Arsenic is a unique element with distinct physical characteristics and toxicity whose importance in public health is well recognized. The toxicity of arsenic varies across its different forms. While the carcinogenicity of arsenic has been confirmed, the mechanisms behind the diseases occurring after acute or chronic exposure to arsenic are not well understood. Inorganic arsenic has been confirmed as a human carcinogen that can induce skin, lung, and bladder cancer. There are also reports of its significant association to liver, prostate, and bladder cancer. Recent studies have also suggested a relationship with diabetes, neurological effects, cardiac disorders, and reproductive organs, but further studies are required to confirm these associations. The majority of research to date has examined cancer incidence after a high exposure to high concentrations of arsenic. However, numerous studies have reported various health effects caused by chronic exposure to low concentrations of arsenic. An assessment of the health effects to arsenic exposure has never been performed in the South Korean population; thus, objective estimates of exposure levels are needed. Data should be collected on the biological exposure level for the total arsenic concentration, and individual arsenic concentration by species. In South Korea, we believe that biological exposure assessment should be the first step, followed by regular health effect assessments.
Brain metastasis in breast cancer is particularly deadly, but effective treatments remain out of reach due to insufficient information about the mechanisms underlying brain metastasis and the potential vulnerabilities of brain-metastatic breast cancer cells. Here, human breast cancer cells and their brain-metastatic derivatives (BrMs) were used to investigate synthetic lethal interactions in BrMs. First, it was demonstrated that c-MYC activity is increased in BrMs and is required for their brain-metastatic ability in a mouse xenograft model. Specifically, c-MYC enhanced brain metastasis by facilitating the following processes within the brain microenvironment: (i) invasive growth of BrMs, (ii) macrophage infiltration, and (iii) GAP junction formation between BrMs and astrocytes by upregulating connexin 43 (GJA1/Cx43). Furthermore, RNAsequencing (RNA-seq) analysis uncovered a set of c-MYC-regulated genes whose expression is associated with higher risk for brain metastasis in breast cancer patients. Paradoxically, however, increased c-MYC activity in BrMs rendered them more susceptible to TRAIL (TNF-related apoptosisinducing ligand)-induced apoptosis. In summary, these data not only reveal the brain metastasis-promoting role of c-MYC and a subsequent synthetic lethality with TRAIL, but also delineate the underlying mechanism. This suggests TRAIL-based approaches as potential therapeutic options for brain-metastatic breast cancer.Implications: This study discovers a paradoxical role of c-MYC in promoting metastasis to the brain and in rendering brainmetastatic cells more susceptible to TRAIL, which suggests the existence of an Achilles' heel, thus providing a new therapeutic opportunity for breast cancer patients.
PURPOSEThe purpose of this study was to compare the accuracy of the implant master cast according to the type (pick-up, transfer) and the length (long, short) of the impression copings.MATERIALS AND METHODSThe metal master cast was fabricated with three internal connection type implant analogs (Osstem GS III analog), embedded parallel and with 10° of mesial angulation to the center analog. Four types of impression coping were prepared with different combinations of types (transfer, pick-up) and lengths (long, short) of the coping. The impressions were made using vinyl polysiloxane (one step, heavy + light body) with an individual tray, and 10 impressions were made for each group. Eventually, 40 experimental casts were produced. Then, the difference in the distance between the master cast and the experimental cast were measured, and the error rate was determined. The analysis of variance was performed using the SPSS (v 12.0) program (α = .05), and the statistical significance was set at P < .05.RESULTSThe ANOVA showed that the pick-up type impression coping exhibited a significantly lower error rate than the transfer type. However, no significant difference was observed with respect to the length of the impression coping. Additionally, no significant difference was observed between the parallel and mesial angulated groups.CONCLUSIONWithin the limitations of this study, the pick-up type impression coping exhibited a more accurate implant master cast than the transfer type in parallel group. The accuracy of the implant master cast did not differ for different lengths of impression coping of at least 11 mm. Additionally, the accuracy of the implant cast was not different for the parallel and 10° mesial angulated groups.
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