324 results on '"Chih-Yen Chien"'
Search Results
2. Prognostic impact of bridge or neoadjuvant induction chemotherapy in patients with resected oral cavity cancer: A nationwide cohort study
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Cheng‐Lung Hsu, Yu‐Wen Wen, Hung‐Ming Wang, Chia‐Hsun Hsieh, Chi‐Ting Liao, Li‐Yu Lee, Shu‐Hang Ng, Chien‐Yu Lin, Wen‐Cheng Chen, Jin‐Ching Lin, Yao‐Te Tsai, Shu‐Ru Lee, Chih‐Yen Chien, Chun‐Hung Hua, Cheng Ping Wang, Tsung‐Ming Chen, Shyuang‐Der Terng, Chi‐Ying Tsai, Kang‐Hsing Fan, Chih‐Hua Yeh, Chih‐Hung Lin, Chung‐Kan Tsao, Nai‐Ming Cheng, Tuan‐Jen Fang, Shiang‐Fu Huang, Chung‐Jan Kang, Li‐Ang Lee, Ku‐Hao Fang, Yu‐Chien Wang, Wan‐Ni Lin, Li‐Jen Hsin, Tzu‐Chen Yen, and Chun‐Ta Liao
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cancer registry ,clinical outcomes ,induction chemotherapy ,oral cavity squamous cell carcinoma ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background While surgery remains the primary treatment for oral squamous cell carcinoma (OCSCC), induction chemotherapy (IC) can be used as a bridging or neoadjuvant therapy. This nationwide study in Taiwan examines the survival outcomes of OCSCC patients who received IC before surgery. Methods We analyzed data from 29,891 patients with OCSCC. Of these, 29,058 initially underwent surgery (OP group), whereas 833 received IC before surgery (IC + OP group). A propensity score (PS)‐matched analysis (4, 1 ratio, 3260 vs. 815 patients) was performed considering tumor subsite, sex, age, Charlson comorbidity index, clinical T1–T4b tumors, clinical N0–3 disease, and clinical stage I–IV. Results In the PS‐matched cohort, the 5‐year disease‐specific survival (DSS) and overall survival (OS) rates were 65% and 57%, respectively. When comparing the OP and IC + OP groups, the 5‐year DSS rates were 66% and 62%, respectively (p = 0.1162). Additionally, the 5‐year OS rates were 57% and 56%, respectively (p = 0.9917). No significant intergroup differences in survival were observed for specific subgroups with cT4a tumors, cT4b tumors, cN3 disease, pT4b tumors, and pN3 disease. However, for patients with pT4a tumors, the OP group demonstrated superior 5‐year outcomes compared to the IC + OP group, with a DSS of 62% versus 52% (p = 0.0006) and an OS of 53% versus 44% (p = 0.0060). Notably, patients with cT2–3, cN1, and c‐Stage II disease in the IC + OP group were significantly more likely to achieve pT0–1 status (p
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- 2024
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3. Prognostic impact of elective tracheotomy in resected oral cavity squamous cell carcinoma: A nationwide cohort study
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Ku‐Hao Fang, Chung‐Jan Kang, Li‐Yu Lee, Shu‐Hang Ng, Chien‐Yu Lin, Wen‐Cheng Chen, Jin‐Ching Lin, Yao‐Te Tsai, Shu‐Ru Lee, Chih‐Yen Chien, Chun‐Hung Hua, Cheng Ping Wang, Tsung‐Ming Chen, Shyuang‐Der Terng, Chi‐Ying Tsai, Hung‐Ming Wang, Chia‐Hsun Hsieh, Kang‐Hsing Fan, Chih‐Hua Yeh, Chih‐Hung Lin, Chung‐Kan Tsao, Nai‐Ming Cheng, Tuan‐Jen Fang, Shiang‐Fu Huang, Li‐Ang Lee, Yu‐Chien Wang, Wan‐Ni Lin, Li‐Jen Hsin, Tzu‐Chen Yen, Yu‐Wen Wen, and Chun‐Ta Liao
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cancer registry ,clinical outcomes ,oral cavity squamous cell carcinoma ,tracheotomy ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Elective tracheotomy is commonly performed in resected oral squamous cell carcinoma (OCSCC) to maintain airway patency. However, the indications for this procedure vary among surgeons. This nationwide study evaluated the impact of tracheotomy on both the duration of in‐hospital stay and long‐term survival outcomes in patients with OCSCC. Methods A total of 18,416 patients with OCSCC were included in the analysis, comprising 7981 patients who underwent elective tracheotomy and 10,435 who did not. The primary outcomes assessed were 5‐year disease‐specific survival (DSS) and overall survival (OS). To minimize potential confounding factors, a propensity score (PS)‐matched analysis was performed on 4301 patients from each group. The duration of hospital stay was not included as a variable in the PS‐matched analysis. Results Prior to PS matching, patients with tracheotomy had significantly lower 5‐year DSS and OS rates compared to those without (71% vs. 82%, p
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- 2024
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4. Comparing the clinical outcomes of initial surgery and primary definitive radiotherapy with a dosage of 6600 cGy or higher in cT1−2N0M0 oral cavity squamous cell carcinoma: A nationwide cohort study
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Chien‐Yu Lin, Wen‐Cheng Chen, Yu‐Wen Wen, Kang‐Hsing Fan, Jin‐Ching Lin, Shu‐Hang Ng, Yao‐Te Tsai, Shu‐Ru Lee, Chung‐Jan Kang, Li‐Yu Lee, Chih‐Yen Chien, Chun‐Hung Hua, Cheng Ping Wang, Tsung‐Ming Chen, Shyuang‐Der Terng, Chi‐Ying Tsai, Hung‐Ming Wang, Chia‐Hsun Hsieh, Chih‐Hua Yeh, Chih‐Hung Lin, Chung‐Kan Tsao, Nai‐Ming Cheng, Tuan‐Jen Fang, Shiang‐Fu Huang, Li‐Ang Lee, Ku‐Hao Fang, Yu‐Chien Wang, Wan‐Ni Lin, Li‐Jen Hsin, Tzu‐Chen Yen, and Chun‐Ta Liao
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cancer registry ,clinical outcomes ,cT1−2N0M0 ,definite radiotherapy ,oral cavity squamous cell carcinoma ,surgery ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background To compare the clinical outcomes of two treatment modalities, initial surgery and primary definitive radiotherapy (RT), in Taiwanese patients diagnosed with cT1−2N0M0 oral cavity squamous cell carcinoma (OCSCC). Methods Between 2011 and 2019, we analyzed data for 13,542 cT1−2N0M0 patients who underwent initial surgery (n = 13,542) or definitive RT with a dosage of at least 6600 cGy (n = 145) for the treatment of OCSCC. To account for baseline differences, we employed propensity score (PS) matching, resulting in two well‐balanced study groups (initial surgery, n = 580; definitive RT, n = 145). Results Before PS matching, the 5‐year disease‐specific survival (DSS) rates were 88% for the surgery group and 58% for the RT group. After PS matching, the 5‐year DSS rates of the two groups were 86% and 58%, respectively. Similarly, the 5‐year overall survival (OS) rates before PS matching were 80% for the surgery group and 36% for the RT group, whereas after PS matching, they were 73% and 36%, respectively. All these differences were statistically significant (p
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- 2024
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5. Quality assurance for focused ultrasound-induced blood-brain barrier opening procedure using passive acoustic detectionResearch in context
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Chih-Yen Chien, Lu Xu, Jinyun Yuan, Siaka Fadera, Andrew H. Stark, Umeshkumar Athiraman, Eric C. Leuthardt, and Hong Chen
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Passive acoustic detection ,Quality assurance ,Blood-brain barrier opening ,Focused ultrasound ,Clinical FUS device ,Acoustic coupling ,Medicine ,Medicine (General) ,R5-920 - Abstract
Summary: Background: Focused ultrasound (FUS) combined with microbubbles is a promising technique for noninvasive, reversible, and spatially targeted blood-brain barrier opening, with clinical trials currently ongoing. Despite the fast development of this technology, there is a lack of established quality assurance (QA) strategies to ensure procedure consistency and safety. To address this challenge, this study presents the development and clinical evaluation of a passive acoustic detection-based QA protocol for FUS-induced blood-brain barrier opening (FUS-BBBO) procedure. Methods: Ten glioma patients were recruited to a clinical trial for evaluating a neuronavigation-guided FUS device. An acoustic sensor was incorporated at the center of the FUS device to passively capture acoustic signals for accomplishing three QA functions: FUS device QA to ensure the device functions consistently, acoustic coupling QA to detect air bubbles trapped in the acoustic coupling gel and water bladder of the transducer, and FUS procedure QA to evaluate the consistency of the treatment procedure. Findings: The FUS device passed the device QA in 9/10 patient studies. 4/9 cases failed acoustic coupling QA on the first try. The acoustic coupling procedure was repeatedly performed until it passed QA in 3/4 cases. One case failed acoustic coupling QA due to time constraints. Realtime passive cavitation monitoring was performed for FUS procedure QA, which captured variations in FUS-induced microbubble cavitation dynamics among patients. Interpretation: This study demonstrated that the proposed passive acoustic detection could be integrated with a clinical FUS system for the QA of the FUS-BBBO procedure. Funding: National Institutes of Health R01CA276174, R01MH116981, UG3MH126861, R01EB027223, R01EB030102, and R01NS128461.
