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Ionizing radiation (IR) is an important means of tumor treatment in addition to surgery and drugs. Attempts have been made to improve the efficiency of radiotherapy by identifying the various biological effects of IR on cells. Components of the tumor microenvironment, such as macrophages, fibroblasts, and vascular endothelial cells, influence cancer treatment outcomes through communication with tumor cells. In this study, we found that IR selectively increased the production of CXC motif chemokine ligand 10 (CXCL10), which is emerging as an important biomarker for determining the prognosis of anticancer treatments, without changing the levels of CXCL9 and CXCL11 in murine J774A.1 macrophages. Pretreatment with KU55933, an ataxia telangiectasia mutated (ATM) kinase inhibitor, significantly inhibited IR-induced CXCL10 production. In contrast, pretreatment with N-acetyl-cysteine or glutathione, a reactive oxygen species scavenger, did not inhibit IR-induced CXCL10 production. Further, we attempted to identify the intracellular molecular target associated with the IR-induced increase in CXCL10 secretion by J774A.1 macrophages. IR phosphorylated p38 mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription 1 (STAT1) in J774A.1 macrophages, and p38 MAPK and STAT1 were involved in CXCL10 via IR using pharmacological inhibitors (SB203580 and fludarabine, respectively) and the siRNA technique.

Macrophages are abundant immune cells in the tumor microenvironment and are crucial in regulating tumor malignancy. We previously reported that ionizing radiation (IR) increases the production of interleukin (IL)-1β in lipopolysaccharide (LPS)-treated macrophages, contributing to the malignancy of colorectal cancer cells; however, the mechanism remained unclear. Here, we show that IR increases the activity of cysteine-aspartate-specific protease 1 (caspase-1), which is regulated by the inflammasome, and cleaves premature IL-1β to mature IL-1β in RAW264.7 macrophages. Irradiated RAW264.7 cells showed increased expression of NLRC4 inflammasome, which controls the activity of caspase-1 and IL-1β production. Silencing of NLRC4 using RNA interference inhibited the IR-induced increase in IL-1β production. Activation of the inflammasome can be regulated by mitogen-activated protein kinase (MAPK)s in macrophages. In RAW264.7 cells, IR increased the phosphorylation of p38 MAPK but not extracellular signal-regulated kinase and c-Jun N-terminal kinase. Moreover, a selective inhibitor of p38 MAPK inhibited LPS-induced IL-1β production and NLRC4 inflammasome expression in irradiated RAW264.7 macrophages. Our results indicate that IR-induced activation of the p38 MAPK-NLRC4-caspase-1 activation pathway in macrophages increases IL-1β production in response to LPS.

This study investigated the inhibitory effect of ginsenoside-Rp1 (G-Rp1) on the ionizing radiation (IR)-induced response in lipopolysaccharide (LPS)-stimulated macrophages and its effects on the malignancy of tumor cells. G-Rp1 inhibited the activation of IR-induced DNA damage-related signaling molecules and thereby interfered with the IR-increased production of nitric oxide (NO) and interleukin (IL)-1β. The inhibitory effect of G-Rp1 increased the survival rate of mice inoculated with CT26 colon cancer cells by suppressing the phenotypic variation of tumor cells induced by conditioned medium obtained from IR- and LPS-treated J774A.1 macrophages., Competing Interests: All authors have no competing interests to declare., (© 2020 The Korean Society of Ginseng. Publishing services by Elsevier B.V.)

Objective: Posterior apophyseal ring fracture (PARF) is a common disorder that may be accompanied by herniated lumbar disc (HLD) in patients in their early twenties. However, there are very few reports on PARF in this clinical context. The objective of this study was to identify the incidence and characteristics of PARF with HLD in this age group., Methods: We surveyed patients who visited Armed Forces Busan Hospital between May 2017 and October 2017 and included those aged between 19 and 25 years who had HLD accompanied by PARF. We retrospectively collected their demographic characteristics, clinical manifestations, and radiological findings on computed tomography (CT) scans. We categorized the PARF lesions according to Takata's classification., Results: Of 140 HLD patients, 43 (30.7%) had PARF lesions with HLD. We found that the presence of a PARF lesion was significantly related to a severe pain score on the visual analogue scale for lower back pain and/or lower leg radiating pain (p=0.001). The most common level and location of PARF were L5/S1 (n=25, 56.8%) and the superior endplate of the S1 vertebra, respectively. Type 1, according to Takata's classification, was the most common type of PARF in the patients (n=34, 77.2%)., Conclusion: We recommend that spinal surgeons perform CT scans to check for PARF lesions in all young patients in their 20s who present with severe radiating and lower back pain.

