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PDF file - 110K, Primer sequences for real-time PCR and RT-PCR

PDF file - 256K, Figure S1. Effects of aCXCL10 on tumor metastasis into lungs and adrenal glands. Figure S2. CXCL10-induced adhesion and survival of B16F10 cells

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This study aimed to examine the effectiveness of a discharge plan model for South Korean patients with cancer who had completed treatment and were returning to the community. Overall, 23 patients with cancer were recruited at the National Cancer Center in Goyang-si. The effectiveness of the discharge plan was examined using four methods: Social Needs Screening Toolkit (2018), early screening for discharge plan, current life situation v.2.0, and a questionnaire regarding problems after discharge from the hospital. Subsequently, the results were analyzed using descriptive statistical analysis methods with the Stata 14.0 program. The largest age group of study participants was between 45 and 64 years. No participants responded to urgent needs, whereas nine (39.13%) participants needed support for their social needs. According to the in-depth evaluation of participants, more than 80% of the respondents answered that patients with cancer needed no help in self-management, daily living activities, or mental health. The satisfaction survey results showed that the degree to which the “discharge plan” was helpful for health management at home after discharge was 4.41 of 5, and the degree to which it helped return to daily life was 3.86 of 5.

Background Mistletoe extract, used as a complementary chemotherapeutic agent for cancer patients, has anticancer effects against various malignancies. The aim of the present study was to evaluate the effect of mistletoe extract (Abnoba Viscum Q®) on tumor responses to neoadjuvant chemoradiotherapy (NCRT) for locally advanced rectal cancer. Methods This study included patients with rectal cancer who underwent NCRT between January 2018 and July 2020. In the mistletoe group (MG), the patients were administered Abnoba Viscum Q® subcutaneously during chemoradiotherapy—maintained just before surgery. Patient demographics, clinical outcomes, histopathological outcomes, and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL) assay results were compared between the MG and non-mistletoe group (NMG). Two rectal cancer cell lines (SNU-503 and SNU-503R80Gy) were treated with Abnoba Viscum Q® to assess its mechanistic effects in vivo. Results Overall, the study included 52 patients (MG: n = 15; NMG: n = 37). Baseline demographics between the two groups were similar, except carbohydrate antigen 19-9 levels and tumor location from the anal verge. There was no difference in the clinical stage between the two groups. A better tumor response in the MG, relative to the NMG, was observed with respect to tumor regression grade (TRG), T stage, and overall tumor–node–metastasis stage. Tumor response was significantly better in the MG than in the NMG in terms of pathologic complete response rate (53.3% vs. 21.6%, P = 0.044), good TRG response (66.7% vs. 32.4%, P = 0.024), T downstaging (86.7% vs. 43.2%, P = 0.004), and overall downstaging (86.7% vs. 56.8%, P = 0.040). The toxicities during NCRT were minimal in both groups. More apoptotic cells were noted in MG samples than in the NMG samples on TUNEL staining. Cleaved caspase-3 level following treatment with Abnoba Viscum Q® was higher in SNU-503R80Gy cells than in SNU-503 cells. Conclusion Patients treated with chemoradiation combined with mistletoe extract showed better outcomes than patients not treated with mistletoe extract in terms of tumor responses. This diversity in treatment may improve the efficacy of NCRT, leading to better oncologic outcomes. Prospective and randomized studies with long-term follow-up are warranted to confirm and extend these results.

The Asia-Pacific War clearly had a great social and psychological impact on Japanese women. Two additional types of female factory laborers who are the focus of this article—those hired under the J...

Background: Neoadjuvant chemoradiotherapy (nCRT) prior to surgery is considered standard therapy for locally advanced rectal cancer. Unfortunately, most patients with rectal cancer are resistant to radiotherapy. This might be a genetic cause. The role of certain rectal cancer-causing genes has not been completely elucidated. This study aims to investigate the genes responsible for locally advanced rectal cancer patients not reacting to radiotherapy. Methods: Whole exome sequencing of the DNA samples was performed on the samples. Bioinformatic analysis on the subjects was established. Individual genetic information was screened to identify differently expressed genes that more frequently appeared in non-complete response (NCR) compared to complete response (CR) patients after nCRT. All variations were verified by Sanger sequencing. Results: Genotyping information and pathway analyses of the samples indicated genes such as FLCN, CALML5, and ANTXR1 to be commonly mutated in CR group, whereas genes such as GALNTL14, CNKSR1, ACD, and CUL3 were more commonly mutated in the NCR group. Chi-square test revealed some significant variants (

