Locally produced osteoclastogenic factor RANKL plays a critical role in the development of bone resorption in periradicular periodontitis. However, because RANKL is also required for healthy bone ...remodeling, it is plausible that a costimulatory molecule that upregulates RANKL production in inflammatory periradicular periodontitis may be involved in the pathogenic bone loss processes. We hypothesized that macrophage migration inhibitory factor (MIF) would play a role in upregulating the RANKL-mediated osteoclastogenesis in the periradicular lesion. In response to pulp exposure, the bone loss and level of MIF mRNA increased in the periradicular periodontitis, which peaked at 14 d, in conjunction with the upregulated expressions of mRNAs for RANKL, proinflammatory cytokines (TNF-α, IL-6, and IL-1β), chemokines (MCP-1 and SDF-1), and MIF's cognate receptors CXCR4 and CD74. Furthermore, expressions of those mRNAs were found significantly higher in wild-type mice compared with that of MIF
mice. In contrast, bacterial LPS elicited the production of MIF from ligament fibroblasts in vitro, which, in turn, enhanced their productions of RANKL and TNF-α. rMIF significantly upregulated the number of TRAP
osteoclasts in vitro. Finally, periapical bone loss induced in wild-type mice were significantly diminished in MIF
mice. Altogether, the current study demonstrated that MIF appeared to function as a key costimulatory molecule to upregulate RANKL-mediated osteoclastogenesis, leading to the pathogenically augmented bone resorption in periradicular lesions. These data also suggest that the approach to neutralize MIF activity may lead to the development of a therapeutic regimen for the prevention of pathogenic bone loss in periradicular periodontitis.
RAS-RAF-MEK-ERK and PI3K-AKT pathways form a significant cascade for potential molecular target therapy in advanced cancer. The clinical significance of mutations in these genes in advanced gastric ...cancer (AGC) is uncertain.
We collected formalin-fixed, paraffin-embedded and fresh frozen tumor samples from AGC patients and analyzed the KRAS, NRAS, BRAF and PIK3CA mutations by direct-sequencing. We retrospectively investigated the clinicopathological features of these mutations in AGC patients, and selected patients with metastatic gastric cancer.
Among 167 AGC patients, mutations of KRAS codons 12/13 (N = 8/164, 4.9%), PIK3CA (N = 9/163, 5.5%), and NRAS codon 12/13(N = 3/159, 1.9%) were detected. Comparison of the clinicopathological features of the mutated KRAS, PIK3CA, NRAS genes with an all-wild type of these genes showed that the frequency of the intestinal type was significantly higher in patients whose tumor tissue contained KRAS mutations (P = 0.014). Among 125 patients with metastatic gastric cancer, patients with NRAS codon 12/13 mutations in their tumors had shorter overall survival compared with NRAS wild-type patients (MST: 14.7 vs 8.8 months, P = 0.011). By multivariate analyses, NRAS codon 12/13 mutation was an indicator for poor prognosis in patients with metastatic gastric cancer (adjusted HR 5.607, 95% CI: 1.637-19.203).
Our study indicated that mutations of KRAS, PIK3CA and NRAS were rare in AGC. NRAS mutations were likely to associate with poor prognosis in metastatic state of AGC patients, but further validation of other research is required.
Background
Previous studies have suggested an association between the use of direct‐acting antiviral agents (DAAs) for treating hepatitis C virus (HCV) infection and the resulting decrease in the ...incidence of hepatocellular carcinoma (HCC); however, it is unclear whether DAAs prevent the recurrence of HCC after curative treatment for HCC. This study aimed to prospectively investigate HCC recurrence and its predictors after curative treatment for HCC.
Methods
A total of 3012 patients with chronic HCV infection, with or without cirrhosis, who were treated with DAAs were enrolled between January 1, 2015 and January 31, 2017 as per the institutional review board approved study protocol at 15 institutions, including 10 university hospitals and five high‐volume centers in the Kyusyu area of Japan. Of the 3012 patients, 459 patients who had HCC but were cured with surgery or ablation therapy (curative treatment) before the use of DAAs were included in the analysis.
Results
During a mean follow‐up period of 29.4 months, 217 (47.2%) patients developed HCC recurrence. The median time to recurrence was 34.0 months, and the 1‐, 2‐, and 3‐year cumulative HCC recurrence rates were 27.1%, 43.4%, and 50.8%, respectively. The risk factors for HCC recurrence were the α‐fetoprotein (AFP) level before DAA therapy (P = 0.0047) and the number of curative treatments for HCC before DAA therapy (P < 0.0001).
