Spatial cooperation

Spatial cooperation is a term coined to describe a situation when disease in one particular anatomic site is missed by one modality but is treated adequately by another. The essence of this is that radiation is a local therapy that will not impact on metastatic disease beyond the planned field borders. Systemic cytotoxic chemotherapy is traditionally used to address the potential distant spread of cancer. In the original description of this mechanism there is no assumption of an interaction between the drugs and radiation with the idea being that the best radiation and best chemotherapy be administered independently of toxicities. The classic example used in several textbooks to illustrate this is the treatment of childhood leukemia with systemic chemotherapy, while their central nervous system, a potential sanctuary site where disease is not treated adequately by chemotherapy, is treated by radiation (28). The reality of the interaction between radiation and chemotherapy is that the dose and timing of radiation are adjusted accordingly to minimize their impact on the neural tissues. 

Spatial cooperation Radiation is more effective at controlling the primary bulky disease but is unable to affect distant micrometastases. Chemotherapy, on the other hand, can deal with micrometastases but is unable to affect the large primary tumor. The combination of both local (radiation) and systemic (chemotherapy) approaches then maximizes therapeutic impact. 

Considering the spatial cooperation between the ultimate unit and the approaching monomer molecule through complexation with the metal atom, the growing chain end control mechanism has been postulated to be valid for the coordination polymerisation of alanine iV-carboxyanhydride in the presence of metal alkyls [75]. 

The kinetic cooperativity can be distinguished from the substrate binding cooperativity (spatial cooperativity by means of homotropic interactions) by means of binding studies, measurements of the initial speed and the determination of the type of conformation (9,12). 

Fig. 10.1. Differences in quantitative cell kill and time course. Influence of different therapeutic modalities on number of tumor cells during a course of treatment, based on models (Tannock 1989, 1992 Minchinton and Tannock 2006). The dashed line represents the border between microscopic and macroscopic tumors, defined as a size of approximately 5 mm. Compared with surgical resection and fractionated radiotherapy, multiple courses of chemotherapy (in this case six, indicated by arrows) are less efficient in cell kill. While microscopic disease might be eradicated (lower chemotherapy curve), clinical evidence su ests that most macroscopic solid tumors (exception more sensitive testicular cancers) will shrink temporarily but eventually regrow from surviving residues (upper chemotherapy curve). As shown in the inset, the strength of chemotherapy in combination with radiation treatment (in addition to spatial cooperation) is the modification of the slope of the curve...

NFAT2 plays a key role in the development of the embryo s heart. In the precursor cells, there is a temporal and spatial specific expression of NFAT2, which directs the formation of the valves and the septum in the heart. In the adult heart, NFAT proteins also cooperate with transcription factors of the GATA and MEF2 families to regulate cardiac muscle hypertrophic responses. 

In the case of amphiphilic molecules, characterized by the coexistence of spatially separated apolar (alkyl chains) and polar moieties, both parts cooperate to drive the intermolecular aggregation. This simple but pivotal peculiarity makes amphiphilic molecules soluble in both polar and apolar solvents and able to realize, in suitable conditions, an impressive variety of molecular aggregates characterized by spatially separated apolar and polar domains, local order at short times and fluidity at long times, and differences in size, shape (linear or branched chains, cyclic or globular aggregates, extended fractal-like molecular networks), and lifetime. 

Cooper, D. L., Smith, G. E., Regan, M., Large, S., and Groenewegen, P. P. (2008). Tracking the spatial diffusion of influenza and norovirus using telehealth data A spatiotemporal analysis of syndromic data. BMC Med. 6,16. 

The formation of ER dimers can be favored once the first monomer has bound to the DNA, since this presents positive cooperation in binding the next monomer. In any case, DNA binding creates a greater compaction of the dimer that results in a subsequent spatial restructuring of the receptor molecules. 

The concept of rotational catalysis by ATP synthase is based on (a) P and 0 exchange rate data attesting to strong cooperativity with sequential participation of several catalytic sites (b) Pi and ATP 0-isotopomer distributions indicating that all catalytic sites exhibit identical catalysis and (c) that catalysis is strongly influenced by the y-subunit whose primary structure was not likely to account for spatially similar interactions with the /3-subunits . The model was found to be compatible with the 2.8 A resolution structure of bovine heart mitochondrial Fi-ATPase. ... 

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