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  • 1
    In: Journal of Biomedical Science, Springer Science and Business Media LLC, Vol. 29, No. 1 ( 2022-12)
    Abstract: The development of drug resistance in oral squamous cell carcinoma (OSCC) that frequently leads to recurrence and metastasis after initial treatment remains an unresolved challenge. Presence of cancer stem cells (CSCs) has been increasingly reported to be a critical contributing factor in drug resistance, tumor recurrence and metastasis. Thus, unveiling of mechanisms regulating CSCs and potential targets for developing their inhibitors will be instrumental for improving OSCC therapy. Methods siRNA, shRNA and miRNA that specifically target keratin 17 (KRT17) were used for modulation of gene expression and functional analyses. Sphere-formation and invasion/migration assays were utilized to assess cancer cell stemness and epithelial mesenchymal transition (EMT) properties, respectively. Duolink proximity ligation assay (PLA) was used to examine molecular proximity between KRT17 and plectin, which is a large protein that binds cytoskeleton components. Cell proliferation assay was employed to evaluate growth rates and viability of oral cancer cells treated with cisplatin, carboplatin or dasatinib. Xenograft mouse tumor model was used to evaluate the effect of KRT17- knockdown in OSCC cells on tumor growth and drug sensitization. Results Significantly elevated expression of KRT17 in highly invasive OSCC cell lines and advanced tumor specimens were observed and high KRT17 expression was correlated with poor overall survival. KRT17 gene silencing in OSCC cells attenuated their stemness properties including markedly reduced sphere forming ability and expression of stemness and EMT markers. We identified a novel signaling cascade orchestrated by KRT17 where its association with plectin resulted in activation of integrin β4/α6, increased phosphorylation of FAK, Src and ERK, as well as stabilization and nuclear translocation of β-catenin. The activation of this signaling cascade was correlated with enhanced OSCC cancer stemness and elevated expression of CD44 and epidermal growth factor receptor (EGFR). We identified and demonstrated KRT17 to be a direct target of miRNA-485-5p. Ectopic expression of miRNA-485-5p inhibited OSCC sphere formation and caused sensitization of cancer cells towards cisplatin and carboplatin, which could be significantly rescued by KRT17 overexpression. Dasatinib treatment that inhibited KRT17-mediated Src activation also resulted in OSCC drug sensitization. In OSCC xenograft mouse model, KRT17 knockdown significantly inhibited tumor growth, and combinatorial treatment with cisplatin elicited a greater tumor inhibitory effect. Consistently, markedly reduced levels of integrin β4, active β-catenin, CD44 and EGFR were observed in the tumors induced by KRT17 knockdown OSCC cells. Conclusions A novel miRNA-485-5p/KRT17/integrin/FAK/Src/ERK/β-catenin signaling pathway is unveiled to modulate OSCC cancer stemness and drug resistance to the common first-line chemotherapeutics. This provides a potential new therapeutic strategy to inhibit OSCC stem cells and counter chemoresistance.
    Type of Medium: Online Resource
    ISSN: 1423-0127
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 1482918-6
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  • 2
    In: Gastroenterology Research and Practice, Hindawi Limited, Vol. 2012 ( 2012), p. 1-7
    Abstract: Background and Study Aims . The optimal dose of intravenous proton-pump inhibitor (PPI) therapy for the prevention of peptic ulcer (PU) rebleeding remains controversial. This study aimed to understand the real world experiences in prescribing high-dose PPI and non-high-dose PPI for preventing rebleeding after endoscopic treatment of high-risk PU. Patients and Methods . A total of 220 subjects who received high-dose and non-high-dose pantoprazole for confirmed acute PU bleeding that were successfully treated endoscopically were enrolled. They were divided into rebleeding ( n = 177 ) and non-rebleeding groups ( n = 43 ). Randomized matching of the treatment-control group was performed. Patients were randomly selected for non-high-dose and high-dose PPI groups ( n = 44 in each group). Results . Univariate analysis showed, significant variables related to rebleeding were female, higher creatinine levels, and higher Rockall scores (≧6). Before case-control matching, the high-dose PPI group had higher creatinine level, higher percentage of shock at presentation, and higher Rockall scores. After randomized treatment-control matching, no statistical differences were observed for rebleeding rates between the high-dose and non-high-dose groups after case-control matching. Conclusion . This study suggests that intravenous high-dose pantoprazole may not be superior to non-high-dose regimen in reducing rebleeding in high-risk peptic ulcer bleeding after successful endoscopic therapy.
