Abstract</p> <p>Background</p> <p>Chordoma, a rare cancer, is usually treated with surgery and/or radiation. However, very limited characterizations of chordoma cells are available due to a minimal availability (only two lines validated by now) and the extremely long doubling time. In order to overcome this situation, we successfully derived a cell line with a shorter doubling time from the first validated chordoma line U-CH1 and obtained invaluable cell biological data.</p> <p>Method</p> <p>After isolating a subpopulation of U-CH1 cells with a short doubling time (U-CH1-N), cell growth, cell cycle distribution, DNA content, chromosome number, p53 status, and cell survival were examined after exposure to X-rays, heavy ions, camptothecin, mitomycin C, cisplatin and bleocin. These data were compared with those of HeLa (cervical cancer) and U87-MG (glioblastoma) cells.</p> <p>Results</p> <p>The cell doubling times for HeLa, U87-MG and U-CH1-N were approximately 18 h, 24 h and 3 days respectively. Heavy ion irradiation resulted in more efficient cell killing than x-rays in all three cell lines. Relative biological effectiveness (RBE) at 10% survival for U-CH1-N was about 2.45 for 70 keV/μm carbon and 3.86 for 200 keV/μm iron ions. Of the four chemicals, bleocin showed the most marked cytotoxic effect on U-CH1-N.</p> <p>Conclusion</p> <p>Our data provide the first comprehensive cellular characterization using cells of chordoma origin and furnish the biological basis for successful clinical results of chordoma treatment by heavy ions.</p

Wie nicht-lineare Zeitrepräsentationen zukunftsbezogene Urteile und Entscheidungen beeinflussen können : ein entwicklungspsychologischer Ansatz

Die vorliegende Arbeit untersuchte in drei Experimenten den Einfluss der Zeit auf Bewertungen und Entscheidungen in unterschiedlichen Altersstufen. Experiment 1 beschäftigte sich mit dem Einfluss des Zeithorizontes auf die Beurteilung der Riskantheit einer Investition sowie auf das Investitionsverhalten bei 12-Jährigen. Im Gegensatz zu typischen Ergebnissen von Erwachsenen führte bei den Kindern eine lange Zeitspanne zwischen Investition und Erfolgsfeedback zur Annahme eines höheren Risikos und damit zu geringeren Investitionen. In Experiment 2 wurde die Bewertung materieller und nicht-materieller Werte, deren Erhalt verzögert war, bei 12-Jährigen und Erwachsenen untersucht. Dabei zeigte sich, dass Erwachsene Geld als materiellen Wert und Hilfe als nicht-materiellen Wert in ähnlicher Weise mit zunehmender Verzögerung abwerteten. Die Kinder hingegen werteten das verzögerte Geld deutlich stärker ab als Erwachsene, die Hilfe jedoch gar nicht. In Experiment 3 wurde die Entwicklung des Wissens über exponentielles Mengenwachstum in verschiedenen Altersgruppen untersucht. So schätzten 13-Jährige ein solches Wachstum normativ, doch bereits 9-Jährige unterschieden in ihren Schätzungen bedeutsam zwischen exponentiellem und linearem Wachstum, was für ein frühes intuitives Wissen in diesem Bereich spricht. Im Anschluss wurde ein Modell zur altersabhängigen Zeitrepräsentation entwickelt, das versucht, den Einfluss der Zeitrepräsentation in allen drei Experimenten zu erklären. Three experiments were conducted to examine the role of time on judgments and decisions in different age groups. Experiment 1 investigated the influence of the time horizon on 12-year-olds judgments of riskiness and amount of investment into an endeavour. In contrast to typical results of adults, a long time span between the investment and a feedback about its success yielded judgments of higher riskiness and, thus, lower investments in children. Experiment 2 assessed 12-year-olds and adults evaluation of material and immaterial values, whose receipt was either immediate or delayed. Results showed similar subjective discount rates for delayed money (i.e. material value) and delayed help (i.e. immaterial value) in adults. However, children discounted the delayed money more than adults, but they devaluated the delayed help not at all. Experiment 3 investigated the development of knowledge about exponential growth in children, aged 7 to 13 years, and adults. Only 13-year-olds showed a normative estimation of exponential growth. However, 9-year-olds already differentiated between exponential and linear growth in their estimations. This result points to an early intuitive knowledge in this domain. Finally, a model of age-related time representation was proposed to explain the role of time representation in the three experiments