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- 2024
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6. The prognostic utility of preoperative geriatric nutritional risk index on survival outcomes of locally advanced oral cancer
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Yi-Lun Shih, Hui-Ching Chuang, Yu-Tsai Lin, Chih-Yen Chien, Chao-Hui Yang, Chi-Chih Lai, Yan-Ye Su, Yao-Te Tsai, Hui Lu, and Ming-Hsien Tsai
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Geriatric nutritional risk index ,Oral cancer ,Advanced stage ,Nutrition ,Prognosis ,Medicine (General) ,R5-920 - Abstract
Purpose: This retrospective cohort study was to assess the prognostic value of preoperative geriatric nutritional risk index (GNRI) on survival outcomes for patients with locally advanced oral squamous cell carcinoma (LAOSCC). Methods: Patients with LAOSCC receiving upfront radical surgery at a single institute from January 2007 to February 2017 were enrolled. The primary outcomes in the study were 5-year overall survival (OS) and cancer-specific survival (CSS) rates, and a nomogram based on GNRI and other clinical-pathological factors was established for individualized OS prediction. Results: There were 343 patients enrolled in this study. The optimal cut-off value of GNRI was observed to be 97.8. Patients in the high-GNRI group (GNRI ≥97.8) had statistically significantly better outcomes in 5-year OS (74.7% vs. 57.2%, p = 0.001) and CSS (82.2% vs. 68.9%, p = 0.005) when compared with the low-GNRI group (GNRI
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- 2023
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7. Reply to comment on 'The prognostic utility of preoperative geriatric nutritional risk index on survival outcomes of locally advanced oral cancer'
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Ming-Hsien Tsai, Hui Lu, and Chih-Yen Chien
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Medicine (General) ,R5-920 - Published
- 2023
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8. Clinical validation of a saliva-based matrix metalloproteinase-1 rapid strip test for detection of oral cavity cancer
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Lichieh Julie Chu, Ya-Ting Chang, Chih-Yen Chien, Hui-Ching Chung, Shu-Fang Wu, Chih-Jou Chen, Yen-Chun Liu, Wei-Chao Liao, Chien-Hua Chen, Wei-Fan Chiang, Kai-Ping Chang, Jun-Sheng Wang, and Jau-Song Yu
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Salivary biomarker ,MMP-1 ,Oral cancer diagnosis ,Point of care ,ELISA ,Rapid strip test ,Medicine (General) ,R5-920 ,Biology (General) ,QH301-705.5 - Abstract
Background: We previously identified matrix metalloproteinase-1 (MMP-1) as one of the most promising salivary biomarkers for oral squamous cell carcinoma (OSCC) and developed a sensitive ELISA for MMP-1 with good performance in detection of OSCC using a cohort of 1160 saliva samples. Methods: A time-saving rapid strip test (RST) for MMP-1 was developed in this study and its diagnostic performance compared with ELISA using saliva samples from a new cohort of 603 subjects (171 healthy controls, 236 patients with oral potentially malignant disorders, and 196 OSCC patients). Results: Salivary MMP-1 levels measured using RST and ELISA were highly comparable and both assays could effectively distinguish between OSCC and non-cancerous groups. Similar to ELISA, receiver operating characteristic curve analysis of the MMP-1 RST was effective in identifying patients with OSCC at different oral cavity sites and stages. Conclusions: Salivary MMP-1 can be sensitively detected using both RST and ELISA methods. Our newly developed point-of-care MMP-1 RST is a promising in vitro diagnostic device (IVD) that may serve as a novel auxiliary tool in the routine clinical detection and monitoring of OSCC.
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- 2024
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9. Is elective neck dissection justified in cT2N0M0 oral cavity cancer defined according to the AJCC eighth edition staging system?
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Tsung‐Ming Chen, Shyuang‐Der Terng, Li‐Yu Lee, Shu‐Ru Lee, Shu‐Hang Ng, Chung‐Jan Kang, Jin‐Ching Lin, Chih‐Yen Chien, Chun‐Hung Hua, Cheng Ping Wang, Wen‐Cheng Chen, Yao‐Te Tsai, Chi‐Ying Tsai, Chien‐Yu Lin, Kang‐Hsing Fan, Hung‐Ming Wang, Chia‐Hsun Hsieh, Chih‐Hua Yeh, Chih‐Hung Lin, Chung‐Kan Tsao, Nai‐Ming Cheng, Tuan‐Jen Fang, Shiang‐Fu Huang, Li‐Ang Lee, Ku‐Hao Fang, Yu‐Chien Wang, Wan‐Ni Lin, Li‐Jen Hsin, Tzu‐Chen Yen, Yu‐Wen Wen, and Chun‐Ta Liao
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cancer registry ,clinical outcomes ,cT2N0M0 ,elective neck dissection ,occult lymph node metastasis ,oral cavity squamous cell carcinoma ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background The current NCCN guidelines recommend considering elective neck dissection (END) for early‐stage oral cavity squamous cell carcinoma (OCSCC) with a depth of invasion (DOI) exceeding 3 mm. However, this DOI threshold, determined by evaluating the occult lymph node metastatic rate, lacks robust supporting evidence regarding its impact on patient outcomes. In this nationwide study, we sought to explore the specific indications for END in patients diagnosed with OCSCC at stage cT2N0M0, as defined by the AJCC Eighth Edition staging criteria. Methods We examined 4723 patients with cT2N0M0 OCSCC, of which 3744 underwent END and 979 were monitored through neck observation (NO). Results Patients who underwent END had better 5‐year outcomes compared to those in the NO group. The END group had higher rates of neck control (95% vs. 84%, p
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- 2024
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10. First-in-human prospective trial of sonobiopsy in high-grade glioma patients using neuronavigation-guided focused ultrasound
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Jinyun Yuan, Lu Xu, Chih-Yen Chien, Yaoheng Yang, Yimei Yue, Siaka Fadera, Andrew H. Stark, Katherine E. Schwetye, Arash Nazeri, Rupen Desai, Umeshkumar Athiraman, Aadel A. Chaudhuri, Hong Chen, and Eric C. Leuthardt
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Sonobiopsy is an emerging technology that combines focused ultrasound (FUS) with microbubbles to enrich circulating brain disease-specific biomarkers for noninvasive molecular diagnosis of brain diseases. Here, we report the first-in-human prospective trial of sonobiopsy in high-grade glioma patients to evaluate its feasibility and safety in enriching plasma circulating tumor biomarkers. A nimble FUS device integrated with a clinical neuronavigation system was used to perform sonobiopsy following an established clinical workflow for neuronavigation. Analysis of blood samples collected before and after FUS sonication showed that sonobiopsy enriched plasma circulating tumor DNA (ctDNA), including a maximum increase of 1.6-fold for the mononucleosome cell-free DNA (cfDNA) fragments (120–280 bp), 1.9-fold for the patient-specific tumor variant ctDNA level, and 5.6-fold for the TERT mutation ctDNA level. Histological analysis of surgically resected tumors confirmed the safety of the procedure. Transcriptome analysis of sonicated and nonsonicated tumor tissues found that FUS sonication modulated cell physical structure-related genes. Only 2 out of 17,982 total detected genes related to the immune pathways were upregulated. These feasibility and safety data support the continued investigation of sonobiopsy for noninvasive molecular diagnosis of brain diseases.
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- 2023
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11. Transcranial focused ultrasound-induced blood‒brain barrier opening in mice without shaving hairs
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Lu Xu, Yan Gong, Chih-Yen Chien, Eric Leuthardt, and Hong Chen
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Medicine ,Science - Abstract
Abstract Acoustic coupling through hairs remains a challenge to performing transcranial-focused ultrasound procedures. Here, we demonstrated that this challenge could be addressed by using oil as the coupling medium, leveraging oil's high affinity to hairs due to their inherent hydrophobicity. We compared focused ultrasound-induced blood–brain barrier opening (FUS-BBBO) outcomes in mice under three coupling conditions: oil with hairs (“oil + hairs”), ultrasound gel with hair shaving (“ultrasound gel + no hair”), and ultrasound gel with hairs (“ultrasound gel + hairs”). The quality of the coupling was evaluated by $${\mathrm{T}}_{2}$$ T 2 -weighted magnetic resonance imaging (MRI) and passive cavitation detection (PCD). The outcome of FUS-BBBO was assessed by MRI contrast agent extravasation using in vivo $${\mathrm{T}}_{1}$$ T 1 -weighted contrast-enhanced MRI. It was also evaluated by ex vivo fluorescence imaging of the mouse brain after intravenous injection of a model drug, Evans blue. The results showed that “oil + hairs” consistently achieved high-quality acoustic coupling without trapping air bubbles. The FUS-BBBO outcome was not significantly different between the “oil + hairs” and the “ultrasound gel + no hair” groups. These two groups had significantly higher levels of BBB opening than the “ultrasound gel + hairs” group. This study demonstrated that oil could be a coupling medium for transcranial FUS procedures without shaving hairs.
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- 2023
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12. Stereotactic body radiotherapy plus cetuximab for previously irradiated un-resectable head and neck cancer
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Tai-Lin Huang, Hui-Ching Chuang, Ming-Hsien Tsai, Chih-Yen Chien, Yan-Ye Su, Yu-Tsai Lin, Chao-Hui Yang, Chi-Chih Lai, Shau-Hsuan Li, and Fu-Min Fang
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Head and neck squamous cell carcinoma ,Stereotactic body radiotherapy ,Cetuximab ,Gross tumor volume ,Re-irradiation ,PET-CT ,Medicine (General) ,R5-920 ,Biology (General) ,QH301-705.5 - Abstract
Background: The aim of the study was to explore the treatment outcomes and prognostic factors for patients with previously irradiated but unresectable recurrent head and neck squamous cell carcinoma (rHNSCC) treated by stereotactic body radiotherapy (SBRT) plus cetuximab at a single institute in Taiwan. Methods: From February 2016 to March 2019, 74 patients with previously irradiated but unresectable rHNSCC were treated with SBRT plus cetuximab. All patients received irradiation to the gross tumor and/or nodal area with 40–50 Gy in five fractions, with each fraction interval ≥2 days over a 2-week period by using the CyberKnife M6 machine. An18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) scan was performed before treatment for treatment target delineation (n = 74) and 2 months later for response evaluation (n = 60). The median follow-up time was 9 months (range 1–36 months). Results: The treatment response rate was complete response: 25.0%, partial response: 41.7%, stable disease: 11.7%, and progressive disease: 21.7% based on the criteria of the Response Evaluation Criteria in Solid Tumors (n = 72) and complete metabolic response: 21.7%, partial metabolic response: 51.7%, stable metabolic disease: 13.3%, and progressive metabolic disease: 13.3% based on PET-CT (n = 60), respectively. The 1-/2-year overall survival (OS) and progression-free survival (PFS) rates were 42.8%/22.0% and 40.5%/19.0%, respectively. In the logistic regression model, a re-irradiation interval >12 months was observed to be the only significant prognostic factor for a favorable treatment response. In the Cox proportional hazards model, a re-irradiation interval >12 months and gross tumor volume (GTV) ≦ 50 ml were favorable prognostic factors of OS and PFS. Conclusion: SBRT plus cetuximab provides a promising salvage strategy for those patients with previously irradiated but unresectable rHNSCC, especially those with a re-irradiation interval >12 months or GTV ≦ 50 ml.
