Tumor structure

Motility and Invasion of Cells from 3-D Tumor Structures... 

Positron emission tomography (PET) is used in the diagnosis of cancer, but because it lacks anatomical detail, it is used in combination with CT scans. MRI scans provide superior contrast to GT for determining tumor structure and integrating PET and MRI into a single modality would be highly desirable and is in development... 

Fig. 13.5 Proteasome inhibitors used (or intended) for the treatment of relapsed multiple myeloma, mantle cell lymphoma, and some other tumors. Structures of the peptide boronates bortezomib and the orally active MLN9708, the peptide epoxyketone carfilzomib, and the y-lactam-p-lactone bicyclics sallnosporamide A (marizomib) and omuralide (P-clastolactacystin), both derived from natural sources. The drugs inhibit normal proteasome action by binding to the p-subunit proteolytic sites in the 20S core (see Fig. 13.4)...

Olfactory neuroblastoma or esthesioneuroblastoma is found at the frontobasis as a paramedian tumor structure that may extend from the nasal cavity into the orbit (Mueller-Forell and Pitz 2004). 

Mahgnant adenoid-cystic carcinoma of the lacrimal gland presents clinically with a hard and painful nodule of the lateral upper eyelid and demonstrates at cross-sectional imaging as a poorly delineating, nodular tumorous structure with erosion of adjacent bony structures (Mueller-Forell and Pitz 2004). 

Beginning in the 1980s research directed toward the isolation of new drugs derived from natural sources identified a family of tumor inhibitory antibiotic substances characterized by novel struc tures containing a C C—C=C—C C unit as part of a nine or ten membered ring With one double bond and two triple bonds (-ene + di- + -yne) these com pounds soon became known as enediyne antibiotics The simplest member of the class is dynemian A most of the other enediynes have even more compli cated structures... 

By examining some of the over one thousand tumor-causing point mutations of p53 in the light of its structure, we can identify features of p53 that are necessary for tumor suppression. The amino acids most frequently changed in cancer cells are at or near the protein-DNA interface residues that are infrequently mutated, if at all, are in general far from the DNA-binding site. 

Thirty percent of the tumor-derived mutations are in L3, which contains the single most frequently mutated residue, Arg 248. Clearly the interaction between DNA and the specific side chain of an arginine residue inside the minor groove is of crucial importance for the proper function of p53. It is an open question whether this interaction is needed for the recognition of specific DNA sequences, or is required for the proper distortion of the DNA structure, or a combination of both. Other residues that are frequently mutated in this region participate in interactions with loop L2 and stabilize the structures of loops L2 and L3. Mutations of these residues presumably destabilize the structure so that efficient DNA binding can no longer take place. 

Cho, Y., et al. Crystal structure of a p53 tumor suppres-sor DNA complex understanding tumorigenic mutations. Science 265 346-355, 1994. 

Jeffrey, P.D., Gorina, S., Pavletich, N.P. Crystal structure of the tetramerization domain of the p53 tumor suppressor at 1.7 Angstroms. Science 267 1498-1502, 1995. 

In summary, structural studies of Ras and Gq with GTP-yS and a transition state analog have illuminated the catalytic mechanism of their GTPase activity, as well as the mechanism by which GTP hydrolysis is stimulated by GAP and RGS. In addition, these structural studies have shown how tumor-causing mutations affect the function of Ras and Gq. 

The process of identifying chemical healtli liazards should also incorporate the near term (release into tlie environment) and long term fate of the chemical health hazard following entry into the human body. Non-carcinogcnic effects include all toxicological responses except tumors. Not all tumors are cancerous. Malignant tumors are cancerous and spread, or metastasize, to surrounding structures. 

Oligosaccharides also occur widely as components (via glycosidic bonds) of antibiotics derived from various sources. Figure 7.20 shows the structures of a few representative carbohydrate-containing antibiotics. Some of these antibiotics also show antitumor activity. One of the most important of this type is bleomycin A2, which is used clinically against certain tumors. 

Farnesyl transferase from rat cells is a heterodimer consisting of a 48 kD u-snbnnit and a 46 kD /3-snbnnit. In the structure shown here, helices 2 to 15 of the u-snbnnit are folded into seven short coiled coils that together form a crescent-shaped envelope partially surrounding the /3-snbnnit. Twelve helices of the /3-snl> nnit form a novel barrel motif that creates the active site of the enzyme. Farnesyl transferase inhibitors, one of which is shown here, are potent suppressors of tumor growth in mice, but their value in humans has not been established. 

The structure of 1-739,749, a farnesyl transferase inhibitor that is a potent tumor growth suppressor. 

Structural basis of protein kinase C activation by heterocyclic tumor promoters 98ACR163. 

The reduced symmetry of the chromophore, which still contains 187t-electrons and is therefore an aromatic system, influences the electronic spectrum which shows a bathochromic shift and a higher molar extinction coefficient of the long-wavelength absorption bands compared to the porphyrin, so that the photophysical properties of the chlorins resulting from this structural alteration render them naturally suitable as pigments for photosynthesis and also make them of interest in medical applications, e.g. photodynamic tumor therapy (PDT).2... 

The photophysical properties of porphycenes make these structures potential sensitizers for an application in Photodynamic Tumor Therapy (PDT). To improve the photophysical properties and to modify possible biological activity it is necessary to have porphycenes with an extended chromophore and/or with additional functional groups for further modifications. The Diels-Alder reaction of a vinyl porphycene allows for the preparation of benzoporphycenes with an extended chromophore9 and additional functional groups (cf. Section 1.1.2.4.). 

The breast cancer resistance protein (BCRP) belongs to the G-branch of the ABC-transporter family (ABCG2). In contrast to most other ABC-proteins, BCRP consists of only one transmembrane domain (TDM) with one nucleotide binding fold (NBF) at its C-terminus. Because of this structural characteristic BCRP as well as other ABC-transporters with only one TMD are termed half transporters. To achieve functional activity these transporters have to form hetero- or homodimers. BCRP is involved in the multidrug resistance of certain tumors and transports endogenous compounds like cholesterol and steroid hormones. 

Treatment for tumor patients with synthetic drags -chemotherapeutics - that may be of completely different chemical structure. The main goal of tumor chemotherapy is to achieve a selective toxicity for the tumor without causing damage to the host, for instance by combining several cytostatic drags at doses lower than required for monotherapy. 

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