    Type of Medium: Online Resource
    ISSN: 1687-6121 , 1687-630X
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2012
    detail.hit.zdb_id: 2435460-0
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  • 3
    In: Oncogene, Springer Science and Business Media LLC, Vol. 37, No. 30 ( 2018-7), p. 4137-4150
    Type of Medium: Online Resource
    ISSN: 0950-9232 , 1476-5594
    RVK:
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2018
    detail.hit.zdb_id: 2008404-3
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  • 4
    In: BioMed Research International, Hindawi Limited, Vol. 2015 ( 2015), p. 1-6
    Abstract: Background . Foreign object ingestion and food bolus impaction are a common clinical problem. We report our clinical experiences in endoscopic management for adults, foreign body ingestion, and food bolus impaction. Method . A retrospective chart review study was conducted on adult patients with foreign body ingestion and food bolus impaction between January 2011 and November 2014. Patients with incomplete medical records were excluded. Results . A total of 198 patients (226 incidents) were included in the study (male/female: 1.54/1; age 57 ± 16 years). Among them, 168 foreign bodies were found successfully (74.3%). 75.6% of the foreign bodies were located in the esophagus. Food bolus impaction was most common (41.6%). 93.5% of foreign bodies in current study cohort were successfully extracted and 5 patients required surgical interventions. Comparisons between symptomatic and asymptomatic patients revealed that locations of foreign bodies in the pharynx and esophagus were the significant relevant factors ( P 〈 0.001 ). Shorter time taken to initiate endoscopic interventions increased detection rate (289.75 ± 465.94 versus 471.06 ± 659.93 minutes, P = 0.028 ). Conclusion . Endoscopic management is a safe and highly effective procedure in extracting foreign body ingestion and food bolus impaction. Prompt endoscopic interventions can increase the chance of successful foreign bodies’ detection.
    Type of Medium: Online Resource
    ISSN: 2314-6133 , 2314-6141
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2015
    detail.hit.zdb_id: 2698540-8
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  • 5
    In: PLOS ONE, Public Library of Science (PLoS), Vol. 17, No. 4 ( 2022-4-20), p. e0266876-
    Abstract: Norovirus (NoV) infection is common in pediatric patients with immunodeficiency and is more likely to cause severe disease. Objective Our study aims to figure out the clinical differences and distribution of intestinal microbiota in immunocompromised children with NoV gastroenteritis. Methods Pediatric patients admitted to Shang-Ho Hospital with diagnosis of acute gastroenteritis including different immune status were enrolled and their medical records were reviewed. NoV gastroenteritis was validated using RT-PCR molecular methods. Viral shedding period was determined by real-time RT-PCR assays. Intestinal microbiota enrichment analysis was carried out by next generation sequencing after fecal DNA extraction and subsequent Linear Discriminant Analysis (LDA) Effect Size (LEfSe) method. Results Significantly higher frequency of diarrhea [mean, (IQR), 3.8 (3–5) /day] and longer viral shedding time [mean, IQR, 8.5 (5–13) days] was found in immunocompromised NoV infections than in immunocompetent patients without NoV infections (p = 0.013*) and immunocompetent patients with NoV infections (p = 0.030**). The fever prevalence was significantly lower in immunocompromised NoV infections than in different immune or infection status. Intestinal microbiota metagenomics analysis showed no significant community richness difference while the LEfSe analysis showed a significant difference in commensal richness at the phylum level, the family level, and the genus level in patients under different immune status. Conclusion We evaluated the clinical significances and microbiota composition in immunocompromised children with norovirus gastroenteritis. This will further facilitate studies of the interaction between the intestinal microbiota in such patients with precise determination of their bacterial infection control and probiotic supplements strategy.