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- 2022
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13. Blood–brain barrier opening in a large animal model using closed-loop microbubble cavitation-based feedback control of focused ultrasound sonication
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Chih-Yen Chien, Lu Xu, Christopher Pham Pacia, Yimei Yue, and Hong Chen
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Medicine ,Science - Abstract
Abstract Focused ultrasound (FUS) in combination with microbubbles has been established as a promising technique for noninvasive and localized Blood–brain barrier (BBB) opening. Real-time passive cavitation detection (PCD)-based feedback control of the FUS sonication is critical to ensure effective BBB opening without causing hemorrhage. This study evaluated the performance of a closed-loop feedback controller in a porcine model. Calibration of the baseline cavitation level was performed for each targeted brain location by a FUS sonication in the presence of intravenously injected microbubbles at a low acoustic pressure without inducing BBB opening. The target cavitation level (TCL) was defined for each target based on the baseline cavitation level. FUS treatment was then performed under real-time PCD-based feedback controller to maintain the cavitation level at the TCL. After FUS treatment, contrast-enhanced MRI and ex vivo histological staining were performed to evaluate the BBB permeability and safety. Safe and effective BBB opening was achieved with the BBB opening volume increased from 3.8 ± 0.7 to 53.6 ± 23.3 mm3 as the TCL was increased from 0.25 to 1 dB. This study validated that effective and safe FUS-induced BBB opening in a large animal model can be achieved with closed-loop feedback control of the FUS sonication.
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- 2022
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14. Patients of stage I oral cancer with pathologically low‐risk feature managed by primary tumor resection alone: Impact of depth of invasion and a nomogram analysis
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Ming‐Hsien Tsai, Hui‐Shan Huang, Hui‐Ching Chuang, Yu‐Tsai Lin, Kun‐Lin Yang, Hui Lu, and Chih‐Yen Chien
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depth of invasion ,neck dissection ,outcome ,regional recurrence ,stage I oral cancer ,Otorhinolaryngology ,RF1-547 ,Surgery ,RD1-811 - Abstract
Abstract Objectives To evaluate the importance of depth of invasion (DOI) in patients with pathologically low‐risk feature stage I oral squamous cell carcinoma (OSCC) managed by primary tumor resection alone. Methods Patients with stage I OSCC, at pathologically low risk, underwent primary tumor resection without neck dissection were enrolled retrospectively between 2007 and 2015. Low risk was defined as the absence of positive or close margins, lymphovascular invasion, perineural invasion, worst pattern of invasion‐5, and poor differentiation in histologic grade. The primary endpoints included overall survival (OS), cancer specific survival (CSS), local recurrence free survival (LRFS), and regional recurrence free survival (RRFS). A nomogram based on the DOI was established for predicting RRFS. Results A total of 198 patients were enrolled in this study. DOI was the only prognosticator to achieve statistical significance in all primary endpoints according to univariate analysis. Patients with DOI
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- 2022
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15. DRP1 contributes to head and neck cancer progression and induces glycolysis through modulated FOXM1/MMP12 axis
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Tai‐Lin Huang, Chuang‐Rung Chang, Chih‐Yen Chien, Gong‐Kai Huang, Yi‐Fan Chen, Li‐Jen Su, Hsin‐Ting Tsai, Yu‐Sheng Lin, Fu‐Min Fang, and Chang‐Han Chen
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DRP1 ,FOXM1 ,glycolysis ,head and neck cancer ,miR‐575 ,MMP12 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abnormal DRP1 expression has been identified in a variety of human cancers. However, the prognostic potential and mechanistic role of DRP1 in head and neck cancer (HNC) are currently poorly understood. Here, we demonstrated a significant upregulation of DRP1 in HNC tissues, and that DRP1 expression correlates with poor survival of HNC patients. Diminished DRP1 expression suppressed tumor growth and metastasis in both in vitro and in vivo models. DRP1 expression was positively correlated with FOXM1 and MMP12 expression in HNC patient samples, suggesting pathological relevance in the context of HNC development. Moreover, DRP1 depletion affected aerobic glycolysis through the downregulation of glycolytic genes, and overexpression of MMP12 in DRP1‐depleted cells could help restore glucose consumption and lactate production. Using ChIP‐qPCR, we showed that DRP1 modulates FOXM1 expression, which can enhance MMP12 transcription by binding to its promoter. We also showed that miR‐575 could target 3’UTR of DRP1 mRNA and suppress DRP1 expression. Collectively, our study provides mechanistic insights into the role of DRP1 in HNC and highlights the potential of targeting the miR‐575/DRP1/FOXM1/MMP12 axis as a novel therapy for the prevention of HNC progression.
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- 2022
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16. Focused Ultrasound-Mediated Delivery of Anti-Programmed Cell Death-Ligand 1 Antibody to the Brain of a Porcine Model
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Siaka Fadera, Chinwendu Chukwu, Andrew H. Stark, Yimei Yue, Lu Xu, Chih-Yen Chien, Jinyun Yuan, and Hong Chen
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focused ultrasound ,immunotherapy ,immune checkpoint inhibitors ,blood-brain barrier ,brain drug delivery ,Pharmacy and materia medica ,RS1-441 - Abstract
Immune checkpoint inhibitor (ICI) therapy has revolutionized cancer treatment by leveraging the body’s immune system to combat cancer cells. However, its effectiveness in brain cancer is hindered by the blood-brain barrier (BBB), impeding the delivery of ICIs to brain tumor cells. This study aimed to assess the safety and feasibility of using focused ultrasound combined with microbubble-mediated BBB opening (FUS-BBBO) to facilitate trans-BBB delivery of an ICI, anti-programmed cell death-ligand 1 antibody (aPD-L1) to the brain of a large animal model. In a porcine model, FUS sonication of targeted brain regions was performed after intravenous microbubble injection, which was followed by intravenous administration of aPD-L1 labeled with a near-infrared fluorescent dye. The permeability of the BBB was evaluated using contrast-enhanced MRI in vivo, while fluorescence imaging and histological analysis were conducted on ex vivo pig brains. Results showed a significant 4.8-fold increase in MRI contrast-enhancement volume in FUS-targeted regions compared to nontargeted regions. FUS sonication enhanced aPD-L1 delivery by an average of 2.1-fold, according to fluorescence imaging. In vivo MRI and ex vivo staining revealed that the procedure did not cause significant acute tissue damage. These findings demonstrate that FUS-BBBO offers a noninvasive, localized, and safe delivery approach for ICI delivery in a large animal model, showcasing its potential for clinical translation.
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- 2023
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17. Prognostic stratification of patients with AJCC 2018 pN1 disease in stage III oral squamous cell carcinoma
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Ming-Hsien Tsai, Hui-Ching Chuang, Yu-Tsai Lin, Tai-Lin Huang, Fu-Min Fang, Hui Lu, and Chih-Yen Chien
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Single nodal metastasis ,N1 ,Stage III ,Oral cancer ,Prognosis ,Surgery ,RD1-811 - Abstract
Abstract Background Oral cancer with pT1-3N1 without extracapsular extension of the lymph node is classified as stage III according to the eighth edition of the AJCC staging system. Outcomes of a subgroup of patients classified as having stage III oral cancer with single nodal metastasis are observed to be various clinically. Therefore, such clinical outcomes for subgroup analyses in this cohort are necessary. Methods Patients with pT1-3N1 (based on the eighth edition of the AJCC staging system) oral cancer who underwent surgery between 2007 and 2016 were enrolled retrospectively for survival analyses. Results A total of 105 patients—including 28 patients with pT1N1 disease and 77 patients with pT2-3N1 disease—participated in the study. Pathological T classification was the only statistically significant prognosticator according to univariate analysis. The patients with pT1N1 disease showed better 5-year overall survival (OS), disease specific survival (DSS), and disease free survival (DFS) than those with pT2-3N1 disease (pT1N1 vs pT2-3N1, OS: 96.4% vs 72.2%, p = 0.004; DSS: 96.4% vs 77.3%, p = 0.021; DFS: 84.6% vs 62.3%, p = 0.023). Besides, there was no potential clinicopathological confounder which is significant associated with different pathological T classifications in this unique cohort. Conclusions Patients in the pT1N1 subgroup have significantly favorable prognosis than those with pT2-3N1 disease. Down-staging and reclassifying pT1N1 subgroup patients with oral cancer may be considered in tumor staging. Graphical Abstract
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- 2022
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18. Systemic and Local Effects Among Patients With Betel Quid-Related Oral Cancer
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Hui-Ching Chuang MD, PhD, FACS, Ming-Hsien Tsai MD, Yu-Tsai Lin MD, MS, FACS, Ming-Huei Chou PhD, Kun-Lin Yang MD, and Chih-Yen Chien MD, FACS
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
The major predisposing factors of developing oral cancer include smoking, alcohol drinking, and betel quid chewing. Betel quid chewing could cause the abrasion and damage of oral mucosa by crude fibers, chemical insults by additive slaked lime, and arecoline from areca nut. These would lead to the local consequence of oral submucosal fibrosis, which is regarded clinically as a precancer lesion and a major cause of trismus. In addition, the components and additives in betel quid contain chemical toxins and carcinogens, which would further affect the oral mucosa and gradually develop a malignancy. Following literature review, aside from having a greater total tumor burden and more local diseases in the oral cavity and digestive tract, patients with betel quid-related oral cancer also have more systemic diseases from metabolic syndrome, hypertension, cardiovascular disease, type II diabetes mellitus, and obesity than those without this habit. In conclusion, those patients who have the history of smoking, alcohol drinking, and betel quid chewing would present much more unique clinical characteristics than those who only have a history of smoking and alcohol drinking. More attention should therefore be paid to pretreatment evaluation, treatment strategy, and posttreatment follow-up among betel quid chewers.