Aberrant overactivation/overexpression of NRF2 is implicated as a driving event in tumor progression, which has been attributed to its mutation or inactivation of the inhibitory protein, KEAP1. However, alternative mechanisms responsible for sustained activation of NRF2 are less understood.Human colon cancer cell lines and tissues obtained from colorectal cancer (CRC) patients were used. To examine the expression levels of ARD1 and NRF2, Western blot and immunofluorescence analyses were performed. To investigate the potential relevance of NRF2 and ARD1 to human CRC, NRF2 and ARD1 were individually silenced in human colon cancer cells (HCT-116) by transfection with their specific small interfering RNA (siRNA). To determine the functional role of ARD1 in NRF2 regulation, in situ proximate ligation, co-immunoprecipitation, nano-LC-ESI MS/MS, and in vitro acetylation assays were performed.ARD1 knockdown in human colon cancer cell lines significantly reduced the protein levels of NRF2 without affecting its mRNA expression; however, silencing of NRF2 did not alter ARD1 protein expression. In addition, these two proteins were co-localized and physically interacted with each other both in human colon cancer cells (HCT-116) and human colon tumor tissues. Mechanistically, ARD1 overexpression increased the acetylation levels of NRF2. Moreover, an in vitro acetylation assay and mass spectrometric analysis demonstrated that ARD1 could directly acetylate NRF2. Ectopic expression of mutant forms of ARD1 with defective acetyltransferase activity reduced the stability of NRF2.In conclusion, ARD1 may potentiate the oncogenic function of NRF2 in human colon cancer by stabilizing this transcription factor.

Purpose We studied the effect of interleukin-8 (IL-8) as the factor for angiogenesis in the joint fluid of remnant-preserved anterior cruciate ligament reconstruction (RP-ACLR). Materials and methods We measured 12 cytokines in joint fluid by multiplex assay and assessed the relationship between IL-8 and vascular endothelial growth factor (VEGF) concentrations. The signal intensity and mean sagittal diameter via postoperative magnetic resonance imaging (MRI) scans were evaluated and the stress X-ray image was analyzed at 3, 6, and 12 months after operation. Results The IL-8 concentration was highest 3 months postoperatively in those patients who underwent RP-ACLR. Clinical data also showed that the signal intensity and stress radiography of the knee graft were significantly better at the early postoperative stage. Discussion Our results show that IL-8 plays an important role in angiogenesis within 3 months after RP-ACLR. This effect yields better recovery after operation. RP-ACLR patients with high knee stability in clinical data were identical to those with high expression of IL-8 in experimental data. Therefore, IL-8 has been shown to help revascularization and ligamentization of the grafted tendon. These results indicate that IL-8 in RP-ACLR is an important factor for angiogenesis after operation. Unfortunately, the relationship of IL-8 and VEGF in vivo has not been studied. Conclusion Our results showed that the IL-8 concentration was very high within 3 months after RP-ACLR operation. The increase in concentration of IL-8 over time was consistent with the increase in VEGF concentration. In the IL-8 clinical setting, MRI analysis showed that ACL synovialization and tension were better in patients who underwent the remnant preservation method. In addition, it was shown that RP-ACLR may be advantageous for early anterior stability within 1 year post operation and beneficial for tendon graft in the early stage post operation. Taken together, our findings suggest that IL-8 may contribute to angiogenesis which is helpful for revascularization and ligamentization of the graft tendon in the early stages of RP-ACLR.

The actual situation of domestic addicts is one in eight. Furthermore, addiction is making the next generation sick. The number of alcohol, drug,...

Sirtuin 1 (SIRT1), an NAD+ -dependent histone/protein deacetylase, has multifaceted functions in various biological events such as inflammation, aging and energy metabolism. The role of SIRT1 in carcinogenesis, however, is still under debate. Recent studies have indicated that aberrant overexpression of SIRT1 is correlated with metastasis and poor prognosis in several types of malignancy, including colorectal cancer. In the present study, we found that both SIRT1 and SIRT1 phosphorylated on serine 27 were coordinately upregulated in colon cancer patients' tissues and human colon cancer cell lines. This prompted us to investigate a biological role of phospho-SIRT1 in the context of colon cancer progression. Phosphorylation-defective mutant SIRT1, in which serine 27 was substituted by alanine (SIRT1-S27A), exhibited lower protein stability compared to that of wild-type SIRT1. Notably, human colon cancer (HCT-116) cells harbouring the SIRT1-S27A mutation showed decreased cell proliferation and reduced capability to form xenograft tumor in athymic nude mice, which was accompanied by diminished transcriptional activity of Snail. HCT-116 cells carrying SIRT1-S27A were less capable of deacetylating the Snail protein, with a concomitant decrease in the levels of interleukin (IL)-6 and IL-8 mRNA transcripts. Taken together, these observations suggest that SIRT1 stabilized through phosphorylation on serine 27 exerts oncogenic effects at least partly through deacetylation-dependent activation of Snail and subsequent transcription of IL-6 and IL-8 in human colon cancer cells.

