Interleukin-28B acts synergistically with cisplatin to suppress the growth of head and neck squamous cell carcinoma

Interleukin-28B (IL-28B), also referred to as interferon-λ3, belongs to the type III interferon family. Earlier studies showed that IL-28B suppresses proliferation of some tumor cells in vitro. IL-28B gene transfection ex vivo also resulted in growth retardation of tumor cells in mice, through either direct antiproliferative action or induction of antitumor immunity. However, it has not been reported whether in vivo therapeutic administration of recombinant IL-28B can inhibit the growth of a pre-established tumor. Here, we found that repetitive subcutaneous administration of recombinant mouse IL-28B significantly induced tumor-specific cytotoxic T lymphocytes and augmented natural killer cytolytic activity, leading to moderate suppression of the growth of a murine head and neck squamous cell carcinoma (HNSCC) cell line that was completely resistant to the direct antiproliferative effect of IL-28B. Moreover, co-administration of recombinant mouse IL-28B and cisplatin (CDDP) more significantly inhibited in vivo growth of the tumor that had been established in syngenic mice and induced tumor-specific cytotoxic T lymphocytes. The CDDP treatment induced the expression of major histocompatibility complex class I and Fas molecules on the surface of HNSCC cells both in vitro and in vivo; this may be the mechanism underlying the synergistic tumor suppression activity of IL-28B and CDDP. Unlike type I interferon, IL-28B did not suppress growth of bone marrow cells in culture. Therefore, IL-28B may be useful as a tool for a novel multidisciplinary therapy against cancer, significantly potentiating innate and adaptive antitumor immune responses, especially when co-administrated with CDDP, which is currently the first choice chemotherapeutic agent against various tumors including HNSCCs.     

Maridomycin, a New Macrolide Antibiotic: In Vivo Antibacterial Activity of 9-Propionylmaridomycin

The in vivo protecting activity of 9-propionylmaridomycin, a derivative of the new macrolide antibiotic, maridomycin, was compared with that of other macrolide antibiotics in mice infected with Staphylococcus aureus, Streptococcus pyogenes, and Diplococcus pneumoniae. The protective effect was almost similar to that afforded by several known macrolide antibiotics in mice infected intraperitoneally with certain strains of the gram-positive species described above. The skin lesion caused by intradermal challenge of S. aureus in mice also responded very effectively to treatment with 9-propionylmaridomycin.     

Maridomycin, a New Macrolide Antibiotic. In Vitro Antibacterial Activity of 9-Propionylmaridomycin

9-Propionylmaridomycin shows in vitro antibacterial activity against gram-positive bacteria and has some action on Neisseria gonorrhoeae and Vibrio cholerae, but is generally inactive against many gram-negative rods. This antibiotic exhibits strong activity against clinical isolates of Staphylococcus aureus which are highly resistant to erythromycin or oleandomycin, or both, but which are sensitive to josamycin and kitasamycin. Strains resistant to josamycin and kitasamycin were also found to be resistant to this antibiotic. A significant feature of 9-propionylmaridomycin is a lack in its ability to induce resistance induction in resistance-inducible strains of staphylococci to erythromycin. Several antibacterial features of 9-propionylmaridomycin such as the influence of medium pH, inoculum size, effect of addition of horse serum, development of resistance, cross resistance, and bacteriostatic activity were shown to be almost identical to those of josamycin and kitasamycin. The antibacterial activity of 9-propionylmaridomycin was stable in solutions at pH levels of 4, 7, and 9.     

Tumor necrosis factor receptor regulation of bone marrow cell apoptosis during endotoxin-induced systemic inflammation

Although inflammation-induced release of cells from the bone marrow (BM) is well established, less is known regarding inflammation-induced modulation of bone marrow cell numbers by apoptosis. The purpose of this study is to assess apoptosis of BM immature and mature myeloid cells and peripheral granulocytes, and to elucidate the role(s) of TNFR-p55 and TNFR-p75 as modulators of apoptosis in these cellular compartments in a mouse model of endotoxin-induced systemic inflammation. Gene knockout (p55(-/-), p75(-/-), and p55(-/-)/p75(-/-)), or wild-type (WT) mice were injected i.p. with saline (Sal) or LPS (4 microg/g) followed by collection of BM cells and peripheral blood after 24 h. Apoptosis was assessed by propidium iodide staining using two-color flow cytometry with differentiated granulocyte-specific Gr1-fluorescein isothiocyanate. Repeated-measures analysis of variance and Neuman-Keuls post hoc test were used for statistical analyses. After i.p. LPS, apoptosis was induced to the higher level in BM Gr1(-) cells than in BM Gr1(+) cells and was not induced in peripheral Gr1(+) cells. Depletion of cell numbers in both BM Gr1(-) and Gr1(+) subpopulations after LPS treatment was consistent with increase of the apoptotic cell percentages in the groups. LPS-induced apoptosis was significantly lower in Gr1(-) cells from the -p55(-/-)/LPS and p55(-/-)/p75(-/-)/LPS mice but not from p75(-/-)/LPS mice as compared with WT/LPS mice, whereas there was no difference in apoptosis of BM Gr1(+) and peripheral Gr1(+) cells among WT groups and knockout groups. Thus, apoptosis of myeloid cells during endotoxemia is minimized because these cells undergo differentiation, which in turn may be because of the attenuation of the proapoptotic effect of TNFR-p55 shown herein to occur with myeloid differentiation. In contrast, TNFR-p75 seems to play a minimal role in apoptosis induction in Gr1(-) myeloid cells during endotoxemia. One explanation for a decrease in BM cell numbers during endotoxemia may be via induction of apoptosis in immature myeloid cells.     

