Bone marrow stromal cells (BMSCs) and osteoclasts (OCs) confer multiple myeloma (MM) cell survival through elaborating factors. We demonstrate herein that IL-6 and TNF family cytokines, TNFα, BAFF ...and APRIL, but not IGF-1 cooperatively enhance the expression of the serine/threonine kinase Pim-2 in MM cells. BMSCs and OCs upregulate Pim-2 expression in MM cells largely via the IL-6/STAT3 and NF-κB pathway, respectively. Pim-2 short interfering RNA reduces MM cell viability in cocultures with BMSCs or OCs. Thus, upregulation of Pim-2 appears to be a novel anti-apoptotic mechanism for MM cell survival. Interestingly, the mammalian target of rapamycin inhibitor rapamycin further suppresses the MM cell viability in combination with the Pim-2 silencing. The Pim inhibitor (Z)-5-(4-propoxybenzylidene) thiazolidine-2, 4-dione and the PI3K inhibitor LY294002 cooperatively enhance MM cell death. The Pim inhibitor suppresses 4E-BP1 phosphorylation along with the reduction of Mcl-1 and c-Myc. Pim-2 may therefore become a new target for MM treatment.
Pim-2 kinase is overexpressed in multiple myeloma (MM) cells to enhance their growth and survival, and regarded as a novel therapeutic target in MM. However, the impact of Pim-2 inhibition on bone ...disease in MM remains unknown. We demonstrated here that Pim-2 expression was also upregulated in bone marrow stromal cells and MC3T3-E1 preosteoblastic cells in the presence of cytokines known as the inhibitors of osteoblastogenesis in MM, including interleukin-3 (IL-3), IL-7, tumor necrosis factor-α, transforming growth factor-β (TGF-β) and activin A, as well as MM cell conditioned media. The enforced expression of Pim-2 abrogated in vitro osteoblastogenesis by BMP-2, which suggested Pim-2 as a negative regulator for osteoblastogenesis. Treatment with Pim-2 short-interference RNA as well as the Pim inhibitor SMI-16a successfully restored osteoblastogenesis suppressed by all the above inhibitory factors and MM cells. The SMI-16a treatment potentiated BMP-2-mediated anabolic signaling while suppressing TGF-β signaling. Furthermore, treatment with the newly synthesized thiazolidine-2,4-dione congener, 12a-OH, as well as its prototypic SMI-16a effectively prevented bone destruction while suppressing MM tumor growth in MM animal models. Thus, Pim-2 may have a pivotal role in tumor progression and bone loss in MM, and Pim-2 inhibition may become an important therapeutic strategy to target the MM cell-bone marrow interaction.
Japanese spotted fever Matsuura, H; Yamauchi, K; Kagawa, K ...
QJM : An International Journal of Medicine,
10/2018, Letnik:
111, Številka:
10
Journal Article
A laser-induced-breakdown-spectroscopy (LIBS) experiment with a unique double-pulse setup and operated in low-pressure (3 kPa) He ambient gas is performed to study the detection of light elements, ...such as hydrogen (H) and deuterium (D), as well as elements of high excitation energies, such as fluorine (F) and chlorine (Cl), which are usually difficult to detect using ordinary LIBS techniques. A nanosecond Nd:YAG laser operated in its fundamental wavelength with energy of 54 mJ is focused onto the Al target to generate the He plasma. Another picosecond Nd:YAG laser operated in its fundamental wavelength with energy of 2 mJ is focused onto the sample surface and activated 2 μs before the operation of the nanosecond laser. The application to polyvinyl chloride (PVC) and polytetrafluoroethylene (PTFE) samples produces sharp and high-intensity Cl- and F-emission lines. Meanwhile, the sharp and well-resolved H–D-emission lines with merely 0.18 nm wavelength separation are also clearly detected from a zircaloy sample. Further measurement of a set of zircaloy samples containing different concentrations of D yields a linear calibration curve with a zero intercept. The detection limit of D is found to be about 10 ppm.
