Tumor interactions with soluble factors and the nervous system

In the genomic era of cancer research, the development of metastases has been attributed to mutations in the tumor that enable the cells to migrate. However, gene analyses revealed that primary tumors and metastases were in some cases genetically identical and the question was raised whether metastasis formation might be an inherent feature of certain tumor cells. In contradiction to this view, the last decade of cancer research has brought to light, that tumor cell migration, similar to leukocyte and fibroblast migration, is a highly regulated process. The nervous system plays an important role in this regulation, at least in two respects: firstly, neurotransmitters are known to regulate the migratory activity of tumor cells, and secondly, nerve fibers are used as routes for perineural invasion. We also summarize here the current knowledge on the innervation of tumors. Such a process might establish a neuro-neoplastic synapse, with the close interaction of tumor cells and nerve cells supporting metastasis formation

Evaluation of the antitumour activity of coumarin in prostate cancer models

Responses to coumarin have been reported for patients suffering from malignant melanoma, metastatic renal carcinoma and, recently, advanced prostate cancer. These data together with some experimental evidence for antiprostatic effect prompted us to study the activity of coumarin in various prostate tumour models and evaluate the endocrine properties of this drug. In rats no antiandrogenic activity was found. The growth of Noble Nb-R prostate tumours of the rat was strongly inhibited by coumarin (40 mg/kg; administered three times per week), whereas the hormonally more sensitive Dunning R3327-G rat prostate carcinoma did not respond to coumarin (40 mg) even when the drug was administered daily. Coumarin was also shown to possess antimetastatic activity in a Dunning R3327-MatLu tumour model. In this model small pieces of the hormone-independent tumour were implanted into the ear of the animal and later resected to mimic the clinical situation where primary tumours have been removed. The number of lung metastases was reduced significantly by 40%-50% following the administration of coumarin (40 mg daily)

Sources of bias and uncertainty in a visual temporal individuation task

Despite a clear ability to detect temporal modulations of visual stimuli in excess of 50 Hz, temporal individuation and serial order judgment tasks can be performed only when stimuli alternate at much slower rates, and the nature of such sluggishness remains unclear. One example of a task with a slow temporal limit is the individuation of a cued letter in a rapid serial visual presentation (RSVP) stream. The present study investigates the nature of the code used to perform such a slow temporal individuation task and the sources of uncertainty involved. The results demonstrate that temporal, rather than ordinal, position in the RSVP stream is critical in serial order estimation, suggesting the involvement of a noisy temporal code. In addition to variability in temporal coding, observers’ choices are also limited by a number of other factors, such as categorical errors and biases related to the position of the cue in the letters’ stream. Attentional filtering improves categorization, but crucially, it does not seem to increase the temporal precision of judgment. Generalizing the present results, I suggest that perception of order is limited by an internal temporal sampling instability that is distinct and independent from attention and that, similarly to temporal jitter in a clock, acts as a low-pass filter that hinders the judgment of the order of events that unfold too quickly