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The present study was performed to determine the clinical relevance of KLF7 in tongue squamous cell carcinoma (TSCC) and to characterize its potential function and mechanism of action.
KLF7 expression was measured by RT-qPCR in 21 tongue cancer samples. The clinical relevance of KLF7 was analyzed in another cohort of 127 TSCC samples from a public database. Then, we performed RNA sequencing analysis in KLF7-overexpressing TSCC (SCC9 and CAL27) cells to define significantly altered pathways. The possible changes in migration and adhesion were then analyzed in KLF7-overexpressing and knockdown TSCC cells.
Our results showed that KLF7 mRNA expression was upregulated in TSCC and was significantly associated with the T and N stages. Patients with high-KLF7 expression had worse overall survival. RNA sequencing and KEGG enriched pathway analysis showed that altered genes were enriched in extracellular matrix-receptor interactions and focal adhesions in both cell lines. KLF7-overexpressing TSCC cell lines showed enhanced migration capacity and cell adhesion ability, and knockdown of KLF7 expression decreased TSCC migration and adhesion ability.
We concluded that KLF7 was overexpressed in TSCC and has prognostic value. KLF7 promoted TSCC migration and increased cell adhesion.
We concluded that KLF7 was overexpressed in TSCC and has prognostic value. KLF7 promoted TSCC migration and increased cell adhesion.Large increases in treatment of Common Mental Disorders (CMD) have failed to reduce population prevalence and global burden. Preventive strategies are needed to lower CMD prevalence and burden. Giving prevention a real chance to prove its promise will require (a) full embedment in social institutions; (b) long-term structural funding; (c) targeting major CMD determinants early in life combining population-level and individual-level strategies; and, (d) integrated evaluation of short-term and long-term effects to guide implementation. Targeting life skills and resilience of children and parenting skills of their parents has the potential for long-term benefits for multiple outcomes including well-being, social, economic, and financial domains as well as mental health outcomes. However, the large investments may not occur without compelling proof of effectiveness, but evaluation of effectiveness cannot occur without long-term, structural investments. Overcoming this impasse requires a paradigm shift. Randomized controlled trials of initial efficacy need to be supplemented by evaluation strategies for long-term surveillance of community-based programs that guide implementation while assessing long-term effectiveness.
Apatinib has potential as an effective and safe second-line or higher treatment for patients with chemotherapy-refractory esophageal squamous cell carcinoma (ESCC). EHT 1864 nmr Clinical safety is of potential concern when administering apatinib to patients with uncontrolled esophageal lesions or severe invasion of trachea, bronchi, or major blood vessels. To the best of the authors' knowledge, this is the first prospective phase II study to investigate apatinib for patients with chemotherapy-refractory ESCC. Apatinib could provide an alternative option for ESCC after first-line or higher therapy in carefully selected patients.
The aim of this study was to evaluate the efficacy and adverse effects of the oral vascular endothelial growth factor receptor 2 (VEGFR-2) tyrosine kinase inhibitor apatinib in patients with chemotherapy-refractory esophageal squamous cell carcinoma (ESCC).
We enrolled patients with chemotherapy-refractory ESCC. All patients received continuous apatinib 500 mg once daily.
Between July 2017 or patients with chemotherapy-refractory ESCC whose primary tumors are controlled and without severe invasion of trachea, bronchi, or major blood vessels.
Apatinib has potential as an effective and safe treatment for patients with chemotherapy-refractory ESCC whose primary tumors are controlled and without severe invasion of trachea, bronchi, or major blood vessels.Improved imaging and neoadjuvant chemotherapy (NAT) have led to higher pathologic complete response rates (pCR) in patients with invasive breast cancer. This has questioned the necessity of surgery and axillary lymph node (ALN) dissection in these patients. Prospective clinical trials are implementing extensive core biopsies of the tumor bed of patients with clinical complete response as a means to identify and spare them breast surgery. In addition, it is anticipated that patients with pCR are most likely going to have no or minimal disease in ALN as well. To verify the feasibility of these trials, we performed a pathologic analysis of all our patients who have undergone NAT from 2009 to present. Using pathology data base, we identified 362 patients treated with neoadjuvant chemotherapy followed by surgery. Clinical and pathologic information including gross and microscopic descriptions as well as biomarker status was collected. pCR was 50% for patients with negative ALN pretreatment but only 28% for patients with positive ALN at diagnosis. Despite achieving pCR in the breast, up to 10% of patients with positive ALN and 1% with negative ALN had persistent disease. Eight percent of patients that were presumed to have no ALN disease either clinically and or by imaging were found to have metastatic carcinoma in ALN. The metastases were predominantly (80%) less then 5 mm, and not palpable on physical examination and or due to biopsy sampling error. pCR in breast and ALN directly correlated with tumor size, ALN disease, and Her2 positive and triple negative receptor phenotype. In breast cancer patients who are node positive at time of diagnosis with pCR in the breast after neoadjuvant chemotherapy, residual lymph node disease was very uncommon. Further study is warranted to select patients who may avoid breast and axillary surgery post neoadjuvant chemotherapy.Secreted proteins are key players in fungal physiology and cell protection against external stressing agents and antifungals. Oak stress-induced protein 1 (OSIP1) is a fungal-specific protein with unknown function. By using Podospora anserina and Phanerochaete chrysosporium as models, we combined both in vivo functional approaches and biophysical characterization of OSIP1 recombinant protein. The P. anserina OSIP1Δ mutant showed an increased sensitivity to the antifungal caspofungin compared to the wild type. This correlated with the production of a weakened extracellular exopolysaccharide/protein matrix (ECM). Since the recombinant OSIP1 from P. chrysosporium self-assembled as fibers and was capable of gelation, it is likely that OSIP1 is linked to ECM formation that acts as a physical barrier preventing drug toxicity. Moreover, compared to the wild type, the OSIP1Δ mutant was more sensitive to oak extractives including chaotropic phenols and benzenes. It exhibited a strongly modified secretome pattern and an increased production of proteins associated to the cell-wall integrity signalling pathway, when grown on oak sawdust.
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