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  • 1
    Online Resource
    Online Resource
    Accelerated Wound Healing and Keratinocyte Proliferation through PI3K/Akt/pS6 and VEGFR2 Signaling by Topical Use of Pleural Fluid
    MDPI AG ; 2022
    In:  Cells Vol. 11, No. 5 ( 2022-02-26), p. 817-
    Details
    In: Cells, MDPI AG, Vol. 11, No. 5 ( 2022-02-26), p. 817-
    Abstract: Impaired wound healing is an ongoing issue that cancer patients undergoing chemotherapy or radiotherapy face. Our previous study regarding lung-cancer-associated pleural fluid (LCPF) demonstrated its propensity to promote endothelial proliferation, migration, and angiogenesis, which are crucial features during cutaneous wound healing. Therefore, the current study aimed to investigate the effect of pleural fluid on cutaneous wound closure in vitro and in vivo using HaCaT keratinocytes and a full-thickness skin wound model, respectively. Both heart-failure-associated pleural fluid (HFPF) and LCPF were sequentially centrifuged and filtered to obtain a cell-free status. Treatment with HFPF and LCPF homogeneously induced HaCaT proliferation with cell cycle progression, migration, and MMP2 upregulation. Western blotting revealed increased PI3K/Akt phosphorylation and VEGFR2/VEGFA expression in HaCaT cells. When treated with the PI3K inhibitor, LCPF-induced keratinocyte proliferation was attenuated with decreased pS6 levels. By applying the VEGFR2 inhibitor, LCPF-induced keratinocyte proliferation was ameliorated by pS6 and MMP2 downregulation. The effect of LCPF-induced cell junction rearrangement was disrupted by co-treatment with a VEGFR2 inhibitor. Compared with a 0.9% saline dressing, LCPF significantly accelerated wound closure and re-epithelization when used as a dressing material in a full-thickness wound model. Histological analysis revealed increased neo-epidermis thickness and dermis collagen synthesis in the LCPF-treated group. Furthermore, LCPF treatment activated basal keratinocytes at the wound edge with the upregulation of Ki-67, VEGFA, and MMP2. Our preliminaries provided the benefit of wet dressing with pleural fluid to improve cutaneous wound closure through enhanced re-epithelization and disclosed future autologous application in cancer wound treatment.
    Type of Medium: Online Resource
    ISSN: 2073-4409
    URL: Article
    DOI: 10.3390/cells11050817
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2661518-6
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  • 2
    Online Resource
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    Cervical Spine Metastasis as a Primary Manifestation of Occult Colorectal Carcinoma: Case Report
    S. Karger AG ; 2006
    In:  Visceral Medicine Vol. 22, No. 1 ( 2006), p. 58-60
    Details
    In: Visceral Medicine, S. Karger AG, Vol. 22, No. 1 ( 2006), p. 58-60
    Type of Medium: Online Resource
    ISSN: 2297-4725 , 2297-475X
    URL: Article
    DOI: 10.1159/000090805
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2006
    detail.hit.zdb_id: 2850734-4
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  • 3
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    Guggulsterone inhibits migration and invasion through proteasomal and lysosomal degradation in human glioblastoma cells
    Elsevier BV ; 2023
    In:  European Journal of Pharmacology Vol. 938 ( 2023-01), p. 175411-
    Details
    In: European Journal of Pharmacology, Elsevier BV, Vol. 938 ( 2023-01), p. 175411-
    Type of Medium: Online Resource
    ISSN: 0014-2999
    URL: Article
    DOI: 10.1016/j.ejphar.2022.175411
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
    detail.hit.zdb_id: 1483526-5
    SSG: 15,3
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  • 4
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    Survival Benefit of Statin with Anti-Angiogenesis Efficacy in Lung Cancer-Associated Pleural Fluid through FXR Modulation
    MDPI AG ; 2022
    In:  Cancers Vol. 14, No. 11 ( 2022-06-02), p. 2765-
    Details
    In: Cancers, MDPI AG, Vol. 14, No. 11 ( 2022-06-02), p. 2765-
    Abstract: Lung cancer-related pleural fluid (LCPF) presents as a common complication with limited treatment. Beyond its function in lipid digestion, bile acid was identified as a potent carcinogen to stimulate tumor proliferation. Previous research indicated a correlation between serum bile acid levels and the risk of developing several gastrointestinal cancers. Our study identified elevated bile acid levels in LCPF and increased farnesoid X receptor (FXR) expression as bile acid nuclear receptors in pleural microvessels of lung adenocarcinoma. Additionally, LCPF stimulated the expression of proteins involved in bile acid synthesis and cholesterol metabolism in HUVECs including CYP7A1, StAR, HMGCR, and SREBP2. LCPF-induced endothelial motility and angiogenesis were counteracted by using β-muricholic acid as an FXR antagonist. Moreover, we investigated the efficacy of cholesterol-lowering medications, such as cholestyramine, fenofibrate, and