Conclusions
A high AFP level and multiple occurrences of HCC before DAA therapy are associated with a high risk for HCC recurrence after curative treatment. Follow‐up after DAA therapy should include special attention to the abovementioned risk factors.
HCC recurred in 47.2% (217/459) of patients with precured HCV‐related HCC, who achieved SVR12 by DAA therapy, during a long mean follow‐up period of 29.4 months in this prospective study. High AFP level and multiple occurrences of HCC before DAA therapy were significant risk factors for the recurrence.
Abstract
Boron neutron capture therapy (BNCT) is an innovative cancer therapy that selectively destroys only cancer cells by utilizing the reaction between boron agents, which selectively accumulate ...in cancer cells, and neutron beams. However, the irradiation field in BNCT is a mixture of multiple radiation types, making accurate dose evaluation difficult. For dose evaluation in cancer tissue, which is particularly important, it is essential to discriminate between neutrons and
γ
-rays mixed in the BNCT irradiation field and to measure them correctly. In this paper, we introduce a new method for selective measurement of neutrons and
γ
-rays using a thermoluminescent phosphor, which is expected to be a promising method for improving the accuracy of dose evaluations.
Prognosis following recurrence subsequent to complete resection of non-small-cell lung cancer (NSCLC) is considered a multifactorial process dependent on clinicopathological, biological and treatment ...characteristics. Gefitinib was approved for lung cancer treatment in Japan in 2002. The aim of the current study was to quantify the prognostic effects of these characteristics on post-recurrence prognosis. In total, 127 NSCLC patients were analyzed who underwent complete resection and subsequently had recurrent cancer. The correlation between characteristics of the initial and recurrent disease with post-recurrence prognosis was investigated. The factors clearly associated with post-recurrence prognosis using Cox proportional hazards models were age at recurrence (those <65 years of age typically had better prognoses) and interval between initial resection and recurrence (intervals of <1 year accompanied a worse prognosis). Epidermal growth factor receptor (EGFR) mutant patients treated with EGFR tyrosine kinase inhibitors (TKIs), exhibited the longest median survival following recurrence (37.4 months) in the sample. Treatment, particularly EGFR TKIs for recurrent NSCLC, was observed to significantly prolong survival. The results of the study highlight that various treatment modalities according to the clinical background of the patient should be considered in patients with postoperative recurrent NSCLC.
Lettuce is one of the most suitable plant species to grow indoor or in a Plant Factory with Artificial lighting (PFAL) system, due to its short height and the relatively low light saturation point. ...Red lettuces are highly cultivated in PFALs, highly appreciated for its unique pigmentation and antioxidant activity, especially, the anthocyanin content that gives it the red color. However, red lettuces cultivated with PFAL in controlled environments face the challenge of having low anthocyanin content due of the lack of ultraviolet (UV) light that is necessary for its production. In this study, two red-lettuce cultivars ‘Annapolis’ and ‘Salanova’ were grown in a plant factory with LEDs (light-emitting diode) and UV light treatments to compare their growth trajectory and nutritional characteristics. Other characteristics such as Fresh Weight (FW) and total leaf area were measured to evaluate the influence of UV light in the lettuce growth. The nutritional quality of lettuces was assessed by measuring anthocyanins and polyphenols contents using a microplate reader and their ascorbic acid content measured via a reflectometer. Fresh Weight (FW), leaf area and leaf thickness under the conditions of this study, showed no effect (p>0.05) on the plants growth with the incorporation of UV radiation. However, the incorporation of UV light increased the functional components in ‘Annapolis’ and ‘Salanova’ lettuces. The polyphenol and anthocyanins contents in both lettuce cultivars showed significant differences (p<0.05). For ascorbic acid content, a significant difference was found only for ‘Annapolis’ lettuce. The incorporation of UV light can increase the functional ingredients such as polyphenols and anthocyanins without growth suppression for ‘Salanova’ cultivar. UV light increased polyphenol and anthocyanins contents in both cultivars, making them suitable cultivars for PFAL under the growth conditions used in this experiment. These results taken together can be used to improve the accumulation of functional ingredients in red lettuces without growth suppression incorporating UV light and that could be suitable for production in PFALs.