Five-year quality of life assessment after carbon ion radiotherapy for prostate cancer

The aim of this study was to prospectively assess 5-year health-related quality of life (HRQOL) of patients treated with carbon ion radiotherapy (C-ion RT) for clinically localized prostate cancer. A total of 417 patients received carbon ion radiotherapy at a total dose of 63–66 Gray-equivalents (GyE) in 20 fractions over 5 weeks, and neoadjuvant and adjuvant androgen deprivation therapy (ADT) were administered for intermediate and high-risk patients. A HRQOL assessment was performed at five time points (immediately before the initiation of C-ion RT, immediately after, and at 12, 36 and 60 months after completion of C-ion RT) using Functional Assessment of Cancer Therapy (FACT) questionnaires. FACT-G and FACT-P scores were significantly decreased; however, the absolute change after 60 months was minimal. The transient decreases in the Trial Outcome Index (TOI) score returned to their baseline levels. Use of ADT, presence of adverse events, and biochemical failure were related to lower scores. Scores of subdomains of FACT instruments indicated characteristic changes. The pattern of HRQOL change after C-ion RT was similar to that of other modalities. Further controlled studies focusing on a HRQOL in patients with prostate cancer are warranted

Significant impact of biochemical recurrence on overall mortality in patients with high-risk prostate cancer after carbon-ion radiotherapy combined with androgen deprivation therapy

BACKGROUNDWhether biochemical recurrence (BR) is a significant predictive factor of mortality after definitive radiation therapy for prostate cancer remains unknown. The aim of the current study was to investigate the relation between BR and overall mortality (OAM) in high-risk prostate cancer patients who were treated with carbon-ion radiotherapy (CIRT) and had long-term follow-up in 2 prospective trials.METHODSIn the 2 phase 2 clinical trials, which involved 466 prostate cancer patients who received 63.0 to 66.0 Gy of CIRT (relative biological effect) in 20 fractions between 2000 and 2007, 324 patients who were deemed to be at high risk on the basis of the modified D\u27Amico classification criteria and received CIRT along with androgen-deprivation therapy (ADT) were examined. The OAM rate was adjusted for the ADT duration, and multivariate analyses using a Cox proportional hazards model were performed for OAM with BR as a time-dependent covariate.RESULTSThe median follow-up period was 107.4 months, and the 5- and 10-year OAM rates after adjustments for the ADT duration were 7.0% (95% confidence interval [CI], 4.0%-9.4%) and 23.9% (95% CI, 16.4%-26.2%), respectively. A multivariate analysis revealed that the presence of BR (hazard ratio, 2.82; 95% Cl, 1.57-5.08; P = .001) was one of the predictive factors for OAM. On the other hand, the duration of ADT had no impact on OAM.CONCLUSIONSBR after CIRT combined with ADT is an independent predictive factor for OAM in high-risk prostate cancer patients. The results of this study could be applied to other high-dose radiation therapies