atorvastatin, in regulating LCPF-regulated angiogenesis. Along with suppressing endothelial proliferation and angiogenesis, atorvastatin treatment reversed cholesterol accumulation and endothelial junction disruption caused by LCPF. Statin treatment inhibited LCPF-induced endothelial FXR expression as well as the downstream proteins RXR and SHP. Based on the positive findings of suppressing endothelial angiogenesis, our group further incorporated the effect of statin on clinical patients complicated with LCPF. A Kaplan–Meier analysis revealed the clinical benefit of statin exposure in patients with lung adenocarcinoma with LCPF. Conclusively, our study demonstrated the ability of statin to alleviate LCPF-induced angiogenesis in patients with LCPF via FXR modulation.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers14112765
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527080-1
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  • 5
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    Hepatic cystic metastatic tumors from a locally controlled nasopharyngeal carcinoma
    Wiley ; 2016
    In:  Advances in Digestive Medicine Vol. 3, No. 2 ( 2016-06), p. 69-72
    Details
    In: Advances in Digestive Medicine, Wiley, Vol. 3, No. 2 ( 2016-06), p. 69-72
    Abstract: Liver cystic neoplasms are uncommon and vary from benign to overtly malignant. Liver cystic metastases are rare and mostly come from colon, pancreas, ovary, kidney, neuroendocrine, and prostate cancer. Nasopharyngeal carcinoma (NPC) with liver cystic metastasis has only been reported once. Here, we report a 52‐year‐old man with liver cystic metastasis from locally cured NPC. The patient received concurrent chemoradiotherapy for NPC 4 years ago and presented with a 6‐month history of upper abdominal fullness and pain. No evidence of local recurrence of NPC was found at his regular follow‐up examinations after concurrent chemoradiotherapy. Abdominal magnetic resonance imaging showed a large, well‐defined, lobulated cystic lesion with poor contrast enhancement occupying both lobes of the liver. Hepatic cystic metastasis was suspected. Ultrasound‐guided liver tumor biopsy was performed. Histological examinations disclosed a pattern of poorly differentiated squamous cell carcinoma with focal sarcomatoid differentiation based on the P40 immunohistochemical stain. In situ hybridization for Epstein–Barr virus early RNAs confirmed the diagnosis of metastatic NPC. It is difficult to make a diagnosis in liver cystic neoplasms, especially from a rarely reported origin. In our case, we used clinical history and Epstein–Barr virus early RNAs as a specific marker to make an accurate diagnosis.
    Type of Medium: Online Resource
    ISSN: 2351-9797 , 2351-9800
    URL: Article
    DOI: 10.1016/j.aidm.2014.09.001
    Language: English
    Publisher: Wiley
    Publication Date: 2016
    detail.hit.zdb_id: 2830898-0
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  • 6
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    High-Grade B-Cell Lymphoma (HGBL) with MYC and BCL2 and/or BCL6 Rearrangements Is Predominantly BCL6-Rearranged and BCL6-Expressing in Taiwan
    MDPI AG ; 2021
    In:  Cancers Vol. 13, No. 7 ( 2021-03-31), p. 1620-
    Details
    In: Cancers, MDPI AG, Vol. 13, No. 7 ( 2021-03-31), p. 1620-
    Abstract: This study investigated the epidemiological and clinical peculiarities of BCL2 and BCL6 rearrangement in patients with high grade B-cell lymphoma (HGBL) from Taiwan, compared with data from Western countries. Two hundred and eighty-two DLBCL cases from Taipei Medical University-affiliated hospitals (n = 179) and Tri-Service General Hospital (n = 103) were enrolled for this study. From the 282, 47 (16.7%) had MYC translocation; 24 of these harbored concurrent BCL2 and/or BCL6 translocation (double-hit, DH or triple-hit, TH). Twelve DH-HGBL cases had simultaneous MYC and BCL6 translocations, 8 harbored MYC and BCL2 rearrangement, while the remaining 4 patients exhibited TH. Together, 66.7% of DH/TH-HGBL patients were BCL6 rearrangement positive. Among these BCL6-rearranged DH/TH-HGBL patients, only 6 (37.5%) overexpressed MYC and BCL6 proteins simultaneously, indicating that MYC-BCL6 co-overexpression may not be plausible surrogate biomarker for screening BCL6-rearranged DH-HGBL. By the end of year 5, all patients with TH-HGBL, BCL2 DH-HGBL and all but one BCL6 DH-HGBL cases had expired or were lost to follow-up. Progression-free survival (PFS) was longer for the non-DH/TH-HGBL group compared with the DH/TH-HGBL group. While the patients with BCL2 DH-HGBL were lost to follow-up by day 800, their remaining TH-HGBL and BCL6 DH-HGBL peers exhibited very poor PFS, regardless of age strata. More so, patients with BCL6 rearrangement were 5.5-fold more likely associated with extranodal involvement compared with their BCL2-rearranged peers. Moreover, ~60.0% of the BCL6-rearranged DH-HGBL cases were non-GCB, suggesting that including screening for BCL6 rearrangement in patients with the non-GCB phenotype may aid medical decision-making and therapeutic strategy. Contrary to contemporary data from western countries, 2 in every 3 patients with DH/TH-HGBL in Taiwan harbor BCL6 rearrangement. Consistent with present findings, we recommend mandatory screening for BCL6 rearrangement in patients with aggressive HGBL in Taiwan.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers13071620