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- 2022
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19. Optimizing margin status for improving prognosis in patients with oral cavity squamous cell carcinoma: A retrospective study from the two highest-volume Taiwanese hospitals
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Chun-Ta Liao, Li-Yu Lee, Shu-Ru Lee, Shu-Hang Ng, Tsang-Wu Liu, Chih-Yen Chien, Jin-Ching Lin, Cheng Ping Wang, Shyuang-Der Terng, Chun-Hung Hua, Tsung-Ming Chen, Wen-Cheng Chen, Yao-Te Tsai, Chung-Jan Kang, Chi-Ying Tsai, Ying-Hsia Chu, Chien-Yu Lin, Kang-Hsing Fan, Hung-Ming Wang, Chia-Hsun Hsieh, Chih-Hua Yeh, Chih-Hung Lin, Chung-Kan Tsao, Tzu-Chen Yen, Nai-Ming Cheng, Tuan-Jen Fang, Shiang-Fu Huang, Li-Ang Lee, Ku-Hao Fang, Yu-Chien Wang, Wan-Ni Lin, Li-Jen Hsin, and Yu-Wen Wen
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oral cavity squamous cell carcinoma ,volume-outcome ,hospital volumes ,cancer registry ,propensity score matching ,survival outcomes ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
BackgroundIn the treatment of oral cavity squamous cell carcinoma (OCSCC), surgical quality measures which are expected to affect outcomes, including the achievement of a clear margin, are surgeon-dependent but might not be invariably associated with hospital volume. Our objective was to explore surgical margin variations and survival differences of OCSCC between two highest-volume hospitals in Taiwan.Materials and methodsA total of 2009 and 1019 patients with OCSCC who were treated at the two highest-volume Taiwanese hospitals (termed Hospital 1 and Hospital 2, respectively) were included. We examined how a pathological margin
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- 2022
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20. Overexpression of UTX promotes tumor progression in Oral tongue squamous cell carcinoma patients receiving surgical resection: a case control study
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Yen-Hao Chen, Chang-Han Chen, Chih-Yen Chien, Yan-Ye Su, Sheng-Dean Luo, and Shau-Hsuan Li
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UTX ,Tongue cancer ,Squamous cell carcinoma ,Surgery ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Ubiquitously transcribed tetratricopeptide repeat on chromosome X (UTX) has been identified as a histone 3 lysine 27 (H3K27) demethylase and acted as a tumor suppressor gene or oncogenic function. The current study was to explore the significance of UTX in oral tongue squamous cell carcinoma (OTSCC) patients who received surgical resection. Methods A total of 148 OTSCC patients who underwent surgical resection were identified, including 64 patients (43%) with overexpression of UTX and 84 patients (57%) harboring low expression of UTX. We also used two OTSCC cell lines, SAS and Cal 27, to determine the modulation of cancer. Chi-square test was used to investigate the difference of categorical variables between the groups; survival outcome was analyzed using the Kaplan–Meier method in univariate analysis, and a Cox regression model was performed for multivariate analyses. Results Univariate and multivariate analyses showed overexpression of UTX were significantly related to worse disease-free survival (P = 0.028) and overall survival (P = 0.029). The two OTSCC cell lines were treated with GSK-J4, a potent inhibitor of UTX, and transwell migration and invasion assays showed an inhibitory effect with a dose-dependent manner. In addition, western blot analyses also revealed the inhibition of cell cycle and epithelial-mesenchymal transition. Conclusion Our study suggests that UTX plays an important role in the process of OTSCC and overexpression of UTX may predict poor prognosis in OTSCC patients who received surgical resection.
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- 2021
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21. JMJD3 suppresses tumor progression in oral tongue squamous cell carcinoma patients receiving surgical resection
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Yen-Hao Chen, Chang-Han Chen, Chih-Yen Chien, Yan-Ye Su, Sheng-Dean Luo, and Shau-Hsuan Li
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JMJD3 ,Oral tongue cancer ,Squamous cell carcinoma ,Surgery ,Medicine ,Biology (General) ,QH301-705.5 - Abstract
Background Jumonji domain-containing-3 (JMJD3) is reported to be a histone H3 lysine 27 (H3K27) demethylase and a tumor suppressor gene. The present study designed to investigate the crucial role of JMJD3 in oral tongue squamous cell carcinoma (OTSCC) patients who received surgical resection. Methods We enrolled a total of 156 OTSCC patients receiving surgical resection, including 73 patients (47%) with high expression of JMJD3 and 83 patients (53%) harboring low expression of JMJD3. Two OTSCC cell lines, SAS and Cal 27, were used to explore the modulation of cancer. GSK-J4, a potent inhibitor of JMJD3, was used to treat the two OTSCC cell lines. The Chi-square test was performed to examine between-group differences in categorical variables; the Kaplan–Meier method was used to investigate survival outcome in univariate analysis, and the Cox regression model was used for multivariate analysis. Results The median follow-up period was 59.2 months and he five-year disease-free survival (DFS) and overall survival (OS) rates were 46.2% and 50.0%, respectively. Better five-year DFS (59% versus 35%) and five-year OS (63% versus 39%) were mentioned in patients with high expression of JMJD3 compared to those with low expression of JMJD3. High expression of JMJD3 was significantly associated with superior DFS and OS in the univariate and multivariate analyses. Following successful inhibition of JMJD3 by GSK-J4, western blotting analysis showed the decreased expression of Rb and p21. Conclusion Our study showed that high expression of JMJD3 is a good prognostic factor in OTSCC patients who underwent surgical resection.
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- 2022
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22. Low p16 Cytoplasmic Staining Predicts Poor Treatment Outcome in Patients with p16-Negative Locally Advanced Head and Neck Squamous Cell Carcinoma Receiving TPF Induction Chemotherapy
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Yen-Hao Chen, Chih-Yen Chien, Tai-Ling Huang, Tai-Jen Chiu, Yu-Ming Wang, Fu-Min Fang, and Shau-Hsuan Li
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p16 ,head and neck cancer ,squamous cell carcinoma ,induction chemotherapy ,TPF ,Biology (General) ,QH301-705.5 - Abstract
Human papillomavirus (HPV) has been proven to be associated with head and neck squamous cell carcinoma (HNSCC), and diffuse p16 unclear staining is usually considered as HPV-positive. The aim of the current study was to investigate the role of p16 cytoplasmic staining in HNSCC prognosis. A total of 195 HNSCC patients who received docetaxel, cisplatin, and 5-fluouracil (TPF) induction chemotherapy followed by chemoradiotherapy were enrolled. The status of p16 cytoplasmic staining was determined using immunohistochemistry. The median follow-up was 26.0 months for the whole study population and 90.3 months for 51 living survivors. p16 cytoplasmic staining was low in 108 patients and high in 87 patients. Low expression of p16 cytoplasmic staining and primary tumor location in the oral cavity were both independent factors indicating a worse response rate to TPF induction chemotherapy in the univariate and multivariate analyses. The logistic regression model also showed that low expression of p16 cytoplasmic staining and clinical N2–3 status were independent prognostic factors for worse progression-free survival and overall survival. Our study showed that p16 cytoplasmic staining could predict the treatment response to TPF induction chemotherapy and is an independent prognostic factor of survival in HNSCC.
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- 2023
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23. Blood-Brain Barrier Opening by Individualized Closed-Loop Feedback Control of Focused Ultrasound
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Chih-Yen Chien, Yaoheng Yang, Yan Gong, Yimei Yue, and Hong Chen
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Medical technology ,R855-855.5 ,Biotechnology ,TP248.13-248.65 - Abstract
Objective and Impact Statement. To develop an approach for individualized closed-loop feedback control of microbubble cavitation to achieve safe and effective focused ultrasound in combination with microbubble-induced blood-brain barrier opening (FUS-BBBO). Introduction. FUS-BBBO is a promising strategy for noninvasive and localized brain drug delivery with a growing number of clinical studies currently ongoing. Real-time cavitation monitoring and feedback control are critical to achieving safe and effective FUS-BBBO. However, feedback control algorithms used in the past were either open-loop or without consideration of baseline cavitation level difference among subjects. Methods. This study performed feedback-controlled FUS-BBBO by defining the target cavitation level based on the baseline stable cavitation level of an individual subject with “dummy” FUS sonication. The dummy FUS sonication applied FUS with a low acoustic pressure for a short duration in the presence of microbubbles to define the baseline stable cavitation level that took into consideration of individual differences in the detected cavitation emissions. FUS-BBBO was then achieved through two sonication phases: ramping-up phase to reach the target cavitation level and maintaining phase to control the stable cavitation level at the target cavitation level. Results. Evaluations performed in wild-type mice demonstrated that this approach achieved effective and safe trans-BBB delivery of a model drug. The drug delivery efficiency increased as the target cavitation level increased from 0.5 dB to 2 dB without causing vascular damage. Increasing the target cavitation level to 3 dB and 4 dB increased the probability of tissue damage. Conclusions. Safe and effective brain drug delivery was achieved using the individualized closed-loop feedback-controlled FUS-BBBO.
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- 2022
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24. Treatment patterns and survival outcomes of advanced hypopharyngeal squamous cell carcinoma
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Yao-Te Tsai, Wen-Cheng Chen, Chih-Yen Chien, Cheng-Ming Hsu, Yi-Chan Lee, Ming-Shao Tsai, Meng-Hung Lin, Chia-Hsuan Lai, and Kai-Ping Chang
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Head and neck ,Cancer ,Hypopharynx ,Squamous cell carcinoma ,Prognosis ,Surgery ,RD1-811 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background This study evaluated the treatment outcomes of the primary surgery (PS) or concurrent chemoradiotherapy (CCRT) as the initial treatment for hypopharyngeal squamous cell carcinoma (HPSCC). Methods This retrospective cohort study included patients with stages III–IV HPSCC from four tertiary referral centers consecutively enrolled from 2003 to 2012; of them, 213 (32.6%) and 439 (67.4%) had received PS and CCRT as their primary treatments, respectively. The 5-year overall survival (OS) and disease-free survival (DFS) rates were analyzed using the Kaplan–Meier method and Cox regression models. Results In patients undergoing PS and CCRT, OS rates were 45.0% and 33.1% (p < 0.001), respectively, and DFS rates were 36.2% and 28.9% (p = 0.003), respectively. In subgroup analysis, in patients with stage IVA HPSCC, PS was associated with higher OS rate (p = 0.002), particularly in those with T4 or N2 classification (p = 0.021 and 0.002, respectively). Multivariate analysis indicated that stage IVA HPSCC, stage IVB HPSCC, and CCRT were independent adverse prognostic factors for OS rate (p = 0.004, < 0.001, and 0.014, respectively). Furthermore, in patients with stage IVA HPSCC aged ≥ 65 years and with N2 classification, CCRT was significantly associated with lower OS rates than was PS (p = 0.027 and 0.010, respectively). Conclusions In patients with advanced HPSCC, PS was significantly associated with better prognosis than CCRT. PS could be a favorable primary treatment modality for the management of patients with stage IVA HPSCC, particularly those aged ≥ 65 years and with T4 and N2 classification.