Pig-human xenotransplantation can trigger cell-mediated immune responses. We explored the role of gangliosides in inflammation related to immune rejection in xenotransplantation. Co-culture of xenogeneic cells (pig-MSCs and RAW264.7) was used to emulate xenotransplantation conditions. MTT assay results indicated that cell viability was significantly decreased in pADMSCs co-cultured with RAW264.7 cells. GM1 and GM3 were highly expressed in pADMSCs co-cultured with RAW264.7 cells. pADMSCs co-cultured with RAW264.7 cells strongly expressed pro-inflammatory proteins such as COX-2, iNOS, p50, p65, pIκBα, and TNF-α. GM1-knockdown pADMSCs co-cultured with RAW 264.7 cells did not show significantly altered cell viability, but pro-inflammatory proteins were markedly inhibited. Co-culture of pADMSCs with RAW264.7 cells induced significant phosphorylation (p) of JNK1/2 and pERK1/2. However, pERK1/2 and pJNK1/2 were decreased and MEK1/2 and Raf1 were suppressed in GM1-knockdown pADMSCs co-cultured with RAW264.7 cells. Thus, the Raf-1/MEK1/2/ERK1/2 and JNK1/2 pathways were significantly upregulated in response to increases of GM1 in co-cultured xenogeneic cells. However, the inflammatory response was suppressed in co-culture of GM1-knockdown pADMSCs with RAW264.7 cells via down-regulation of the Raf-1/MEK1/2/ERK1/2 and JNK1/2 pathways. Therefore, the ganglioside GM1 appears to play a major role in the inflammatory response in xenotransplantation via the Raf-1/MEK1/2/ERK1/2 and JNK1/2 pathways.

Fibromatosis refers to an extra-abdominal desmoid tumor or aggressive fibromatosis. Breast fibromatosis can develop in association with the capsule around a breast implant, although reports of cases of fibromatosis associated with breast implants are rare. As the demand for breast augmentation has increased, it is important to understand the diseases associated with breast implants. In the present report, we describe a case of breast fibromatosis that developed adjacent to a breast implant and demonstrated a relatively well-defined border even though it invaded the surrounding structures. We also explore the specific imaging features for diagnosing breast fibromatosis in association with implants by reviewing previous literature.

Neurofibromatosis type 1 (NF1) is one of the most common genetic diseases in humans and is associated with various benign and malignant tumors, including breast cancer. However, an increased risk of breast cancer in NF1 patients has not been widely recognized or accepted. Here, we report two cases of breast cancer in NF1 patients and review the literature on the association between NF1 and breast cancer.

Cell invasion and migration that occurs, for example, in cancer metastasis is rooted in the ability of cells to navigate through varying levels of physical constraint exerted by the extracellular matrix. Cancer cells can invade matrices in either a protease-independent or a protease-dependent manner. An emerging critical component that influences the mode of cell invasion is the traction stresses generated by the cells in response to the physicostructural properties of the extracellular matrix. In this study, we have developed a reference-free quantitative assay for measuring three-dimensional (3D) traction stresses generated by cells during the initial stages of invasion into matrices exerting varying levels of mechanical resistance. Our results show that as cells encounter higher mechanical resistance, a larger fraction of them shift to protease-mediated invasion, and this process begins at lower values of cell invasion depth. On the other hand, the compressive stress generated by the cells at the onset of protease-mediated invasion is found to be independent of matrix stiffness, suggesting that 3D traction stress is a key factor in triggering protease-mediated cancer cell invasion. At low 3D compressive traction stresses, cells utilize bleb formation to indent the matrix in a protease independent manner. However, at higher stress values, cells utilize invadopodia-like structures to mediate protease-dependent invasion into the 3D matrix. The critical value of compressive traction stress at the transition from a protease-independent to a protease-dependent mode of invasion is found to be ∼165 Pa., (Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

A heparin-binding peptide (HBP) sequence from human heparin-binding epidermal growth factor-like growth factor (HB-EGF) was identified and was shown to exhibit cell penetration activity. This cell penetration induced an anti-inflammatory reaction in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages. HBP penetrated the cell membrane during the 10 min treatment and reduced the LPS-induced production of nitric oxide (NO), inducible nitric oxide synthase (iNOS), and cytokines (TNF-α and IL-6) in a concentration-dependent manner. Additionally, HBP inhibited the LPS-induced upregulation of cytokines, including TNF-α and IL-6, and decreased the interstitial infiltration of polymorphonuclear leukocytes in a lung inflammation model. HBP inhibited NF-κB-dependent inflammatory responses by directly blocking the phosphorylation and degradation of IκBα and by subsequently inhibiting the nuclear translocation of the p65 subunit of NF-κB. Taken together, this novel HBP may be potentially useful candidate for anti-inflammatory treatments and can be combined with other drugs of interest to transport attached molecules into cells., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Benz[a]anthracene is a ubiquitous environmental contaminant formed during the incomplete combustion of organic material. Some of the metabolites of benz[a]anthracene are known to be toxic and carcinogenic. In this investigation, benz[a]anthracene-induced oxidative damage to lymphocyte DNA was evaluated with the Comet assay (single cell gel electrophoresis). The level of oxidative DNA damage caused by benz[a]anthracene increased in a dose-dependent manner (24, 49) and oxidative DNA damage was significantly inhibited by 5 and 10 microg ml(-1) ascorbate, 5 microg ml(-1) polyphenols, as well as 5 and 10 microg ml(-1) curcumin. Moreover, traditional Korean medicinal herbs such as Acanthopanax and ginseng significantly reduced DNA damage. The results demonstrate that antioxidant supplementation to lymphocytes inhibits oxidative DNA damage in vitro, supporting an inhibitory effect against oxidative DNA damage, probably due to reduction of reactive oxygen species production induced by benz[a]anthracene.