Background Mistletoe extract, which is usually used as a complementary agent for cancer patients, provides an anticancer effect on various malignancies. The present study aimed to evaluate the effect of mistletoe extract (Abnoba Viscum Q®) on tumor responses in neoadjuvant chemoradiotherapy for locally advanced rectal cancer. Methods The rectal cancer patients who underwent neoadjuvant chemoradiotherapy were analyzed from Jan 2018 to Jul 2020. In the mistletoe group (MG), the patients were administered Abnoba Viscum Q® subcutaneously during chemoradiotherapy, and it was maintained just before surgery. Patients' demographics, clinical outcomes, and histopathological outcomes were compared between chemoradiation with the MG and nonmistletoe group (NMG). Results A total of 52 patients were included. There were MG of 15 patients and NMG of 37 patients. Baseline demographics were statistically similar between the two groups except the CA19-9 and tumor location levels from anal verge. There was no difference in the clinical stage for both groups. We also observed better tumor response in MG in terms of TRG, T stage, and overall TNM stage. Tumor response was significantly better in MG comparing NMG in terms of pathologic complete response rate (53.3% vs 21.6%, p = 0.044), good responder of tumor regression grade (66.7% vs 32.4%, p = 0.024), T downstaging (86.7% vs 43.2%, p = 0.004), and overall downstaging (86.7% vs 56.8%, p = 0.040). The toxicities during NCRT in both groups were minimal. Conclusion MG treated with chemoradiation combined with mistletoe extract showed better outcomes than NMG in terms of tumor responses. This diversity in treatment may elevate the method to hope for better oncologic outcomes. Prospective and randomized studies with long-term follow-up are warranted to confirm and extend this study.

We analyzed responsiveness of KRAS-mutated CRC cell lines with distinctive MSI status against mitogen-activated protein kinase (MEK) inhibitor (selumetinib; AZD) and/or B-raf proto-oncogene (BRAF) kinase inhibitor (vemurafenib; PLX). The viability of MSI-high (MSI-H) KRAS-mutated LS174T cells treated with AZD or PLX was 24.5 ± 0.9% or 71.4 ± 3.6%, respectively, and the viability of microsatellite stable (MSS) KRAS-mutated SW480 cells for AZD or PLX was 57.4 ± 3.1% or 43.1 ± 1.8%, respectively. These observations imply that the therapeutic efficacy of MEK kinase inhibitors or BRAF kinase inhibitors against KRAS-mutated colon cancer cells may differ between MSI-H and MSS. However, a combination of both inhibitors synergistically inhibits the proliferation of KRAS-mutated colon cancer cells regardless of MSI status. The underlying synergistic cytotoxic efficacy of AZD/PLX combination on KRAS-mutated colon cancer cells with different MSI status was further substantiated by markedly decreased phosphorylation of ERK in both LS74T and SW480 cell lines upon AZD and PLX treatment. Based on these collective data, we propose that MSI status should be considered when MEK kinase inhibitor or BRAF kinase inhibitor is treated for KRAS-mutated colon cancer, and that combination of both inhibitors synergistically inhibit proliferation of KRAS-mutated colon cancer cells independent of MSI status.

Background Leukocyte-poor platelet-rich plasma (LP-PRP) from peripheral blood is currently used as a concentrated source of growth factors to stimulate repair at sites of soft tissue injury. Fibroblasts are primary mediators of wound healing. Thus, we aimed to assess the positive effect of LP-PRP on human fibroblast proliferation in vitro. Methods LP-PRP was prepared from 49 donors. The fibroblasts were seeded, and at 24 hours after seeding, 1 × 107/10 µL LP-PRP was added once to each well. The cells were harvested 10 times during study period at our planned points, and we examined cell proliferation using the water-soluble tetrazolium salt-1 assay. We collected the supernatants and measured the amount of growth factors such as platelet-derived growth factor (PDGF)-AB/BB, insulin-like growth factor-1 (IGF-1), transforming growth factor-β1 (TGF-β1), and vascular endothelial growth factor (VEGF), which are known to be involved in wound healing processes, by multiplex assay. Results Human fibroblasts treated with LP-PRP showed a significant increase in proliferation when compared to untreated controls (p < 0.001 at days 4, 6, and 8). Multiplex cytokine assays revealed various secretion patterns. PDGF-AB/BB appeared at early time points and peaked before fibroblast proliferation. IGF-1 and TGF-β1 secretion gradually increased and peaked on days 4 and 6 post-treatment. The early VEGF concentration was lower than the concentration of other growth factors but increased along with cell proliferation. Conclusions Platelets in LP-PRP release growth factors such as PDGF, IGF-1, TGF-β1 and VEGF, and these growth factors have a promoting effect for human fibroblast proliferation, one of the important mediators of wound healing. These results suggest that growth factors derived from LP-PRP enhance the proliferation of human fibroblast.