Pharmacokinetic analysis based on dynamic contrast-enhanced MRI for evaluating tumor response to preoperative therapy for oral cancer

Purpose:

To evaluate whether a pharmacokinetic analysis is useful for monitoring the response of oral cancer to chemoradiotherapy (CRT).

Materials and Methods:

Twenty‐nine patients were included. They underwent dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) before and after CRT. The DCE‐MRI data were analyzed using a Tofts and Kermode (TK) model. The histological evaluation of the effects of CRT was performed according to Ohboshi and Shimosato's classification.

Results:

None of the pre‐CRT parameters were significantly different between the responders and nonresponders. The post‐CRT volume of the extravascular extracellular space (EES) per unit volume of tissue (v_e) of responders (0.397 ± 0.080) was higher than that of nonresponders (0.281 ± 0.076) (P = 0.01). The change of the v_e between the pre‐ and post‐CRT of the responders (0.154 ± 0.093) was larger than that of the nonresponders (0.033 ± 0.073) (P = 0.001). Therefore, the increase in the v_e strongly suggested a good tumor response to CRT, which reflected an increase of the EES secondary to the destruction of the cancer nest. The changes in the volume transfer constant (K^trans) were significantly different between the responders and nonresponders (P = 0.018).

Conclusion:

Both the increase of the v_e and the elevation of permeability (K^trans) were indicative of a good tumor response to CRT. The pharmacokinetic analysis had potential for monitoring the histopathological response to CRT. J. Magn. Reson. Imaging 2012;36:589–597. © 2012 Wiley Periodicals, Inc.     

Radiological findings of primary localized amyloidosis of the ureter

Localized amyloidosis is a rare condition, especially that involving the ureter. Because of its rarity and the difficulty in differentiating this condition from urothelial carcinoma by intravenous urography and computed tomography, nephroureterectomy has often been performed unnecessarily for this disease. The authors encountered two cases of this disease, both of which showed a negative urine cytology, no obvious mass effect, and a hypointensity on T2-weighted imaging. Because these findings are very rare in urothelial carcinoma, ureteroscopy-guided biopsy was performed, which yielded the diagnosis of amyloidosis. The patients were then treated and followed up at our institute. Primary localized amyloidosis of the ureter should be considered when evaluating ureteric lesions visualized as hypointensities on T2-weighted images that do not show an obvious mass effect, which could help in the avoidance of unnecessary surgery.     

Magnetic resonance spectroscopy and its clinical applications in multiple sclerosis

Proton magnetic resonance spectroscopy(1H-MRS), which provides biochemical information in not only visible lesions on conventional MR imaging but also normal appearing white matter(NAWM), has extended the genesis of multiple sclerosis(MS) in several important directions. First, serial 1H-MRS studies reveal dynamic regional biochemical alterations in plaques during the course of the illness. Second, axonal damage may occur at early stage. Third, neuronal loss can be substantial in the gray matter. Fourth, NAWM shows widespread biochemical involvement prior to detection on MRI. Fifth, severities of neuroaxonal involvement significantly correlate with neurological dysfunction. 1H-MRS will provide more detailed information than conventional MRI, and could be beneficial in monitoring effects of therapeutic interventions in MS.     

Recent Insights into Clostridium perfringens Beta-Toxin

Clostridium perfringens beta-toxin is a key mediator of necrotizing enterocolitis and enterotoxemia. It is a pore-forming toxin (PFT) that exerts cytotoxic effect. Experimental investigation using piglet and rabbit intestinal loop models and a mouse infection model apparently showed that beta-toxin is the important pathogenic factor of the organisms. The toxin caused the swelling and disruption of HL-60 cells and formed a functional pore in the lipid raft microdomains of sensitive cells. These findings represent significant progress in the characterization of the toxin with knowledge on its biological features, mechanism of action and structure-function having been accumulated. Our aims here are to review the current progresses in our comprehension of the virulence of C. perfringens type C and the character, biological feature and structure-function of beta-toxin.