Fibrinogen regulates the cytotoxicity of mycobacterial trehalose dimycolate, but is not required for cell recruitment, cytokine response, or control of mycobacterial infection

During inflammatory responses and wound healing, the conversion of soluble fibrinogen to fibrin, an insoluble extracellular matrix, long has been assumed to create a scaffold for the migration of leukocytes and fibroblasts. Previous studies concluded that fibrinogen is a necessary cofactor for mycobacterial trehalose 6,6-dimycolate-induced responses, because trehalose dimycolate-coated beads, to which fibrinogen was ad-sorbed, were more inflammatory than those to which other plasma proteins were adsorbed. Herein, we investigate roles for fibrin(ogen) in an in vivo model of mycobacterial granuloma formation and in infection with Mycobacterium tuberculosis, the causative agent of tuberculosis. In wild-type mice, the subcutaneous injection of trehalose dimycolate-coated polystyrene microspheres, suspended within Matrigel, elicited a pyogranulomatous response during the course of 12 days. In fibrinogen-deficient mice, neutrophils were recruited but a more suppurative lesion developed, with the marked degradation and disintegration of the matrix. Compared to that in wild-type mice, the early formation of granulation tissue in fibrinogen-deficient mice was edematous, hypocellular, and disorganized. These deficiencies were complemented by the addition of exogenous fibrinogen. The absence of fibrinogen had no effect on cell recruitment or cytokine production i

Apoptotic effect of IP6 was not enhanced by co-treatment with myo-inositol in prostate carcinoma PC3 cells

Inositol hexaphosphate (IP6) is a major constituent of most cereals, legumes, nuts, oil seeds and soybean. Previous studies reported the anticancer effect of IP6 and suggested that co-treatment of IP6 with inositol may enhance anticancer effect of IP6. Although the anticancer effect of IP6 has been intensively studied, the combinational effect of IP6 and inositol and involved mechanisms are not well understood so far. In the present study, we investigated the effect of IP6 and myo-inositol (MI) on cell cycle regulation and apoptosis using PC3 prostate cancer cell lines. When cells were co-treated with IP6 and MI, the extent of cell growth inhibition was significantly increased than that by IP6 alone. To identify the effect of IP6 and MI on apoptosis, the activity of caspase-3 was measured. The caspase-3 activity was significantly increased when cells were treated with either IP6 alone or both IP6 and MI, with no significant enhancement by co-treatment. To investigate the effect of IP6 and MI of cell cycle arrest, we measured p21 mRNA expression in PC3 cells and observed significant increase in p21 mRNA by IP6. But synergistic regulation by co-treatment with IP6 and MI was not observed. In addition, there was no significant effect by co-treatment compared to IP6 treatment on the regulation of cell cycle progression although IP6 significantly changed cell cycle distribution in the presence of MI or not. Therefore, these findings support that IP6 has anticancer function by induction of apoptosis and regulation of cell cycle. However, synergistic effect by MI on cell cycle regulation and apoptosis was not observed in PC3 prostate cancer cells

Germline polymorphisms as modulators of cancer phenotypes

Identifying the complete repertoire of genes and genetic variants that regulate the pathogenesis and progression of human disease is a central goal of post-genomic biomedical research. In cancer, recent studies have shown that genome-wide association studies can be successfully used to identify germline polymorphisms associated with an individual's susceptibility to malignancy. In parallel to these reports, substantial work has also shown that patterns of somatic alterations in human tumors can be successfully employed to predict disease prognosis and treatment response. A paper by Van Ness et al. published this month in BMC Medicine reports the initial results of a multi-institutional consortium for multiple myeloma designed to evaluate the role of germline polymorphisms in influencing multiple myeloma clinical outcome. Applying a custom-designed single nucleotide polymorphism microarray to two separate patient cohorts, the investigators successfully identified specific combinations of germline polymorphisms significantly associated with early clinical relapse. These results raise the exciting possibility that besides somatically acquired alterations, germline genetic background may also exert an important influence on cancer patient prognosis and outcome. Future 'personalized medicine' strategies for cancer may thus require incorporating genomic information from both tumor cells and the non-malignant patient genome

Analysis of spontaneous regeneration of olfactory structures with emphasis on myelination and re-innervation of cortical areas

Regeneration of the lateral olfactory tract (LOT) occurs spontaneously after transection in developing rats. In neonatally LOT-transected rats, we observed a newly formed myelinated tract near the rhinal sulcus. The aim of this study was to analyze the precise re-innervated cortical areas and to demonstrate ectopic LOT myelination in neonatally LOT-transected rats. Neonatal rats were subjected to unilateral LOT transection and simultaneous injection of a retrograde fluorescent tracer into the posterior olfactory cortex to evaluate the degree of transection. After 8 weeks, bilateral olfactory bulbs of the rats were subjected to multiple injections of an anterograde neuronal tracer to determine the extent of the regenerated fibers. In the completely LOT-transected rats, the regenerated fibers were distributed in the anterior olfactory cortices: the anterior olfactory nucleus, the olfactory tubercle, and the rostral part of the piriform cortex. Ectopic myelination of LOT was evident immediately below the rhinal sulcus in the completely and incompletely LOT-transected rats. We concluded that the regenerated bulbar fibers were confined to the regions of the anterior olfactory cortices and that ectopic myelination of the regenerated LOT occurred only at a specific site near the rhinal sulcus.ArticleNEUROSCIENCE LETTERS. 537:35-39 (2013)journal articl

Stereotactic Body Radiotherapy for Isolated Para-aortic Lymph Node Recurrence after Curative Resection in Gastric Cancer

The aim of this study was to investigate whether stereotactic body radiotherapy (SBRT) can salvage gastric cancer patients with para-aortic lymph node (PALN) recurrence. From January 2003 to December 2006, 7 patients were treated for isolated PALN recurrence from gastric cancer after curative resection. Follow up durations ranged from 19 to 33 months (median; 26 months), and SBRT doses from 45 Gy to 51 Gy (median 48 Gy) in 3 fractions. Disease progression-free and overall survivals and toxicities were recorded. Response to treatment was assessed by computed tomography. Final patient outcomes were as follows: 2 were alive without evidence of disease, 3 remained alive with disease, and 2 patients died of disease. Five of 7 patients showed complete response and 2 patients partial response between 3 and 11 months after SBRT. Three-year overall and disease progression-free survival rates post-SBRT were 43% and 29%, respectively. No severe complication was detected during follow-up. Selected patients with isolated PALN recurrence can be salvaged by SBRT without severe complications