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PubMed | A-Life Medical, National Defense Medical Center & Tri Service General Hospital, China Medical University at Taichung, Cheng Hsin Hospital and 2 more.
Type: Comparative Study | Journal: Head & neck | Year: 2016

Recent studies suggest that long-term exposure of the carcinogen 4-methylnitrosamino-1-3-pyridyl-1-butanone (NNK) found in tobacco smoke is involved in the progression of head and neck squamous cell carcinoma (HNSCC). The underlying nicotine-mediated mechanism remains unclear.An analysis of SCC-25 and Fadu cells with or without NNK exposure focusing on the evaluation of migration and invasion abilities, the expression of epithelial-mesenchymal transition, drug-resistance-related genes, properties of cancer stem cells (CSCs), and anti-apoptosis was performed.Long-term NNK exposure enhances migration and invasion with morphological alterations in a dose-dependently manner. Furthermore, NNK exposure also upregulates Snail, promotes sphere-forming ability, and overexpresses aldehyde dehydrogenase 1 (ALDH1), Nanog, OCT4, ABCG2, and MDR1.The current study confirmed that long-term NNK exposure plays a role in HNSCC by increasing anti-apoptosis and therapeutic resistance via the Snail-RKIP signaling pathway. Our data also suggest that 7 nicotinic acetylcholine receptor (7-nAChR) inhibition or targeting Snail may provide a feasible rationale for preventing the progression of HNSCC.


PubMed | Chang Gung Memorial Hospital and National Defense Medical Center & Tri Service General Hospital
Type: Journal Article | Journal: PloS one | Year: 2014

Stem cell markers are upregulated in various cancers and have potential as prognostic indicators. The objective of this study was to determine the expression of three stem cell markers, aldehyde dehydrogenase 1 (ALDH-1), B cell-specific Moloney murine leukemia virus integration site 1 (Bmi-1), and Nanog, in esophageal squamous cell carcinoma (ESCC) tissues. Immunohistochemistry was used to measure the expression of ALDH-1, Bmi-1, and Nanog in ESCC tissues from 41 patients who received pre-operative chemoradiation. We evaluated the relationship between expression of these markers, and clinicopathological features, tumor regression grade (TRG), and 5-year overall survival (OS). There were no significant associations of ALDH-1 or Bmi-1 expression with age, gender, clinical stage, and treatments (p>0.05). However, patients with Nanog-positive tumors were significantly older than those whose tumors were Nanog-negative (p=0.033). TRG after treatment was significantly associated with expression of ALDH-1 (p=0.001), Bmi-1 (p=0.004), and Nanog (p<0.001). Although OS was significantly better in patients with low TRGs (p=0.001), there were no significant correlations between ALDH-1, Bmi-1, or Nanog with OS. Expression of ALDH-1, Bmi-1, and Nanog correlated with TRG, but not OS. Further large studies are necessary to fully elucidate the prognostic value of these stem cell markers for ESCC patients.


PubMed | National Defense Medical Center & Tri Service General Hospital
Type: Journal Article | Journal: Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology | Year: 2012

To clarify the efficacy of grape seed procyanidin (GSP) on antiproliferative effects related to p53 functional status of oral squamous cell carcinoma (OSCC) for its chemoadjuvant potential.We used GSP to investigate SCC-25 cells with wild-type p53 gene and OEC-M1 cells with mutant p53 gene for the assessment of antiproliferative effects including cell viability, cell cycle, apoptosis, migration and invasion potential, and alterations of associated oncoproteins involved in cellular and molecular events.The findings suggest that GSP on OEC-M1 cells leads to cell cycle arrest by increasing the expression of p21(Cip1) /p27(Kip1) protein without functioning mitochondria-mediated apoptosis, whereas GSP on SCC-25 cells inhibits cell proliferation via both G1-phase arrest and mitochondria-mediated apoptosis in a dose-dependent manner as a result of alterations of Bcl-2. GSP also inhibits the migration and invasion of both cells, which are associated with the suppression of matrix metalloproteinases (MMPs), MMP-2 and MMP-9.Antiproliferative effectiveness of GSP is closely associated with the p53 status of OSCC cells. GSP displays chemoadjuvant potential via cell cycle blockage and apoptotic induction. Our findings clearly suggest that GSP may play a role as a novel chemopreventive or therapeutic agent for OSCC.


PubMed | National Defense Medical Center Tri service General Hospital
Type: Journal Article | Journal: Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia | Year: 2011

Stereotactic radiosurgery (SRS) has been established as an option for the treatment of trigeminal neuralgia (TN). Here, we report our experience of CyberKnife-based (Accuray, Sunnyvale, CA, USA) stereotactic rhizotomy on medically refractory patients to determine its clinical effectiveness. Between January 2007 and December 2009, 14 selected patients underwent SRS for TN at our CyberKnife Center. Patients were evaluated for pain relief using a visual analog scale (VAS) score, time to reach pain relief (latency), duration of pain control, decrease of pain medication, occurrence of new dysesthesia, and side effects at the 3-month, 6-month, 1-year and 2-year follow-up. A literature analysis revealed that compared with other SRS systems, which can provide a high rate of pain control, CyberKnife stereotactic rhizotomy yielded an earlier onset of pain relief in our cohort.