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2527080-1
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  • 7
    Online Resource
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    Effect of malignant‐associated pleural effusion on endothelial viability, motility and angiogenesis in lung cancer
    Wiley ; 2020
    In:  Cancer Science Vol. 111, No. 10 ( 2020-10), p. 3747-3758
    Details
    In: Cancer Science, Wiley, Vol. 111, No. 10 ( 2020-10), p. 3747-3758
    Abstract: Malignant pleural effusion (MPE) and paramalignant pleural effusion (PPE) remain debilitating complications in lung cancer patients with poor prognosis and limited treatment options. The role of vascular endothelial cells has not been explored in the pleural environment of lung cancer. By integrating MPE and PPE as malignant‐associated pleural fluid (MAPF), the current study aimed to evaluate the effect of MAPF on cell proliferation, migration and angiogenesis of HUVEC. First, increased capillaries were identified in the subpleural layer of lung adenocarcinoma. Compatible with pathological observations, the ubiquitous elevation of HUVEC survival was identified in MAPF culture regardless of the underlying cancer type, the driver gene mutation, prior treatments and evidence of malignant cells in pleural fluid. Moreover, MAPF enhanced HUVEC motility with the formation of lamellipodia and filopodia and focal adhesion complex. Tube formation assay revealed angiogenic behavior with the observation of sheet‐like structures. HUVEC cultured with MAPF resulted in a significant increase in MAPK phosphorylation. Accompanied with VEGFR2 upregulation in MAPF culture, there was increased expressions of p‐STAT3, HIF‐1α and Nf‐kB. VEGF/VEGFR2 blockade regressed endothelial migration and angiogenesis but not cell proliferation. Our data indicate the angiogenic activities of MAPF on vascular endothelial cells that revealed increased pleural capillaries in lung cancer. Targeting the VEGF/VEGFR2 pathway might modulate the angiogenic propensity of MAPF in future clinical investigations.
    Type of Medium: Online Resource
    ISSN: 1347-9032 , 1349-7006
    URL: Issue
    URL: Article
    DOI: 10.1111/cas.v111.10
    DOI: 10.1111/cas.14584
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2115647-5
    detail.hit.zdb_id: 2111204-6
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  • 8
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    Distinct JNK/VEGFR signaling on angiogenesis of breast cancer‐associated pleural fluid based on hormone receptor status
    Wiley ; 2021
    In:  Cancer Science Vol. 112, No. 2 ( 2021-02), p. 781-791
    Details
    In: Cancer Science, Wiley, Vol. 112, No. 2 ( 2021-02), p. 781-791
    Abstract: Malignant pleural effusion is a common complication in metastatic breast cancer (MBC); however, changes in the pleural microenvironment are poorly characterized, especially with respect to estrogen receptor status. Histologically, MBC presents with increased microvessels beneath the parietal and visceral pleura, indicating generalized angiogenic activity. Breast cancer‐associated pleural fluid (BAPF) was collected and cultured with HUVECs to recapitulate the molecular changes in subpleural endothelial cells. The clinical progression of triple‐negative breast cancer (TNBC) is much more aggressive than that of hormone receptor‐positive breast cancer (HPBC). However, BAPF from HPBC (BAPF‐HP) and TNBC (BAPF‐TN) homogeneously induced endothelial proliferation, migration, and angiogenesis. In addition, BAPF elicited negligible changes in the protein marker of endothelial‐mesenchymal transition. Both BAPF‐HP and BAPF‐TN exclusively upregulated JNK signaling among all MAPKs in HUVECs. By contrast, the response to the JNK inhibitor was insignificant in Transwell and tube formation assays of the HUVECs cultured with BAPF‐TN. The distinct contribution of p‐JNK to endothelial angiogenesis was consequently thought to be induced by BAPF‐HP and BAPF‐TN. Due to increased angiogenic factors in HUVECs cultured with BAPF, vascular endothelial growth factor receptor 2 (VEGFR2) inhibitor was applied accordingly. Responses to VEGFR2 blockade were observed in both BAPF‐HP and BAPF‐TN concerning endothelial migration and angiogenesis. In conclusion, the above results revealed microvessel formation in the pleura of MBC and the underlying activation of p‐JNK/VEGFR2 signaling. Distinct responses to blocking p‐JNK and VEGFR2 in HUVECs cultured with BAPF‐HP or BAPF‐TN could lay the groundwork for future investigations in treating MBC based on hormone receptor status.