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- 2020
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25. Quality of life and survival outcome for patients with nasopharyngeal carcinoma treated by volumetric-modulated arc therapy versus intensity-modulated radiotherapy
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Tai-Lin Huang, Ming-Hsien Tsai, Hui-Ching Chuang, Chih-Yen Chien, Yu-Tsai Lin, Wen-Ling Tsai, and Fu-Min Fang
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Nasopharyngeal carcinoma ,Quality of life ,Volumetric-modulated arc therapy ,Intensity-modulated radiotherapy ,EORTC ,Medical physics. Medical radiology. Nuclear medicine ,R895-920 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background To evaluate the longitudinal changes of quality of life (QoL) and survival in patients with nasopharyngeal carcinoma (NPC) treated by volumetric-modulated arc therapy (VMAT) versus intensity-modulated radiotherapy (IMRT). Methods One hundred and forty non-distant metastatic NPC patients treated by VMAT (n = 66) or IMRT (n = 74) with simultaneously integrated boost between March 2013 and December 2015 at a single institute were analyzed. QoL was prospectively assessed by the EORTC QLQ-C30 and HN35 questionnaires at the four time points: before RT, RT 42.4 Gy (20 fractions), and 3, 12 months after RT. Results The 3-year locoregional relapse-free survival, distant metastasis-free survival, failure-free survival, and overall survival rates were 96.6, 89.4, 86.1%, and 87.4 for the VMAT group, respectively, compared with 91.4, 90.0, 79.8, and 91.3% for the IMRT group (p value > 0.05). The pattern of QoL changes was similar between the VMAT and IMRT group. No statistically or clinically significant difference in all the QoL scales was observed between VMAT and IMRT group at each time point. Compared to before RT, we observed statistically (p
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- 2020
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26. Patients with oral cancer do not undergo surgery as primary treatment: A population-based study in Taiwan
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Cheng-Ping Wang, Li-Jen Liao, Chun-Ju Chiang, Wan-Lun Hsu, Chung-Jan Kang, Chen-Chi Wang, Peir-Rong Chen, Tseng-Cheng Chen, Wen-Wei Huang, and Chih-Yen Chien
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Medicine (General) ,R5-920 - Abstract
Background: There are still oral cancer patients without surgery. To improve the survival, it is necessary to know the causes of the oral cancer patients without surgery. Methods: 23,217 patients with a newly-diagnosed oral cancer in Taiwan Cancer Registry (TCR) database between 2011 and 2015 were enrolled. Data from TCR database named “Reason for No Surgery of Primary Site” were extracted for analysis of the causes of those without surgery. Overall survival plots were presented using the Kaplan–Meier method with log-rank test. Results: 3263 (14%) patients did not received surgery. Among them, there were 720 patients (group 3) without surgery although surgery was advised, 154 patients (group 2) because of poor condition or death before surgery, and 2389 patients (group 1) because of other causes. Twenty-four percent of the patients with surgery were treated one month and more after diagnosis. The 5-year overall survival rates were 68.7%, 25.2%, 9.1% and 17.3% for surgery group, group 3, 2 and 1, respectively (p
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- 2020
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27. Expression of Major Lipid Raft Protein Raftlin in Chronic Rhinosinusitis with Nasal Polyps in Smoking and Non-Smoking Patients Correlated with Interleukin-17 and Tumor Necrosis Factor-α Levels
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Yu-Tsai Lin, Ming-Hsien Tsai, Yan-Ye Su, Wei-Chih Chen, Shun-Chen Huang, and Chih-Yen Chien
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Raftlin ,chronic rhinosinusitis ,nasal polyps ,smoking ,interleukin-17 ,tumor necrosis factor-α ,Microbiology ,QR1-502 - Abstract
Raftlin, as an inflammatory biomarker, has been previously reported in chronic inflammatory diseases. This study investigates the expression of Raftlin in cigarette smokers and in chronic rhinosinusitis with nasal polyps (CRSwNP), as well as evaluating its correlation with interleukin-17 (IL-17) and tumor necrosis factor-α (TNF-α) levels. A total of 30 CRSwNP non-smoking and 16 CRSwNP + SK (smoking) patients undergoing endoscopic sinus surgery were enrolled, while 20 middle turbinate tissue pieces were examined and performed as the control group. In nasal mucosa epithelial staining, Raftlin levels were elevated in the columnar cells and were stained much more intensely in the CRSwNP and CRSwNP + SK groups. Raftlin was located more closely to the apical region of the epithelium in the CRSwNP + SK group; however, the Raftlin levels from whole nasal tissue pieces, according to ELISA data, showed that there was no significant difference between the three different study groups. A positive relationship by Pearson correlation was found between IL-17 or TNF-α levels and Raftlin levels. Taken together, these data indicate that increasing Raftlin expression in columnar cells might involve nasal epithelial remodeling in smokers with CRSwNP.
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- 2022
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28. Prognostic Value of Pathologically Positive Nodal Number in p16-Negative Oropharyngeal and Hypopharyngeal Squamous Cell Carcinoma with pN3b Status
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Ming-Hsien Tsai, Yu-Tsai Lin, Hui-Ching Chuang, Tai-Ling Huang, Hui Lu, Chih-Yen Chien, and Fu-Min Fang
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pathologically positive nodal number ,extranodal extension ,oropharyngeal cancer ,hypopharyngeal cancer ,nomogram ,Medicine (General) ,R5-920 - Abstract
In this study, we aimed to investigate the prognostic value of the number of pathologically positive nodes (pN+) in p16-negative oropharyngeal (OPSCC) and hypopharyngeal (HPSCC) squamous cell carcinoma cases with pN3b status after surgery. We reviewed the clinical and pathological features of 120 newly diagnosed p16-negative OPSCC and HPSCC patients with pN3b status after radical surgery. The primary endpoints were the 5-year overall survival (OS), cancer-specific survival (CSS), and their prognostic factors. We used the Cox proportional hazards model for survival analysis. We generated predictive nomograms that incorporated the clinicopathological factors of OS and CSS. The 5-year OS and CSS rates were 44.1% and 59.1%, respectively. The optimal number of pN+ to predict the 5-year OS and CSS was pN+ = 3. In the Cox model, we observed that pN+ ≥ 3 was a significantly negative predictor of OS (HR: 1.9, 95% CI: 1.1–3.2, p = 0.021) and CSS (HR: 2.3; 95% CI: 1.2–4.6; p = 0.015). After adding the pN+ variable, the c-index of the predictive nomogram incorporating assorted clinicopathological factors increased from 0.66 to 0.689 for OS and from 0.713 to 0.75 for CSS. The results highlight the prognostic value of the pN+ number in p16-negative OPSCC and HPSCC patients with pN3b status.
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- 2022
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29. Angiotensin II receptor blockers and oral squamous cell carcinoma survival: A propensity-score-matched cohort study.
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Ching-Nung Wu, Shao-Chun Wu, Wei-Chih Chen, Yao-Hsu Yang, Jo-Chi Chin, Chih-Yen Chien, Fu-Min Fang, Shau-Hsuan Li, Sheng-Dean Luo, and Tai-Jan Chiu
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Medicine ,Science - Abstract
ObjectivesAngiotensin II receptor blockers (ARBs) improve the survival rates of patients with various cancers. However, it remains unclear whether ARBs confer a survival benefit on patients with oral squamous cell carcinoma (OSCC). Here, we assessed the associations between ARB use and survival in patients with OSCC of different stages.Materials and methodsThis was a 10-year retrospective cohort study of OSCC patients. We enrolled 7,558 patients diagnosed with oral cancer between January 2007 and December 2017 whose details had been entered into the Chang Gung Research Database. Seven hundred and fourteen patients were recruited from the Chang Gung Research Database after performing 1:1 propensity score-matching between ARB users and non-users. Cox's regression models with adjusted covariates were employed to detect factors influencing the survival rates of patients with OSCC.ResultsKaplan-Meier analysis revealed that the overall survival (OS) rate of 180-day ARB users increased (p = 0.038). Cox's regression models indicated that ARB use, younger patients, early-stage OSCC, and patients without diabetes mellitus were independently prognostic of improved OS. Increased OS was more prominent in 180-day ARB users in stage III, Iva, and IVb categories.ConclusionsARB use for more than 180 days is associated with an increased survival rate and is a positive, independent prognostic factor in patients with OSCC. A further two-arm study should be conducted to confirm the clinical usefulness of ARBs in OSCC patients.
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- 2021
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30. Serum Levels of Stromal Cell-Derived Factor-1α and Vascular Endothelial Growth Factor Predict Clinical Outcomes in Head and Neck Squamous Cell Carcinoma Patients Receiving TPF Induction Chemotherapy
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Yen-Hao Chen, Chih-Yen Chien, Yu-Ming Wang, and Shau-Hsuan Li
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SDF-1α ,VEGF ,head and neck cancer ,squamous cell carcinoma ,induction chemotherapy ,TPF ,Biology (General) ,QH301-705.5 - Abstract
Chemokines, such as stromal cell-derived factor-1α (SDF-1α) and vascular endothelial growth factor (VEGF), are associated with clinical outcomes in several cancer types. This study aimed to investigate the role of SDF-1α and VEGF in the prognosis of patients with head and neck squamous cell carcinoma (HNSCC) who underwent TPF induction chemotherapy (docetaxel, cisplatin, and 5-fluorouracil). A total of 77 HNSCC patients were enrolled and circulating SDF-1α and VEGF values were examined at two time points for each patient, including pre-TPF treatment (treatment-naïve) and post-TPF treatment but before chemoradiotherapy. The median progression-free survival (PFS) and overall survival (OS) were 18.1 and 32.9 months, respectively. Decreased SDF-1α and VEGF levels after TPF treatment, post-TPF SDF-1α < 1500 pg/mL and VEGF value < 150 pg/mL were independent prognostic factors for better PFS and OS in univariate and multivariate analyses. A combination of SDF-1α and VEGF values may predict clinical outcomes significantly. Our study confirmed the role of SDF-1α and VEGF in the disease progression of HNSCC, and that decreased SDF-1α and VEGF after TPF treatment and lower post-TPF SDF-1α and VEGF values were associated with better prognosis in HNSCC patients who received induction chemotherapy with TPF followed by chemoradiotherapy.