Preprocedural identification of the Adamkiewicz artery is crucial in patients with aortic diseases. This study aimed to compare 70-kV CTA with conventional 120-kV CTA for the identification of the ...Adamkiewicz artery, examining differences in radiation dose and image quality.
We retrospectively analyzed 2 equal groups of 60 patients who had undergone 70-kV or 120-kV CTA to detect the Adamkiewicz artery before aortic repair. Size-specific dose estimate, the CT number of the aorta, and the contrast-to-noise ratio of the anterior spinal artery to the spinal cord were recorded. Furthermore, detectability of the Adamkiewicz artery was evaluated by using a 4-point continuity score (3, definite to 0, undetectable).
There was significantly lower radiation exposure with 70-kV CTA than 120-kV CTA (median size-specific dose estimate, 23.1 versus 61.3 mGy, respectively;
< .001). CT number and contrast-to-noise ratio were both significantly higher in the 70-kV CTA group than the 120-kV group (999.1 HU compared with 508.7 HU, and 5.6 compared with 3.4, respectively;
< .001 for both). Detectability of the Adamkiewicz artery was not impaired in the 70-kV CTA group (90.0% versus 83.3% in the 120-kV group,
= .28). Moreover, the Adamkiewicz artery was detected with greater confidence with 70-kV CTA, reflected by a significantly superior continuity score (median, 3) compared with 120-kV CTA (median, 2;
= .001).
Seventy-kilovolt CTA has substantial advantages for the identification of the Adamkiewicz artery before aortic repair, with a significantly lower radiation exposure and superior image quality than 120-kV CTA.
A major polyphenol of green tea, epigallocatechin-3-gallate (EGCG), has previously been shown to induce cell-cycle arrest and apoptosis in various cancers. However, little is known about its effects ...on hepatocellular carcinomas (HCCs).
Four HCC cell lines, HLE, HepG2, HuH-7 and PLC/PRF/5, were treated with EGCG or vehicle. Cell viability was assessed by trypan blue staining and WST-8 assay. Cell-cycle, apoptosis and apoptosis-related proteins in HLE cells were evaluated by flow cytometry and Western blotting. The effect of EGCG was also studied in vivo using a xenograft model. The effect of co-treatment with EGCG and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) was also assessed.
EGCG inhibited the growth of all HCC cell lines at concentrations of 50–100
μg/ml. In HLE cells, EGCG induced apoptosis but not cell-cycle arrest and appears to have down-regulated Bcl-2α and Bcl-xl by inactivation of NF-κB. Oral administration of EGCG showed similar effects in HLE xenograft tumors. Co-treatment with EGCG and TRAIL synergistically induced apoptosis in HLE cells.
EGCG induced apoptosis in HLE cells, both in vitro and in vivo. Moreover, it enhanced TRAIL-induced apoptosis. Therefore, EGCG treatment may be useful for improving the prognosis of HCCs.
Prior to European contact, Hawaiian cultivators developed and sustained large rain-fed field systems based on sweet potato (Ipomoea batatas) and other crops. However, these intensive systems largely ...were abandoned in the 19th century, and there is little knowledge of how they functioned. Since 2008, we have worked to restore people and production to one such rain-fed field system at Puanui in leeward Kohala on the Island of Hawai’i using traditional knowledge, local knowledge, and experiments to understand how such systems functioned and to provide an educational and cultural resource to local communities. We encountered both climatic and biotic challenges to using traditional knowledge for restoring agricultural production. Climatically, there has been a recent drying trend and a severe 6-yr drought. Biotically, a wide range of weeds, pests, and diseases have been introduced to Hawaii since European contact. Experimental studies of cultivation practices demonstrated that rock mulching, a traditional practice, led to significantly greater yields of sweet potato than did alternative methods. More than 3000 students and community members have participated in the restoration effort and have contributed local and traditional knowledge in the process.
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