Recent epidemiologic, genetic, and molecular studies suggest infection and inflammation initiate certain cancers, including those of the prostate. The American Cancer Society, estimates that approximately 20% of all worldwide cancers are caused by infection. Mycoplasma, a genus of bacteria that lack a cell wall, are among the few prokaryotes that can grow in close relationship with mammalian cells, often without any apparent pathology, for extended periods of time. In this study, the capacity of Mycoplasma genitalium, a prevalent sexually transmitted infection, and Mycoplasma hyorhinis, a mycoplasma found at unusually high frequency among patients with AIDS, to induce a malignant phenotype in benign human prostate cells (BPH-1) was evaluated using a series of in vitro and in vivo assays. After 19 weeks of culture, infected BPH-1 cells achieved anchorage-independent growth and increased migration and invasion. Malignant transformation of infected BPH-1 cells was confirmed by the formation of xenograft tumors in athymic mice. Associated with these changes was an increase in karyotypic entropy, evident by the accumulation of chromosomal aberrations and polysomy. This is the first report describing the capacity of M. genitalium or M. hyorhinis infection to lead to the malignant transformation of benign human epithelial cells and may serve as a model to further study the relationship between prostatitis and prostatic carcinogenesis.
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Fiber connections of the corpus glomerulosum (CG) in a teleost, Navodon modestus, were studied by means of horseradish peroxidase (HRP) and the Fink-Heimer methods. The CG is divided into a pars anterior (GA) and a pars rotunda (GR). Both the GR and the GA have the same cell components and glomeruli. The GR is composed of four layers arranged concentrically around a central fiber net in the following order (Ito and Kishida, '75): a glomerular layer, a fibrous layer, a small-cell layer, and a peripheral fibrous capsule including large cells. The GA consists of a central glomerular layer and a peripheral small-cell layer which contains some large cells. Following HRP injections into the GR, HRP-positive cells were found bilaterally in the nucleus corticalis and ipsilaterally in the nucleus intermedius of Bricker ('29). Lesions of the nucleus corticalis produced degenerating terminals bilaterally in glomeruli in the CG. The course of the fiber connections was coincident with that of the commissura horizontalis. Lesions of the nucleus intermedius resulted in degenerating terminals in the fibrous layer of the GR and the small-cell layer of the GA. Following the destruction of the GR, degenerating terminals occurred in the ipsilateral lobus inferior. Both small and large cells in the ipsilateral CG were labeled after HRP injections into the lobus inferior.
These data show that CXCR4 antagonists represent a valuable addition to the cancer therapeutic arsenal. Such agents may have beneficial synergistic dual-effects in reducing tumor cell proliferation directly, and indirectly through perturbation of the tumor microenvironment. Further studies of the novel CTCE-9908 compound in prostate and other solid tumor inhibition are warranted. Prostate 69: 1460-1469, 2009. (c) 2009 Wiley-Liss, Inc.
Cytoarchitecture and fiber connections of the nucleus isthmi in a teleost (Nauodon modestus) were studied by means of Nissl, Bodian, toluidine blue, Golgi, and Fink-Heimer methods. Synaptic terminals were classified by the ultrastructural characteristics, and their origins were determined by electron microscopic degeneration experiments.The nucleus isthmi is composed of an outer cellular area or shell and an inner noncellular area or core. The shell covers anterior, dorsal, and ventral aspects of the core. The cell bodies in the shell are oval (15 x 20 pm) with an anteroposterior long axis, and have many somatic spines. Spines are also seen on the initial segment of the axon. Primary dendrites extend posteromedially and branch out in the core. The core contains thin and thick myelinated fibers, which originate in the optic tectun and in the nucleus pretectalis, respectively.At least two types of axon terminal were distinguished in the nucleus isthmi: S type, containing spherical vesicles, and F type, containing flattened vesicles. S terminals are derived from thin myelinated fibers and are only seen in the core where they form asymmetric synapses with dendrites.Frequently a portion of the S terminal membrane near the usual synaptic cleft is in close apposition with the membrane of an adjacent small dendrite or spine. F terminals, which derived from thick myelinated fibers, make symmetric synaptic contacts with both cell bodies in the shell and dendrites in the core. S terminals degenerate after ipsilateral ablation of the optic tectum, whereas F terminals degenerate after destruction of the nucleus pretectalis.The nucleus isthmi receives a substantial projection from the optic tectum in teleosts (Schroeder, '74 , '76). The nucleus isthmi, in turn, mainly projects to the optic tectum in these vertebrates. From the reciprocal fiber connections, the nucleus isthmi is thought to be homologous to the parabigeminal nucleus of mammals (see Gruberg and Udin, '78). It is also of particular interest that these reciprocal connections are topographically arranged. 300Teleostean isthmic afferent neurons were first identified in Navodon modestus by means of the retrograde horseradish peroxidase (HRP) method (It0 et al., '81). The large pyriform neurons described by Vanegas et al. ('74) were labeled in the optic tectum. The cell body of this type of neuron lies in the upper part of the stratum periventriculare. These neurons are quite similar to those in the pigeon (Hunt et al., '77). Somewhat unexpectedly, neurons of the nucleus pretectalis of Schnitzlein ('62) were also labeled. The nucleus pretectalis receives fibers from the optic tectum but not from the retina (Sakamoto et al., '81). It is obvious from these data that the nucleus isthmi in teleosts receives tectal input via two different pathways: direct tecto-isthmic and indirect tecto-pretecto-isthmic pathways. The indirect pathway has not been demonstrated in other classes of vertebrates. Neurons which constitute the teleostean nucleus pretectalis, therefore,...
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