PubMed | National Defense Medical Center & Tri Service General Hospital
Type: Journal Article | Journal: Acta neurologica Taiwanica | Year: 2010

Tremor is the most common involuntary movement disorder. It can be an isolated symptom or a symptom of another neurological disorder, such as dystonia, Parkinson disease, spinocerebellar ataxia et al. It is an unintentional, somewhat rhythmic, muscle movement involving to-and-fro movements of one or more parts of the body. It can affect the hands, arms, head, vocal cord, jaw, chin, and legs. Most tremors occur in the hands. Clinically, the most useful way to categorized tremor is whether it occurs mainly at rest, on postural, or during movement (kinetic tremor). Tremor is most common classified by different clinical features and cause or origin; include essential tremor, Parkinsonian tremor, cerebellar tremor, dystonic tremor, orthostatic tremor, physiologic tremor, and psychogenic tremor. Diagnosis need a detail history (include familial inheritance, drugs exposure, alcohol consumption or withdraw); complete physical examination and laboratory tests. Electromyography is also a simple and quick method with which to calculate tremor frequency and amplitude for assisting diagnosis. Treatment for majority of tremor syndrome is purely symptomatic, and is similar regardless of the underlying cause of the tremor. There are different medicines to try in order propranolol, clonazepam, primidome and gabapentin for limb tremors, or trihexyphenidyl for dystonic tremor. Focal botulinum toxin injection may be help in focal tremor. Neurosurgery is only indicated in severe tremor, such as deep brain stimulation (DBS) of subthalamic nucleus for primary or secondary parkinsonian tremor.


PubMed | A-Life Medical, National Defense Medical Center & Tri Service General Hospital, China Medical University at Taichung, Taipei Medical University and 3 more.
Type: Journal Article | Journal: Oncotarget | Year: 2016

Treatment failure followed by relapse and metastasis in patients with non-small cell lung cancer is often the result of acquired resistance to cisplatin-based chemotherapy. A cancer stem cell (CSC)-mediated anti-apoptotic phenomenon is responsible for the development of drug resistance. The underlying molecular mechanism related to cisplatin resistance is still controversial, and a new strategy is needed to counteract cisplatin resistance. We used a nonadhesive culture system to generate drug-resistant spheres (DRSPs) derived from cisplatin-resistant H23 lung cancer cells. The expressions of drug-resistance genes, properties of CSCs, and markers of anti-apoptotic proteins were compared between control cells and DRSPs. DRSPs exhibited upregulation of cisplatin resistance-related genes. Gradual morphological alterations showing epithelial-to-mesenchymal transition phenomenon and increased invasion and migration abilities were seen during induction of DRSPs. Compared with control cells, DRSPs displayed increased CSC and anti-apoptotic properties, greater resistance to cisplatin, and overexpression of p-Hsp27 via activation of p38 MAPK signaling. Knockdown of Hsp27 or p38 decreased cisplatin resistance and increased apoptosis in DRSPs. Clinical studies confirmed that the expression of p-Hsp27 was closely associated with prognosis. Overexpression of p-Hsp27 was usually detected in advanced-stage patients with lung cancer and indicated short survival.DRSPs were useful for investigating drug resistance and may provide a practical model for studying the crucial role of p-Hsp27 in the p38 MAPK-Hsp27 axis in CSC-mediated cisplatin resistance. Targeting this axis using siRNA Hsp27 may provide a treatment strategy to improve prognosis and prolong survival in lung cancer patients.


PubMed | Tri Service General Hospital, A-Life Medical, National Defense Medical Center & Tri Service General Hospital, China Medical University at Taichung and 2 more.
Type: Journal Article | Journal: Oncotarget | Year: 2016

A tobacco-specific component, 4-methylnitrosamino-1-3-pyridyl-1-butanone (NNK), is a major risk factor for many cancers. Recent reports have demonstrated that NNK exposure may be associated with tumor progression and chemoresistance in certain cancers. However, the underlying NNK-induced mechanism contributing to the aggressiveness of colorectal cancer (CRC) has not been thoroughly studied. In this study, we used HT29 cells treated with NNK to simulate the long-term exposure of cigarette smoke. A comparative analysis was performed to evaluate cell proliferation, migration, and invasion as well as epithelial-mesenchymal transition (EMT) markers and drug-resistance genes expression, cancer stem cell (CSC) properties, and anti-apoptotic activity. Signaling pathways related to chemoresistance were also investigated. As a result, NNK exposure dose-dependently stimulates cell proliferation, enhance abilities of migration and invasion, induce EMT phenomenon, and attenuate apoptosis. Furthermore, NNK exposure also promotes the capabilities of sphere formation, upregulation of Snail, and overexpression of CD133, Nanog, OCT4, and the drug-resistant genes. Knockdown of Snail results in upregulation of Raf kinase inhibitor protein (RKIP), increased apoptosis, reversal of EMT phenomenon, and reducation of expression of CSC markers, all of which contribute to a decrease of chemoresistance. Our study demonstrates a number of related mechanisms that mediate the effect of NNK exposure on increasing CRC therapeutic resistance via the Snail signaling pathway. Targeting Snail may provide a feasible strategy for the treatment of CRC.

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