Isolated limb perfusion with actinomycin D and TNF-alpha results in improved tumour response in soft-tissue sarcoma-bearing rats but is accompanied by severe local toxicity

Previously we demonstrated that addition of Tumour Necrosis Factor-α to melphalan or doxorubicin in a so-called isolated limb perfusion results in synergistic antitumour responses of sarcomas in both animal models and patients. Yet, 20 to 30% of the treated tumours do not respond. Therefore agents that synergise with tumour necrosis factor alpha must be investigated. Actinomycin D is used in combination with melphalan in isolated limb perfusion in the treatment of patients with melanoma in-transit metastases and is well known to augment tumour cell sensitivity towards tumour necrosis factor alpha in vitro. Both agents are very toxic, which limits their systemic use. Their applicability may therefore be tested in the isolated limb perfusion setting, by which the tumours can be exposed to high concentrations in the absence of systemic exposure. To study the beneficial effect of the combination in vivo, BN-175 soft tissue sarcoma-bearing rats were perfused with various concentrations of actinomycin D and tumour necrosis factor alpha. When used alone the drugs had only little effect on the tumour. Only when actinomycin D and tumour necrosis factor alpha were combined a tumour response was achieved. However, these responses were accompanied by severe, dose limiting, local toxicity such as destruction of the muscle tissue and massive oedema. Our results show that isolated limb perfusion with actinomycin D in combination with tumour necrosis factor alpha leads to a synergistic anti-tumour response but also to idiosyncratic locoregional toxicity to the normal tissues. Actinomycin D, in combination with tumour necrosis factor alpha, should not be explored in the clinical setting because of this. The standard approach in the clinic remains isolated limb perfusion with tumour necrosis factor alpha in combination with melphalan

Risk, price and pay-off: A study explaining wagering and gambling behaviour using prevalent lottery models with an application of two stage least square regression

The study explains behavior in an uncertainty environment. As gambling is perceived by many to be an act violating the basic principles of individual rationality, the determining factors that contribute to a gambler\u27s decision to wager a bet, and at the same time the reasons for such, contribute to the interest in the said field of study. The study adopts the most popular lottery model--the Effective Price Model, as well a proposed alternative to such--the Jackpot Prize Model, applied in the United Kingdom as its working model. The integrities and applicability of the said models are tested in the Philippine setting in the duration of this study. Furthermore, this study applies a two-stage regression process using lotto 6/45 data taken from the Philippine Charity Sweepstakes Office (PCSO) to run the two models