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- 2022
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31. Radiotherapy Is Associated with an Accelerated Risk of Carotid Atherosclerosis in Patients with Nasopharyngeal Carcinoma: A Nine-Year Prospective Follow-Up Study
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Cheng-Hsien Lu, Yun-Ru Lai, Fu-Min Fang, Teng-Yeow Tan, Wen-Chan Chiu, Dong-Yi Hsieh, Chih-Cheng Huang, Chia-Yi Lien, Ben-Chung Cheng, Chih-Yen Chien, Tai-Lin Huang, and Chia-Te Kung
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atherosclerosis ,inflammation ,nasopharyngeal carcinoma ,oxidative stress and radiotherapy ,platelet activation ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Radiation-related extracranial vasculopathy is a common late effect after radiation in patients with nasopharyngeal carcinoma (NPC). We proposed the hypothesis that radiation-related extracranial vasculopathy is a progressive process that can begin immediately after radiotherapy and persist for a longer period, and inflammation and oxidative stress may play a pivotal role in this process. Thirty-six newly diagnosed NPC patients were assessed with B-mode ultrasound for the common carotid artery (CCA) intima media thickness (IMT) measurement as well as surrogate markers at three different stages (baseline, immediately after concurrent chemoradiation therapy (CCRT), and 9 years after enrollment). A healthy control group was also recruited for comparison. Surrogate markers including a lipid profile, HbA1c, inflammation, oxidative stress, and platelet activation markers were assessed. The mean CCA IMT in the NPC group were increased immediately after CCRT (p = 0.043). The mean CCA IMT value after a 9-year follow-up also showed a significant increase in NPC and control group, respectively (p < 0.0001 and p < 0.0001, paired t test). The annual increase mean CCA IMT (mm) was 0.053 ± 0.025 and 0.014 ± 0.013 in NPC and control group, respectively (p < 0.0001). The baseline high sensitivity CRP (hs-CRP), thiol, TBARS, and CD63 level were significantly higher in the NPC group (hs-CRP, p = 0.001, thiol, p < 0.0001, TBARS, p = 0.05, and CD63 level, p = 0.04). The thiol and TBARS levels were significantly lower in NPC patients immediately after CCRT (thiol, p < 0.0001, and TBARS, p = 0.043). The CD62P level was significantly higher while the thiol level was significantly lower in the NPC group after a 9-year follow-up (CD62P level, p = 0.007; and thiol level, p = 0.004). Radiation-related extracranial vasculopathy is a progressive process that begins immediately after radiotherapy with significantly increased carotid IMT compared to the control group during the 9-year follow-up. Chronic inflammation and oxidative stress might serve to drive the process and also contribute to increased platelet activation.
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- 2022
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32. Comparison of prevalence and associated factors of depressive disorder between patients with head and neck cancer and those with lung cancer at a tertiary hospital in Taiwan: a cross-sectional study
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Chih-Yen Chien, Chin-Chou Wang, Meng-Chih Lin, Yu Lee, Chi-Fa Hung, Pao-Yen Lin, Hung-I Lu, Yung-Che Chen, Mian-Yoon Chong, and Liang-Jen Wang
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Medicine - Abstract
Objective Depression is a common comorbidity in cancer patients. This study aimed to compare the prevalence and associated factors of depressive disorder between patients with head and neck cancer (HNC) and those with lung cancer (LC).Design This study used a cross-sectional design with consecutive sampling.Setting A medical centre (Kaohsiung Chang Gung Memorial Hospital, Taiwan).Participants Patients for the study were recruited from the HNC and LC outpatient clinic and inpatient ward from March 2016 to February 2018. Patients with HNC and LC were enrolled and assessed using the Mini International Neuropsychiatric Interview (MINI).Primary and secondary outcome measures The primary outcome was psychiatric diagnoses assessed using the MINI. The secondary outcomes were psychological well-being assessed using the Beck Anxiety Inventory, Taiwanese Depression Questionnaire, Brief Fatigue Inventory, Numeric Pain Rating Scale and the List of Threatening Experiences Questionnaire.Results In total, 113 HNC patients and 104 LC patients were recruited for the study. The most common psychiatric comorbidity of HNC patients was alcohol use disorder (49.6%), followed by adjustment disorder (20.4%) and depressive disorder (11.5%). The most common psychiatric comorbidity of LC patients was depressive disorder (25.0%), followed by adjustment disorder (17.3%), alcohol use disorder (3.8%) and insomnia disorder (3.8%). Among HNC patients, a self-harm history was positively associated with depression (OR=11.91; 95% CI, 1.47 to 96.83), and a higher educational level was negatively associated with depression (OR=0.77; 95% CI, 0.66 to 0.91). Among LC patients, severity of stressor (OR=2.78; 95% CI, 1.50 to 5.15) and severity of anxiety (OR=1.18; 95% CI, 1.04 to 1.34) were two significant factors associated with depression.Conclusion We reported the prevalence and associated factors of depression between patients with HNC and those with LC. Clinicians should be aware of this comorbidity and the associated risk factors, and conduct intervention programmes to prevent these cancer patients from developing depression.
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- 2020
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33. Predictors of hospital expenses and hospital stay among patients undergoing total laryngectomy: Cost effectiveness analysis.
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Ming-Hsien Tsai, Hui-Ching Chuang, Yu-Tsai Lin, Hui Lu, Fu-Min Fang, Tai-Lin Huang, Tai-Jan Chiu, Shau-Hsuan Li, and Chih-Yen Chien
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Medicine ,Science - Abstract
ObjectiveTo determine the predictive factors of postoperative hospital stay and total hospital medical cost among patients who underwent total laryngectomy.MethodsA total of 213 patients who underwent total laryngectomy in a tertiary referral center for tumor ablation were enrolled retrospectively between January 2009 and May 2018. Statistical analyses including Pearson's chi-squared test were used to determine whether there was a significant difference between each selected clinical factors and outcomes. The outcomes of interest including postoperative length of hospital stay and inpatient total medical cost. Logistic regression analyses were performed to reveal the relationship between clinical factors and postoperative length of hospital stay or total inpatient medical cost.ResultsPreoperative radiotherapy (p = 0.007), method of wound closure (p < 0.001), postoperative serum albumin level (p = 0.025), and postoperative serum hemoglobin level (p = 0.04) were significantly associated with postoperative hospital stay in univariate analysis. Postoperative hypoalbuminemia (odds ratio [OR]: 2.477; 95% confidence interval [CI]: 1.189-5.163; p = 0.015) and previous radiotherapy history (OR 2.194; 95% CI: 1.228-3.917; p = 0.008) are independent predictors of a longer postoperative hospital stay in multiple regression analysis. With respect to total inpatient medical cost, method of wound closure (p < 0.001), preoperative serum albumin level (p = 0.04), postoperative serum albumin level (p < 0.001), and history of liver cirrhosis (p = 0.037) were significantly associated with total inpatient medical cost in univariate analysis. Postoperative hypoalbuminemia (OR: 6.671; 95% CI: 1.927-23.093; p = 0.003) and microvascular free flap reconstruction (OR: 5.011; 95% CI: 1.657-15.156; p = 0.004) were independent predictors of a higher total inpatient medical cost in multiple regression analysis.ConclusionsPostoperative albumin status is a significant factor in predicting prolonged postoperative hospital stay and higher inpatient medical cost among patients who undergo total laryngectomy. In this cohort, the inpatient medical cost was 48% higher and length of stay after surgery was 35% longer among hypoalbuminemia patients.
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- 2020
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34. Adjuvant radiotherapy after curative surgery for oral cavity squamous cell carcinoma and treatment effect of timing and duration on outcome—A Taiwan Cancer Registry national database analysis
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Yung‐Jen Cheng, Mu‐Hung Tsai, Chun‐Ju Chiang, Sen‐Tien Tsai, Tsang‐Wu Liu, Pei‐Jen Lou, Chun‐Ta Liao, Jin‐Ching Lin, Joseph Tung‐Chieh Chang, Ming‐Hsui Tsai, Pen‐Yuan Chu, Yi‐Shing Leu, Kuo‐Yang Tsai, Shyuang‐Der Terng, Chih‐Yen Chien, Muh‐Hwa Yang, Sheng‐Po Hao, Chuan‐Cheng Wang, Ming‐Hsun Tsai, Helen H. W. Chen, Chin Kuo, and Yuan‐Hua Wu
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adjuvant radiotherapy ,cancer database ,oral cancer ,prognostic factor ,treatment time ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Conduct an accurate risk assessment of resected oral cavity squamous cell carcinoma (OSCC) patients by accessing a nationwide systemic investigation is pivotal to improve treatment outcomes. In this article, we tried to determine the impact of different prognostic factors for OSCC patients who received adjuvant radiotherapy (RT) after curative surgery, using Taiwan's national cancer registry database (TCR). A nationwide, large population‐based study was conducted using TCR with patients identified from 2007 to 2015. The study variables included age, gender, cancer subsites, stage, histology grade, margin and extra‐nodal extension (ENE) status, treatment type, surgery to RT interval (ORI), total RT treatment time (RTT), and RT dose. Univariate and multivariate analysis were performed to identify predictors of the variables associated with overall survival (OS), cause‐specific survival (CSS), local‐regional relapse‐free survival (LRFS), and distant metastasis‐free survival (DMFS). 8986 OSCC patients treated with surgery and adjuvant RT were analyzed. In multivariate analysis, worse outcomes were associated with males, older age, subsite in the oral tongue, advanced stage, higher histologic grade, involved margin, and positive ENE. ORI only showed an adverse trend in LRFS, when exceeding 7 weeks (P = .06). RTT >8 weeks was a significant poor predictor in OS, CSS and LRFS (P 70 Gy or ≤50 Gy) also demonstrated an adverse impact on the outcomes. Prolonged RT treatment time and extreme RT doses were identified as significantly poor prognostic predictors in OSCC patients who received adjuvant RT after curative surgery.
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- 2018
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35. Pretreatment prognostic factors of survival and late toxicities for patients with nasopharyngeal carcinoma treated by simultaneous integrated boost intensity-modulated radiotherapy
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Yun-Hsuan Lin, Tai-Lin Huang, Chih-Yen Chien, Hui-Chun Chen, Hsuan-Chih Hsu, Eng-Yen Huang, Chong-Jong Wang, Yu-Jie Huang, Yu-Ming Wang, Chun-Chieh Huang, Shang-Yu Chou, Kuan-Cho Liao, and Fu-Min Fang
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Nasopharyngeal carcinoma ,Simultaneous integrated boost intensity-modulated radiation therapy ,Hematologic inflammatory marker ,Epstein-Barr virus DNA ,Gross tumor volume ,Medical physics. Medical radiology. Nuclear medicine ,R895-920 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background To scrutinize the pretreatment prognosticators on survival and late toxicities in a homogenous cohort of nasopharyngeal carcinoma (NPC) patients treated by simultaneous integrated boost intensity-modulated radiation therapy (SIB-IMRT). Methods A total of 219 non-distant metastatic NPC patients consecutively treated by SIB-IMRT at a single institute were collected. The pretreatment factors including the socio-demographic variables, TNM stages, gross tumor volume (GTV), Epstein-Barr virus (EBV)-DNA, and hematologic inflammatory markers were analyzed. Cox model was used to screen the prognostic factors of late toxicities and four survival outcomes including locoregional relapse-free survival (LRRFS), distant metastasis-free survival (DMFS), failure-free survival (FFS), and overall survival (OS). Results Statistically significant inter-correlations were observed between the values of EBV-DNA, some hematologic inflammatory markers, GTV, and N classification. The 5-year LRRFS, DMFS, FFS, and OS rates were 87.9%, 89.4%, 79.4%, and 81.3%, respectively. Multivariate analysis revealed that advanced N classification (N2–3 vs. N0–1) remained the only significant negative prognosticator for all the four survival outcomes. An increased monocyte percentage and a decreased lymphocyte-to-monocyte ratio were significantly associated with poorer FFS and OS, respectively. Larger GTV was observed to be predictive of poorer LRRFS. Patients with T3–4 (HR: 3.5, 95% CI: 1.0–12.1, p = 0.048) or higher GTV (HR: 1.006, 95% CI: 1.001–1.011, p = 0.027) were associated with higher incidence of radiation neuropathy. Conclusion N classification remains the most significant survival predictor for NPC patients treated by SIB-IMRT after adjusting these biomarkers. GTV impacts not only on locoregional control but also radiation neuropathy.