    Type of Medium: Online Resource
    ISSN: 1932-6203
    Language: English
    Publisher: Public Library of Science (PLoS)
    Publication Date: 2022
    detail.hit.zdb_id: 2267670-3
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  • 6
    In: Journal of Biomedical Science, Springer Science and Business Media LLC, Vol. 30, No. 1 ( 2023-07-12)
    Type of Medium: Online Resource
    ISSN: 1423-0127
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 1482918-6
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  • 7
    In: Journal of Biomedical Science, Springer Science and Business Media LLC, Vol. 29, No. 1 ( 2022-12-22)
    Abstract: Ovarian cancer has the highest mortality among gynecological cancers due to late diagnosis and lack of effective targeted therapy. Although the study of interplay between cancer cells with their microenvironment is emerging, how ovarian cancer triggers signaling that coordinates with immune cells to promote metastasis is still elusive. Methods Microarray and bioinformatics analysis of low and highly invasive ovarian cancer cell lines were used to reveal periostin (POSTN), a matrix protein with multifunctions in cancer, with elevated expression in the highly invasive cells. Anchorage independent assay, Western blot, RNA interference, confocal analysis and neutralizing antibody treatment were performed to analyze the effects of POSTN on tumor promotion and to explore the underlying mechanism. Chemotaxis, flow cytometry and cytokine array analyses were undertaken to analyze the involvement of POSTN in cancer-associated fibroblast (CAF) and macrophage modulation. Correlations between POSTN expression levels and clinical characteristics were analyzed using the Oncomine, commercial ovarian cancer cDNA and China Medical University Hospital patient cohort. In vivo effect of POSTN on metastasis was studied using a mouse xenograft model. Results Expression of POSTN was found to be elevated in highly invasive ovarian cancer cells. We observed that POSTN was co-localized with integrin β3 and integrin β5, which was important for POSTN-mediated activation of ERK and NF-κB. Ectopic expression of POSTN enhanced whereas knockdown of POSTN decreased cancer cell migration and invasion in vitro, as well as tumor growth and metastasis in vivo. POSTN enhanced integrin/ERK/NF-κB signaling through an autocrine effect on cancer cells to produce macrophage attracting and mobilizing cytokines including MIP-1β, MCP-1, TNFα and RANTES resulting in increased chemotaxis of THP-1 monocytes and their polarization to M2 macrophages in vitro. In agreement, tumors derived from POSTN-overexpressing SKOV3 harbored more tumor-associated macrophages than the control tumors. POSTN induced TGF-β2 expression from ovarian cancer cells to promote activation of adipose-derived stromal cells to become CAF-like cells expressing alpha smooth muscle actin and fibroblast activation protein alpha. Consistently, increased CAFs were observed in POSTN overexpressing SKOV3 cells-derived metastatic tumors. In clinical relevance, we found that expression of POSTN was positively correlated with advanced-stage diseases and poor overall survival of patients. Conclusions Our study revealed a POSTN-integrin-NF-κB-mediated signaling and its involvement in enhancing M2 macrophages and CAFs, which could potentially participate in promoting tumor growth. Our results suggest that POSTN could be a useful prognosis marker and potential therapeutic target.
    Type of Medium: Online Resource
    ISSN: 1423-0127
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 1482918-6
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  • 8
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2021
    In:  Cell Death & Disease Vol. 12, No. 12 ( 2021-11-17)
    In: Cell Death & Disease, Springer Science and Business Media LLC, Vol. 12, No. 12 ( 2021-11-17)
    Abstract: Certain immune cells and inflammatory cytokines are essential components in the tumor microenvironment to promote breast cancer progression. To identify key immune players in the tumor microenvironment, we applied highly invasive MDA-MB-231 breast cancer cell lines to co-culture with human monocyte THP-1 cells and identified CXCL7 by cytokine array as one of the increasingly secreted cytokines by THP-1 cells. Further investigations indicated that upon co-culturing, breast cancer cells secreted CSF1 to induce expression and release of CXCL7 from monocytes, which in turn acted on cancer cells to promote FAK activation, MMP13 expression, migration, and invasion. In a xenograft mouse model, administration of CXCL7 antibodies significantly reduced abundance of M2 macrophages in tumor microenvironment, as well as decreased tumor growth and distant metastasis. Clinical investigation further suggested that high CXCL7 expression is correlated with breast cancer progression and poor overall survival of patients. Overall, our study unveils an important immune cytokine, CXCL7, which is secreted by tumor infiltrating monocytes, to stimulate cancer cell migration, invasion, and metastasis, contributing to the promotion of breast cancer progression.
