Significant association between high serum CCL5 levels and better disease‐free survival of patients with early breast cancer

Analysis of anticancer immunity aids in assessing the prognosis of patients with breast cancer. From 250 operated breast cancers, we focused on serum levels of C‐C motif chemokine ligand 5 (CCL5), which is involved in cancer immune reactions. Serum levels of CCL5 were measured using a cytometric bead‐based immunoassay kit and CCL5 expression in cancer cells was determined using immunohistochemical staining. In addition, mRNA in cancer and stromal cells was analyzed by microdissection and comparison with the public dataset. Disease‐free survival (DFS) of patients with high CCL5 levels (cut‐off, 13.87 ng/mL; n = 192) was significantly better than those with low CCL5 levels (n = 58; hazard ratio, 0.20; 95% confidence interval, 0.10‐0.39; P < .0001). An improved overall survival was observed in patients with high CCL5 levels compared to those with low CCL5 levels (P = .024). On the contrary, high immunohistochemical expression of CCL5 in cancer cells was significantly associated with decreased DFS. As serum CCL5 levels did not correlate with CCL5 expression in cancer cells and the relative expression of mRNA CCL5 was elevated in stromal cells in relation to cancer cells, serum CCL5 might be derived not from cancer cells, but from stromal cells. Expression of CCL5 in serum, but not in cancer cells, might contribute to improved patient prognosis mediating through not only immune reaction, but through other mechanisms. Determination of circulating CCL5 levels could be useful for predicting patient prognosis.     

Central Bisegmentectomy for Malignant Liver Tumors: Experience in 8 Patients

Central bisegmentectomy (CBS) of the liver is an en bloc hepatic resection of Couiaud segments 4, 5, and 8. The indications for CBS include benign and malignant tumors occupying both the left medial and right anterior segments. However, CBS has rarely been reported. Here, we investigate CBS in patients with suboptimal liver function for whom an extended lobectomy is not an optimal solution. Each case was 1 of 8 patients who underwent CBS for hepatocellular carcinoma (HCC) or colorectal cancer liver metastasis (CRLM) at the Department of Surgery, Jikei University Hospital. Indications for CBS consisted of CRLM in 3 patients and HCC in 5 patients. The median duration of operation was 552 minutes, and median blood loss was 2263 g. No postoperative nor in-hospital mortalities occurred. In this study, 1-, 2-, and 3-year disease-free survival rates were 62.5%, 12.5%, and 12.5%, respectively, and 1-, 2-, and 3-year overall survival rates were 100%, 100%, and 85.7%, respectively. CBS is advocated for central liver tumors in patients with suboptimal liver function for whom extended lobectomy could result in less than optimal remnant liver volume and function.Key words: Central bisegmentectomy, Colorectal cancer liver metastasis, Hepatocellular carcinomaCentral bisegmentectomy (CBS) of the liver is an en bloc hepatic resection of Couiaud segments 4, 5, and 8.¹ McBride and Wallace² first reported this procedure in 1972. The indications for CBS include benign and malignant tumors occupying both the left medial and right anterior segments. The traditional procedure for such tumors is extended right or left lobectomy or trisegmentectomy. Because of the possibility of conservation of remnant liver parenchymal volume, CBS may be superior to extended lobectomy or trisegmentectomy, especially for patients with low residual liver function due to viral hepatitis or adjuvant chemotherapy. However, CBS has rarely been reported. We herein report our experience with 8 patients who underwent CBS for colorectal cancer liver metastasis (CRLM) or hepatocellular carcinoma (HCC).     

Alteration in stress distribution patterns through the elbow joint in professional and college baseball pitchers: Using computed tomography osteoabsorptiometry

Background

Long-term pitching activities change the stress distribution across the elbow joint surface in living subjects, however the influence of the different strength of stress on the stress distribution patterns remain unclear. The aims of this study were to evaluate the distribution of subchondral bone density across the elbow joint in different levels of pitchers, and to reveal the influence of the strength of stress on the elbow joint surface under long-term loading conditions of baseball pitching.

Serum procalcitonin as a predictor of infectious complications after pancreaticoduodenectomy: review of the literature and our experience

Surgery Today - Procalcitonin (PCT) is an early predictor of bacterial infection. We reviewed the literature and analyzed data on our own patients to assess the value of PCT as a predictor of...     

Evidence for neurogenesis in the adult mammalian substantia nigra

New neurons are generated from stem cells in a few regions of the adult mammalian brain. Here we provide evidence for the generation of dopaminergic projection neurons of the type that are lost in Parkinson's disease from stem cells in the adult rodent brain and show that the rate of neurogenesis is increased after a lesion. The number of new neurons generated under physiological conditions in substantia nigra pars compacta was found to be several orders of magnitude smaller than in the granular cell layer of the dentate gyrus of the hippocampus. However, if the rate of neuronal turnover is constant, the entire population of dopaminergic neurons in substantia nigra could be replaced during the lifespan of a mouse. These data indicate that neurogenesis in the adult brain is more widespread than previously thought and may have implications for our understanding of the pathogenesis and treatment of neurodegenerative disorders such as Parkinson's disease.     