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- 2018
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36. Quality of Life as a Mediator between Cancer Stage and Long-Term Mortality in Nasopharyngeal Cancer Patients Treated with Intensity-Modulated Radiotherapy
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Kuan-Cho Liao, Hui-Ching Chuang, Chih-Yen Chien, Yu-Tsai Lin, Ming-Hsien Tsai, Yan-Ye Su, Chao-Hui Yang, Chi-Chih Lai, Tai-Lin Huang, Shau-Hsuan Li, Tsair-Fwu Lee, Wei-Ting Lin, Chien-Hung Lee, and Fu-Min Fang
- Subjects
quality of life ,mediator ,nasopharyngeal carcinoma ,intensity modulated radiotherapy ,mortality ,Baron and Kenny’s method ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background: Quality of life (QoL) attained before, during, or after treatments is recognized as a vital factor associated with therapeutic benefits in cancer patients. This nasopharyngeal cancer (NPC) patient longitudinal study assessed the relationship among QoL, cancer stage, and long-term mortality in patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT). Patients and Methods: The European Organization for Research and Treatment of Cancer (EORTC) core QoL questionnaire (QLQ-C30) and the head and neck cancer-specific QoL questionnaire module (QLQ-HN35) were employed to evaluate four-dimensional QoL outcomes at five time points: pre- (n = 682), during (around 40 Gy) (n = 675), 3 months (n = 640), 1 year (n = 578) and 2 years post-IMRT (n = 505), respectively, for 682 newly diagnosed NPC patients treated between 2003 and 2017 at a single institute. The median followed-up time was 7.5 years, ranging from 0.3 to 16.1 years. Generalized estimating equations, multivariable proportional hazards models, and Baron and Kenny’s method were used to assess the investigated effects. Results: Advanced AJCC stage (III–IV) patients revealed a 2.26-fold (95% CI—1.56 to 3.27) higher covariate-adjusted mortality risk than early-stage (I–II) patients. Compared with during IMRT, advanced-stage patients had a significantly low global health QoL and a significantly high QoL-HN35 symptom by a large magnitude at pre-, 3 months, and 2 years post-IMRT. QoL scales at pre-IMRT, 1 year, and 2 years post-IMRT were significantly associated with mortality. The effect changes of mortality risk explained by global health QoL, QoL-C30, and QoL-HN35 symptom were 5.8–9.8% at pre-IMRT but at 2 years post-IMRT were 39.4–49.4% by global health QoL and QoL-HN35 symptoms. Conclusions: We concluded advanced cancer stage correlates with a long-term high mortality in NPC patients treated with IMRT and the association is partially intermediated by QoL at pre-IMRT and 2 years post-IMRT. Therefore, QoL-HN35 symptom and global health QoL-dependent medical support and care should be focused and tailored at 2 years post-IMRT.
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- 2021
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37. Ribophorin II Overexpression Is Associated with Poor Response to Induction Chemotherapy with Docetaxel, Cisplatin, and Fluorouracil in P16-Negative Locally Advanced Head and Neck Squamous Cell Carcinoma
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Wei-Shan Chen, Sheng-Dean Luo, Tai-Jan Chiu, Yu-Ming Wang, Wei-Chih Chen, Chih-Yen Chien, Fu-Min Fang, Tai-Lin Huang, and Shau-Hsuan Li
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head and neck cancer ,ribophorin II (RPN2) ,induction chemotherapy ,Medicine - Abstract
This study aims to evaluate the relationship between human ribophorin II (RPN2) and the effect of treatment using induction therapy with docetaxel, cisplatin, and fluorouracil (TPF) for p-16 negative locally advanced head and neck squamous cell carcinoma (HNSCC). A total of 203 patients with locally advanced p-16 negative HNSCC who received induction chemotherapy with TPF at the Kaohsiung Chang Gung Memorial Hospital between 2009 and 2014 were enrolled. Immunohistochemistry (IHC) for RPN2 was examined and correlated with treatment outcome. Our study showed that RPN2 overexpression was significantly correlated with a poor response to induction chemotherapy with TPF. Both RPN2 overexpression and clinical N1 to N3 stages represented adverse prognostic factors for progression-free survival (PFS) and overall survival (OS). RPN2 might be a predictive marker for treatment response to induction chemotherapy. Further clinical trials are needed to determine the therapeutic significance of RPN2 in patients with HNSCC.
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- 2021
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38. JAK2 Phosphorylation Signals and Their Associated Cytokines Involved in Chronic Rhinosinusitis with Nasal Polyps and Correlated with Disease Severity
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Yu-Tsai Lin, Wei-Chih Chen, Ming-Hsien Tsai, Jing-Ying Chen, Chih-Yen Chien, and Shun-Chen Huang
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chronic rhinosinusitis ,nasal polyps ,p-JAK2 ,p-STAT ,disease severity ,Microbiology ,QR1-502 - Abstract
Janus kinase 2 (JAK2) is a member of the JAK family that transduces cytokine-mediated signals via the JAKs/STATs (signal transducer and activator of transcription proteins) pathway, which plays an important role in many inflammatory diseases. This study investigates the association of p-JAK2 and JAK2-associated cytokines from nasal polyp (NP) tissue with disease severity, and evaluates the p-JAK2-mediated STATs in chronic rhinosinusitis (CRS) with NP. Sixty-one CRSwNP patients with nasal polyps undergoing endoscopic sinus surgery were enrolled, while the turbinate tissues from 26 nasal obstruction patients were examined as the control group. Elevated levels of p-JAK2 were detected in CRSwNP, and significantly correlated with scores of disease severity (LMK-CT, TPS, and SNOT-22). Expressions of the JAK2-associated cytokines, such as IL-5, IL-6, IL-13, G-CSF, and IFN-γ were significantly higher in CRSwNP than in the controls, while the levels of IL-5, IL-6, IL-13, or G-CSF had positive correlation with scores of disease severity. Moreover, markedly increased expression of p-STAT3 in CRSwNP was observed relative to the control. Taken together, these data showed that the JAK2-associated cytokines including IL-6 and G-CSF may stimulate JAK2 phosphorylation to activate p-STAT3, indicating an association with disease severity and supporting its development of JAK2 inhibitor as a potential therapeutic agent for CRS.
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- 2021
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39. Prognostic significance and function of mammalian target of rapamycin in tongue squamous cell carcinoma
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Shau-Hsuan Li, Chih-Yen Chien, Wan-Ting Huang, Sheng-Dean Luo, Yan-Ye Su, Wan-Yu Tien, Ya-Chun Lan, and Chang-Han Chen
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Medicine ,Science - Abstract
Abstract Despite improvement in preoperative imaging, surgical technique, and adjuvant therapy, the prognosis of patients with tongue squamous cell carcinoma (SCC) is still unsatisfactory. The mammalian target of rapamycin (mTOR) play a key role in the regulation of tumor cell proliferation and survival. However, the significance of mTOR on the prognosis of tongue SCC remains largely undefined. In the present study, immunohistochemistry was performed to evaluate the expression of phosphorylated mTOR (p-mTOR) in 160 surgically resected tongue SCC, and correlated with survival. Univariate analysis revealed that p-mTOR overexpression (P = 0.006) was associated with inferior overall survival. In multivariate comparison, p-mTOR overexpression (P = 0.002, hazard ratio = 2.082) remained independently associated with worse overall survival. In vitro study, tongue cancer cells treated with everolimus, the specific mTOR inhibitor, or transfected with mTOR-mediated siRNAs dramatically attenuated the abilities of cell proliferation by MTT and BrdU assays. In 4-NQO-induced tongue cancer murine model, mTOR inhibitors significantly decreased the incidence of tongue SCC. In conclusion, p-mTOR overexpression was independently associated with poor prognosis of patients with tongue SCC. In vitro and vivo, mTOR inhibition showed the promising activity in tongue SCC. Our results suggest that inhibition of mTOR signaling pathway may be a novel therapeutic target for tongue SCC.
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- 2017
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40. Metformin disrupts malignant behavior of oral squamous cell carcinoma via a novel signaling involving Late SV40 factor/Aurora-A
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Chang-Han Chen, Hsin-Ting Tsai, Hui-Ching Chuang, Li-Yen Shiu, Li-Jen Su, Tai-Jan Chiu, Sheng-Dean Luo, Fu-Min Fang, Chao-Cheng Huang, and Chih-Yen Chien
- Subjects
Medicine ,Science - Abstract
Abstract Conventional therapeutic processes in patient with OSCC are associated with several unfavorable effects leading to patients with poor survival rate. Metformin has been shown to protect against a variety of specific diseases, including cancer. However, the precise roles and mechanisms underlying the therapeutic effects of metformin on OSCC remain elusive. In the current study, in vitro and xenograft model experiments revealed that metformin inhibited growth and metastasis of oral cancer cells. Importantly, metformin-restrained tumorigenesis of oral cancer was accompanied with strong decrease of both Aurora-A and Late SV40 Factor (LSF) expressions. Furthermore, LSF contributed to Aurora-A-elicited malignancy behaviors of oral cancer via binding to the promoter region of Aurora-A. A significant correlation was observed between LSF and Aurora-A levels in a cohort of specimens of oral cancer. These findings showed that a novel LSF/Aurora-A-signaling inhibition supports the rationale of using metformin as potential OSCC therapeutics.