    Type of Medium: Online Resource
    ISSN: 2041-4889
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2541626-1
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  • 9
    In: Vaccines, MDPI AG, Vol. 11, No. 5 ( 2023-04-27), p. 905-
    Abstract: Coronaviruses can cause pneumonia, with clinical symptoms that may be similar to the symptoms of other viral pneumonias. To our knowledge, there have been no reports regarding cases of pneumonia caused by coronaviruses and other viruses among hospitalized patients in the past 3 years before and during coronavirus disease 2019 (COVID-19). Here, we analysed the causes of viral pneumonia among hospitalized patients during the coronavirus disease 2019 (COVID-19) pandemic (2019–2021). Between September 2019 and April 2021, patients hospitalized at Shuang Ho Hospital in north Taiwan with a diagnosis of pneumonia were enrolled in this study. Age, sex, onset date, and season of occurrence were recorded. Respiratory tract pathogens were identified with molecular detection using the FilmArray® platform from nasopharyngeal swabs. In total, 1147 patients (128 patients aged 〈 18 years and 1019 patients aged ≥18 years) with pneumonia and identified respiratory tract pathogens were assessed. Among the 128 children with pneumonia, the dominant viral respiratory pathogen was rhinovirus (24.2%), followed by respiratory syncytial virus (RSV; 22.7%), parainfluenza virus (1 + 2 + 3 + 4) (17.2%), adenovirus (12.5%), metapneumovirus (9.4%), coronavirus (1.6%), and influenza virus (A + B) (1.6%). Among the 1019 adults with pneumonia, the dominant viral respiratory pathogen was rhinovirus (5.0%), followed by RSV (2.0%), coronavirus (2.0%), metapneumovirus (1.5%), parainfluenza virus (1 + 2 + 3 + 4) (1.1%), adenovirus (0.7%), and influenza virus (A + B) (0%). From 2019–2021, older patients (aged 〉 65 years) with pneumonia tested positive for coronavirus most commonly in autumn. Coronavirus was not detected during summer in children or adults. Among children aged 0–6 years, RSV was the most common viral pathogen, and RSV infection occurred most often in autumn. Metapneumovirus infection occurred most often in spring in both children and adults. In contrast, influenza virus was not detected in patients with pneumonia in any season among children or adults from January 2020 to April 2021. Among all patients with pneumonia, the most common viral pathogens were rhinovirus in spring, adenovirus and rhinovirus in summer, RSV and rhinovirus in autumn, and parainfluenza virus in winter. Among children aged 0–6 years, RSV, rhinovirus, and adenovirus were detected in all seasons during the study period. In conclusion, the proportion of pneumonia cases caused by a viral pathogen was higher in children than the proportion in adults. The COVID-19 pandemic period evoked a need for SARS-CoV-2 (severe acute respiratory disease coronavirus 2) vaccination to prevent the severe complications of COVID-19. However, other viruses were also found. Vaccines for influenza were clinically applied. Active vaccines for other viral pathogens such as RSV, rhinovirus, metapneuomoccus, parainfluenza, and adenovirus may need to be developed for special groups in the future.
    Type of Medium: Online Resource
    ISSN: 2076-393X
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2703319-3
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  • 10
    Online Resource
    Online Resource
    Japan Society of Histochemistry & Cytochemistry ; 2000
    In:  ACTA HISTOCHEMICA ET CYTOCHEMICA Vol. 33, No. 5 ( 2000), p. 367-375
    In: ACTA HISTOCHEMICA ET CYTOCHEMICA, Japan Society of Histochemistry & Cytochemistry, Vol. 33, No. 5 ( 2000), p. 367-375
    Type of Medium: Online Resource
    ISSN: 0044-5991 , 1347-5800
    Language: English
    Publisher: Japan Society of Histochemistry & Cytochemistry
    Publication Date: 2000
    detail.hit.zdb_id: 2106630-9
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