Interleukin-18 (Interferon-γ–inducing Factor) Is Produced by Osteoblasts and Acts Via Granulocyte/Macrophage Colony-stimulating Factor and Not Via Interferon-γ to Inhibit Osteoclast Formation

We have established by differential display polymerase chain reaction of mRNA that interleukin (IL)-18 is expressed by osteoblastic stromal cells. The stromal cell populations used for comparison differed in their ability to promote osteoclast-like multinucleated cell (OCL) formation. mRNA for IL-18 was found to be expressed in greater abundance in lines that were unable to support OCL formation than in supportive cells. Recombinant IL-18 was found to inhibit OCL formation in cocultures of osteoblasts and hemopoietic cells of spleen or bone marrow origin. IL-18 inhibited OCL formation in the presence of osteoclastogenic agents including 1α,25-dihydroxyvitamin D₃, prostaglandin E₂, parathyroid hormone, IL-1, and IL-11. The inhibitory effect of IL-18 was limited to the early phase of the cocultures, which coincides with proliferation of hemopoietic precursors. IL-18 has been reported to induce interferon-γ (IFN-γ) and granulocyte/macrophage colony-stimulating factor (GM–CSF) production in T cells, and both agents also inhibit OCL formation in vitro. Neutralizing antibodies to GM–CSF were able to rescue IL-18 inhibition of OCL formation, whereas neutralizing antibodies to IFN-γ did not. In cocultures with osteoblasts and spleen cells from IFN-γ receptor type II–deficient mice, IL-18 was found to inhibit OCL formation, indicating that IL-18 acted independently of IFN-γ production: IFN-γ had no effect in these cocultures. Additionally, in cocultures in which spleen cells were derived from receptor-deficient mice and osteoblasts were from wild-type mice and vice versa, we identified that the target cells for IFN-γ inhibition of OCL formation were the hemopoietic cells. The work provides evidence that IL-18 is expressed by osteoblasts and inhibits OCL formation via GM–CSF production and not via IFN-γ production.     

Malaria parasites giving rise to recrudescence in vitro

Recrudescences were simulated in vitro with drug treatment to examine how drug-sensitive parasites survive the treatment. Various numbers of cultured parasites were treated with lethal doses of pyrimethamine or mefloquine for various lengths of time. Recrudescences were observed in parasite populations with larger initial numbers of parasites when the treatment duration was prolonged. Equal numbers of parasitized erythrocytes were treated with various concentrations of pyrimethamine or mefloquine. There was no clear linear relationship between the incidence of recrudescence and the drug concentration. Parasites that had recrudesced were continuously allowed to recrudesce in the succeeding recrudescence experiments. Both the duration from the cessation of treatment to the time at which the recrudescent parasitemia level reached 1% and the growth rate of recrudescent parasites were equal among these recrudescences. The recrudescent parasites in these experiments were as sensitive to the drugs as the parasites tested before treatment were. These results suggest that a parasite culture may contain parasites in some phases that are not killed by drug for up to 10 days, which explains the recrudescences that occur even after treatment.     

A role for IL-18 in human neutrophil apoptosis

Decreased neutrophil apoptosis is associated with persistent inflammation, the severity of which correlates with serum IL-18 levels. IL-18 receptors as well as Toll-like receptors, including Toll-like receptor 4, a receptor for LPS, possess a highly conserved intracellular domain called "Toll-IL-1R domain" and activate overlapping signaling pathways. Here, we show that IL-18 modulates neutrophil apoptosis and compare its mechanism of action with LPS. We found that both IL-18 and LPS decreased neutrophil apoptosis in a similar dose- and time-dependent fashion. However, pretreatment with the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 increased apoptosis more effectively in IL-18- than in LPS-stimulated cells, whereas the ERK inhibitor PD98059 had the same effect in both. In contrast, the p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580 had no influence on apoptosis at all. Neutrophils constitutively expressed mRNA for IL-18 receptor beta, but little or no receptor alpha, both of which increased during coculture with either IL-18 or LPS in a time- and dose-dependent manner. Of the Bcl-2 family, antiapoptotic A1/Bfl-1 tended to increase on IL-18 and LPS stimulation, but was further increased despite increased apoptosis in the presence of MAPK inhibitors. Thus, human neutrophils can express mRNA for IL-18 receptors alpha and beta, and IL-18, like LPS, inhibits neutrophil apoptosis by activating PI3K and ERK pathways but not p38MAPK. However, PI3K may play more important role(s) in IL-18- than in LPS-induced inhibition of apoptosis. Mitogen-activated protein kinases seem to mediate antiapoptotic signals through factors other than Bcl-2 gene family expression.