    Type of Medium: Online Resource
    ISSN: 1347-9032 , 1349-7006
    URL: Issue
    URL: Article
    DOI: 10.1111/cas.v112.2
    DOI: 10.1111/cas.14772
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2115647-5
    detail.hit.zdb_id: 2111204-6
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  • 9
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    Concurrent Blockade of Endothelial EGFR and VEGF Signaling on Malignant Associated Pleural Fluid Induced Angiogenesis: From Clinic to Bench
    MDPI AG ; 2021
    In:  Biomedicines Vol. 9, No. 10 ( 2021-09-26), p. 1327-
    Details
    In: Biomedicines, MDPI AG, Vol. 9, No. 10 ( 2021-09-26), p. 1327-
    Abstract: Malignant-associated pleural fluid (MAPF) represented an unsolved problem in advanced lung cancer. Our previous work characterized increased pleural angiogenesis in lung adenocarcinoma and the propensity of MAPF on endothelial angiogenesis. This study investigated the combined efficacy of the tyrosine kinase inhibitor (gefitinib) and bevacizumab in opposing MAPF-induced angiogenesis. In lung adenocarcinoma patients with malignant pleural effusion (MPE), Kaplan–Meier analysis revealed the benefit of cotreatment with target therapy and bevacizumab. Increased EGFR expression was observed in the pleural microvessels of patients with lung adenocarcinoma both with and without mutations in EGFR. MAPF was obtained from lung adenocarcinoma patients both wild-type and mutant EGFRs. Total and phosphorylated EGFR were upregulated in HUVEC cultured with MAPF. Treatment with gefitinib as an EGFR inhibitor suppressed MAPF-induced endothelial migration and partially attenuated endothelial proliferation in both wild-type and mutant EGFR lung adenocarcinoma. Cotreatment with gefitinib and bevacizumab produced better inhibition of MAPF-induced endothelial angiogenesis than gefitinib alone in the mutant EGFR subgroup. Protein analysis of MAPF-derived exosomes revealed abundant EGFR and p-EGFR components that implied possible transfer to endothelial cells. Concluding Kaplan–Meier analysis and in vitro studies, the results indicated that the addition of bevacizumab on gefitinib treatment could suppress MAPF-induced angiogenesis in lung adenocarcinoma patients.
    Type of Medium: Online Resource
    ISSN: 2227-9059
    URL: Article
    DOI: 10.3390/biomedicines9101327
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2720867-9
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  • 10
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    Biological Inhibitory Effects of the Chinese Herb Danggui on Brain Astrocytoma
    S. Karger AG ; 2006
    In:  Pathobiology Vol. 73, No. 3 ( 2006), p. 141-148
    Details
    In: Pathobiology, S. Karger AG, Vol. 73, No. 3 ( 2006), p. 141-148
    Abstract: 〈 i 〉 Objective: 〈 /i 〉 Previous studies have demonstrated the utility of the traditional Chinese herb danggui in the treatment of chronic myelogenous leukemia. Our aim was to examine whether it might similarly be used to treat glioblastoma multiforme. 〈 i 〉 Methods: 〈 /i 〉 The lipid-soluble active ingredients of danggui were extracted with acetone (AS-AC) or chlorophenol (AS-CH) and their antiproliferative and proapoptotic effects were studiedin vitro on cultured GBM 8401 cells and in vivoon tumors in nude mice. 〈 i 〉 Results: 〈 /i 〉 After a 24-hour treatment, either AS-AC or AS-CH at a lower (50 µg/ml) and a higher concentration (100 µg/ml) significantly inhibited the proliferative activity of GBM 8401 cultured cells by 30–50%, as well as the expression of cathepsin B and vascular endothelial growth factor (VEGF). In nude mice, the growth of the tumor was inhibited by 30% by AS-CH or AS-AC (20 mg/kg; p 〈 0.05) and by 60% by AS-CH or AS-AC (60 mg/kg; p 〈 0.05). AS-AC and AS-CH also significantly inhibited microvessel formation in the tumors of nude mice. 〈 i 〉 Conclusions: 〈 /i 〉 Danggui may inhibit tumor growth by reducing the level of VEGF and the proapoptotic protein, cathepsin B. Thus, danggui may be useful in the treatment of high-grade astrocytomas.
    Type of Medium: Online Resource
    ISSN: 1015-2008 , 1423-0291
    URL: Article
    DOI: 10.1159/000095560
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2006
    detail.hit.zdb_id: 1483541-1
    SSG: 12
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