Field experiments in labor economics

In this thesis I show with three studies how field experiments can enhance our understanding of labor markets. Economists traditionally assume that individuals exclusively respond to monetary incentives. As a consequence, if workers have no prospect of future employment at the firm and pay is not contingent on their performance, a wage change should not affect effort. Some economists, however, have recognized that this narrow view of human motivation may severely limit our progress in understanding incentives. In Chapters 2 and 3, I investigate the role of psychological motives like the desire to reciprocate in the context of a real‐life work environment. The first experiment explores the impact of a wage increase on work performance when there is no economic reason for workers to change their effort. I find that workers reciprocate a generous wage with higher performance, particularly those workers who care about fairness and felt underpaid prior to the wage increase. The second experiment investigates the effects of a wage cut on performance when either all workers in a team or only some of them suffer the cut. I show that a general pay cut reduces performance, while a wage cut for only some of the workers reduces their performance more than twice as much. This finding demonstrates the powerful force of social comparison and the need to build the social nature of humans into economic theory. In Chapter 4, I examine the joint effects of monetary incentives and social interaction on work performance. Many jobs offer wage schemes that create positive or negative externalities on coworkers. Whether or not workers have the possibility to interact socially at work may distort the intended incentives of these schemes. I find that under relative incentives, when own effort imposes a negative externality on the coworker’s income, social interaction works against monetary incentives and leads to low performance due to collusion. However, the more workers differ in skills the less able they are to sustain collusive agreements. In der vorliegenden Dissertation zeige ich anhand von drei Studien wie Feldexperimente unser Verständnis von Arbeitsmärkten verbessern können. Ökonomen gehen traditionell davon aus, dass Individuen ausschliesslich auf materielle Anreize reagieren. Wenn also Arbeitskräfte keine Aussicht auf eine langfristige Anstellung haben und deren Lohn nicht von der Leistung abhängt, dann sollte eine Lohnveränderung keinen Einfluss auf die Arbeitsleistung haben. Manche Ökonomen haben jedoch erkannt, dass diese Sichtweise des menschlichen Verhaltens beschränkt ist und unseren Fortschritt im Verständnis von Anreizen bremsen kann. In den Kapiteln 2 und 3 untersuche ich die Bedeutung von psychologischen Motiven wie Fairness oder Reziprozität in echten Arbeitsumgebungen. Das erste Experiment untersucht den Einfluss einer Lohnerhöhung auf die Arbeitsleistung, wenn Arbeitskräfte keinen ökonomischen Grund haben, ihren Arbeitseinsatz zu ändern. Diese Studie zeigt, dass Arbeitskräfte einen grosszügigen Lohn mit höherer Arbeitsleistung erwidern. Dies gilt besonders für diejenigen, die Fairness als wichtig empfinden und sich vor der Lohnerhöhung unterbezahlt fühlten. Das zweite Experiment untersucht die Wirkung einer Lohnkürzung auf die Arbeitsleistung, wenn entweder das ganze Team oder nur einen Teil davon betroffen ist. Diese Studie zeigt auf, dass eine generelle Lohnkürzung die Arbeitsleistung senkt, wohingegen eine Lohnkürzung nur für einzelne Arbeitskräfte deren Leistung um mehr als das Doppelte reduziert. Diese Erkenntnis unterstreicht die Bedeutung von sozialen Motiven und die Notwendigkeit einer Veränderung des Menschenbilds in der Ökonomie. In Kapitel 4 erforsche ich den gemeinsamen Einfluss von materiellen Anreizen und sozialer Interaktion auf die Arbeitsleistung. Viele Firmen bieten Lohnsysteme an, bei welchen die eigene Leistung vor‐ oder nachteilhafte Nebeneffekte auf das Einkommen der Arbeitskollegen hat. Soziale Interaktion am Arbeitsplatz kann dabei die Anreize dieser Lohnsysteme verzerren. Diese Studie findet heraus, dass bei Entlohnung der Arbeitskräfte durch Turnieranreize, d.h. wenn die eigene Leistung sich nachteilhaft auf das Einkommen der Arbeitskollegen auswirkt, soziale Interaktion die Anreize ausser Kraft setzt und zu geheimen Absprachen führt. Wenn hingegen Arbeitskräfte sehr unterschiedliche Fähigkeiten besitzen, dann sind geheime Absprachen schwieriger aufrecht zu halten

Carbon ion radiotherapy for basal cell adenocarcinoma of the head and neck: preliminary report of six cases and review of the literature

<p>Abstract</p> <p>Background</p> <p>Basal cell adenocarcinoma accounts for approximately 1.6% of all salivary gland neoplasms. In this report, we describe our experiences of treatment for BCAC with carbon ion radiotherapy in our institution.</p> <p>Methods</p> <p>Case records of 6 patients with diagnosis of basal cell adenocarcinoma of the head and neck, who were treated by carbon ion radiotherapy with 64.0 GyE/16 fractions in our institution, were retrospectively reviewed.</p> <p>Results</p> <p>In a mean follow-up period of 32.1 months (14.0-51.3 months), overall survival and local control rates of 100% were achieved. Only one grade 4 (CTCAE v3.0) late complication occurred. There was no other grade 3 or higher toxicity.</p> <p>Conclusions</p> <p>Carbon ion radiotherapy should be considered as an appropriate curative approach for treatment of basal cell adenocarcinoma in certain cases, particularly in cases of unresectable disease and postoperative gross residual or recurrent disease.</p