We focused on responses to grazing by individual species and functional groups in relation to ecological thresholds in Mongolian rangelands, with repeated measures from the same ecological sites to ...account for rainfall variability. At all sites, even under rainfall fluctuations, there were robust combinations of indicator species that could be used to forewarn managers to take action to minimize the probability of crossing ecological thresholds. Depending on the landscape condition of each site, the cover of functional groups, which shared traits of perennial life history, grass or forb growth form, linear leaf shape, and alternate leaf attachment, or the cover of functional groups of woody shrubs dramatically decreased before an ecological threshold was crossed. Thus, across all sites, the responses of certain functional groups to grazing appeared to predict the crossing of an ecological threshold. The ecological indicators derived in this study should help to improve land managers' ability to prevent adverse changes in states before ecological thresholds are reached.
Skin toxicity is a known clinical signature used to predict the prognosis of anti‐epidermal growth factor receptor (EGFR) antibody treatment in metastatic colorectal cancer (mCRC). There are no ...biological markers to predict skin toxicity before anti‐EGFR antibody treatment in mCRC patients. Between August 2008 and August 2011, pretreatment serum samples were obtained from KRAS wild‐type (WT) patients who received anti‐EGFR antibody treatment. Serum levels of ligands were measured by ELISA. A total of 103 KRAS WT patients were enrolled in the study. Progression‐free survival and overall survival of patients with a high grade (grade 2–3) of skin toxicity were significantly longer than those with a low grade (grade 0–1) of skin toxicity (median progression‐free survival, 6.4 months vs 2.4 months, P < 0.001; median overall survival, 14.6 months vs 7.1 months, P = 0.006). There were significant differences in distribution of serum levels of epiregulin (EREG), amphiregulin (AREG), and hepatocyte growth factor (HGF) between groups of low/high grade of skin toxicity (P < 0.048, P < 0.012, P < 0.012, respectively). In addition, serum levels of HGF, EREG, and AREG were inversely proportional to grades of skin toxicity as determined by the Cochran–Armitage test (P = 0.019, P = 0.047, P = 0.021, respectively). Our study indicated that serum levels such as HGF, EREG, and AREG may be significant markers to predict the grade of skin toxicity and the prognosis of anti‐EGFR antibody treatment, which contribute to improvement of the management of skin toxicity and survival time in mCRC patients.
We evaluated the associtation between serum levels of ligands and grade of skin toxicity by anti‐EGFR antibody treatment in metastatic clorectal cancer patients. Serum levels of HGF, EREG and AREG were inversely proportional to grades of skin toxicity as determined by the Cochran–Armitage test (P = 0.019, P = 0.047, P = 0.021, respectively). Our study indicated that serum levels such as HGF, EREG and AREG may be significant markers to predict the grade of skin toxicity and the prognosis of anti‐EGFR antibody treatment.
Postoperative swelling is a common complication of orthognathic surgery. The authors used three-dimensional (3D) image analysis and body surface temperature to determine the effects of compression ...taping (CT) and Kinesio taping (KT) by the epidermis, dermis, and fascia method (EDF-KT) on postoperative swelling.
The authors conducted a prospective, parallel-group, randomized controlled trial. Among the 162 patients diagnosed with jaw deformity and who underwent orthognathic surgery from August 2020 to October 2022, 105 patients (men: 36, women: 69, mean age: 28.27±8.92) underwent Le Fort type I + sagittal split ramus osteotomy (SSRO) or SSRO and were included in this study. Patients were randomly divided into three groups: EDF-KT group (
=31), CT group (
=41), and no tape group (control group,
=30). All taping was performed immediately postoperatively and removed on postoperative day (POD) 5. Three-dimensional images of the participants' faces were obtained preoperatively and at PODs 3, 7, 30, and 90 using a hand-held 3D imaging system and infrared thermography.
No significant difference was observed in postoperative swelling and postoperative body surface temperature between the groups at each time point. The CT group showed a trend towards reduced swelling on PODs 3 and 7 and a trend toward residual swelling on POD 90. The EDF-KT group showed a trend towards an increase in postoperative body surface temperature.
CT taping may not be appropriate for postoperative swelling control, suggesting that EDF-KT may affect body surface temperature. Further validation of the efficacy of KT for jaw deformities is needed.
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