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- 2017
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41. Targeting mTOR-CCL20 Signaling May Improve Response to Docetaxel in Head and Neck Squamous Cell Carcinoma
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Ming-Huei Chou, Hui-Ching Chuang, Yu-Tsai Lin, Ming-Hsien Tsai, Ying-Hsien Kao, I-Chun Lin, Tai-Lin Huang, Fu-Min Fang, and Chih-Yen Chien
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head and neck squamous cell carcinoma ,mTOR-CCL-20 ,docetaxel ,rapamycin ,BEZ235 ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Patients with advanced head and neck squamous cell carcinoma (HNSCC) usually show a dismal prognosis. It is this worthwhile to develop new, effective therapeutic regimens for these patients, such as molecular targeted therapy, which is promising as an alternative or combination treatment for HNSCC. The mammalian target of rapamycin (mTOR) pathway, which plays an important role in the carcinogenesis of HNSCC, is the most frequently activated, and is thus worthy of further investigation. In this study, two human HNSCC cell lines, FaDu and SAS, were evaluated for cell growth with trypan blue staining and tumor growth using an orthotopic xenograft model. The immunohistochemical expression of mTOR in the subcutaneous xenograft model and the inhibitory effects of docetaxel on the growth and state of activation of the PI3K/mTOR pathway were also evaluated and examined by colony formation and Western blot, respectively. Cell proliferation and migration were measured by water-soluble tetrazolium salt (WST-1) and OrisTM cell migration assay, respectively. Furthermore, the effects of rapamycin and BEZ235, a phosphatidylinositol 3-kinases (PI3K) and mTOR inhibitor in combination with docetaxel or CCL20 were evaluated in the FaDu and SAS cells. The results showed that the expression of mTOR was significantly higher in the SAS and FaDu xenograft models than in the control. Docetaxel treatment significantly suppressed HNSCC cell proliferation and migration in vitro via the PI3K/mTOR/CCL-20 signaling pathway. Additionally, when administered in a dose-dependent fashion, mTOR inhibitors inhibited the growth and migration of the HNSCC cells. This combination was synergistic with docetaxel, resulting in almost complete cell growth and migration arrest. In conclusion, docetaxel significantly inhibited HNSCC cell proliferation and migration in vitro via the PI3K/mTOR/CCL-20 signaling pathway. The synergistic and additive activity of mTOR inhibitors combined with docetaxel shows potential as a new treatment strategy for HNSCC.
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- 2021
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42. Verification of Saliva Matrix Metalloproteinase-1 as a Strong Diagnostic Marker of Oral Cavity Cancer
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Ya-Ting Chang, Lichieh Julie Chu, Yen-Chun Liu, Chih-Jou Chen, Shu-Fang Wu, Chien-Hua Chen, Ian Yi-Feng Chang, Jun-Sheng Wang, Tzong-Yuan Wu, Srinivas Dash, Wei-Fan Chiang, Sheng-Fu Chiu, Shin-Bin Gou, Chih-Yen Chien, Kai-Ping Chang, and Jau-Song Yu
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oral cancer ,saliva ,biomarker ,MMP-1 ,ELISA ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Oral squamous cell carcinoma (OSCC) accounts for >90% of cases of oral cancer, including cancer at the lip and oral cavity and cancer at the oropharynx. Most OSCCs develop from oral potentially malignant disorders (OPMDs), which consist of heterogeneous lesions with different malignant transformation potentials that make early detection of OSCC a challenge. Using a targeted mass spectrometry-based assay to compare multiple candidate proteins, we previously identified matrix metalloproteinase-1 (MMP-1) as one of the most promising salivary OSCC biomarkers. To explore the clinical utility of MMP-1 in OSCC detection, we developed an in-house, sensitive enzyme-linked immunosorbent assay (ELISA) for measuring MMP-1 content, and tested it on saliva samples from 1160 subjects (313 healthy controls, and 578 OPMD and 269 OSCC patients) collected at two medical centers. Salivary MMP-1 levels measured by our in-house ELISA significantly discriminated OSCC patients from non-cancerous groups. A receiver operating characteristic curve analysis showed that MMP-1 was effective in separating non-cancer groups from patients with OSCCs at the oral cavity. Additionally, salivary MMP-1 levels in oral cavity cancer patients were highly correlated with tumor progression (tumor size, lymph node metastasis, and overall stage). Collectively, our results indicate that salivary MMP-1 is an effective biomarker for OSCC that can be sensitively detected using our newly developed ELISA. The newly developed MMP-1 ELISA may be used as a new adjunctive tool to aid in detecting and monitoring OSCC.
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- 2020
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43. Efficacy of Different Chemotherapy Regimens in Patients with Locally Advanced Synchronous Esophageal and Head/Neck Squamous Cell Carcinoma Receiving Curative Concurrent Chemoradiotherapy
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Yen-Hao Chen, Hung-I Lu, Chih-Yen Chien, Chien-Ming Lo, Yu-Ming Wang, Shang-Yu Chou, and Shau-Hsuan Li
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chemotherapy ,synchronous ,head and neck cancer ,esophageal cancer ,concurrent chemoradiotherapy ,Medicine - Abstract
Esophageal squamous cell carcinoma (ESCC) and head/neck squamous cell carcinoma (HNSCC) are very common cancers worldwide, and there is higher incidence of synchronous ESCC/NSCC in Taiwan. The aim of the current study was to investigate the efficacy of different chemotherapy regimens in patients with locally advanced synchronous ESCC/HNSCC who received curative concurrent chemoradiotheapy (CCRT). A total of 75 patients were identified and assigned to one of two groups: 45 patients receiving cisplatin/5-fluorouracil (5-FU) regime in one group and 30 patients receiving a weekly cisplatin regime in the other. Overall survival (OS) was calculated from the date of diagnosis of the ESCC or HNSCC to the date of death from any cause or the most recent follow-up. Kaplan−Meier curves and log-rank tests were used to estimate OS and differences between the two groups, respectively. There was no significant difference in the analysis of OS between the cisplatin/5-FU and the weekly cisplatin groups. However, patients that interrupted their CCRT were found to have worse OS compared to those without interruptions (5.4 months versus 18.8 months, p = 0.002). In subgroup analysis, patients without interruptions of CCRT had a better OS than those with interruptions in the cisplatin/5-FU group (13.0 months versus 5.4 months, p = 0.041) as well as in the weekly cisplatin group (21.4 months versus 5.0 months, p = 0.017). Interruption of CCRT was the only independently poor prognostic factor of OS in the univariate and multivariate (hazard ratio 0.18, p < 0.001) analyses. Most interruption of CCRT resulted from adverse events (AEs) or serious AEs. Although there was no significant difference in the incidence of AEs between these two groups, lower incidence of adverse events was mentioned in the weekly cisplatin group. Our study suggests that interruption of CCRT is an independently poor prognostic factor of OS, and that completion of CCRT without interruption is more important than the choice of chemotherapeutic regimen for patients with synchronous ESCC/HNSCC.
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- 2020
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44. Clinical impact of albumin in advanced head and neck cancer patients with free flap reconstruction—a retrospective study
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Ming-Hsien Tsai, Hui-Ching Chuang, Yu-Tsai Lin, Hui Lu, Wei-Chih Chen, Fu-Min Fang, and Chih-Yen Chien
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Hypoalbuminemia ,Nutritional status ,Reconstruction ,Wound infection ,Hospital stay ,Prognostic factor ,Medicine ,Biology (General) ,QH301-705.5 - Abstract
Background Poor nutritional status among patients with advanced stage head and neck squamous cell carcinoma (HNSCC) is common. Albumin is a common indicator of nutritional status and has been shown to be a predictor of oncological outcomes and perioperative morbidity. This study aims to determine the prognostic value of the serum albumin level among patients with advanced HNSCC undergoing surgery with simultaneous free flap reconstruction. Methods A total of 233 patients with advanced head and neck cancer undergoing tumor resection and immediate microvascular free flap reconstruction in a tertiary referral center were enrolled retrospectively between January 2009 and December 2011. Statistical analyses including Pearson’s chi-squared test were used to determine whether there was a significant difference between each selected clinical factors and postoperative major wound infection. Multiple regression analysis was performed to reveal the relationship between postoperative major wound infection and clinical factors. Kaplan–Meier curves and multivariate Cox regression were applied to analyse survival outcome for overall survival (OS), disease-specific survival (DSS) and disease-free survival (DFS). Results Postoperative serum albumin level (p
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- 2018
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45. Ethanolic Extracts of Pluchea indica Induce Apoptosis and Antiproliferation Effects in Human Nasopharyngeal Carcinoma Cells
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Chiu-Li Kao, Joshua Cho, Ya-Zhe Lee, Yuan-Bin Cheng, Chih-Yen Chien, Chung-Feng Hwang, Yi-Ren Hong, Chao-Neng Tseng, and Chung-Lung Cho
- Subjects
Pluchea indica ,nasopharyngeal carcinoma (NPC) ,p53 ,apoptosis ,Organic chemistry ,QD241-441 - Abstract
Pluchea indica is used in traditional medicine for the treatment of lumbago, ulcer, tuberculosis and inflammation. The anti-cancer activities and the underlying molecular mechanisms of the ethanolic extracts of P. indica root (PIRE) were characterized in the present study. PIRE strongly inhibited the viability of the human nasopharyngeal carcinoma cells (NPC-TW 01 and NPC-TW 04) in a time- and dose-dependent manner. Migration of cancer cells was also suppressed by PIRE. In addition, PIRE significantly increased the occurrence of the cells in sub-G1 phase and the extent of DNA fragmentation in a dose-dependent manner, which indicates that PIRE significantly increased apoptosis in NPC cells. The apoptotic process triggered by PIRE involved up-regulation of pro-apoptotic Bax protein and down-regulation of anti-apoptotic Bcl-2 protein, consequently increasing the ratios of Bax/Bcl-2 protein levels. Moreover, the p53 protein was up-regulated by PIRE in a concentration-dependent manner. Therefore, PIRE could induce the apoptosis-signaling pathway in NPC cells by activation of p53 and by regulation of apoptosis-related proteins.
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- 2015
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46. Clinical impact of human papillomavirus in laryngeal squamous cell carcinoma: a retrospective study
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Wei-Chih Chen, Hui-Ching Chuang, Yu-Tsai Lin, Chao-Cheng Huang, and Chih-Yen Chien
- Subjects
HPV ,Laryngeal cancer ,Survival ,Recurrence ,Prevalence ,Medicine ,Biology (General) ,QH301-705.5 - Abstract
Objectives The purpose of this study is to determine the prevalence and clinical impact of human papillomavirus (HPV) related laryngeal squamous cell carcinoma (LSCC). Methods A total of 106 LSCC patients who underwent primary surgical resection with or without adjuvant radiotherapy/chemoradiotherapy were enrolled retrospectively. Tumors collected from paraffin-embedded samples were used for HPV detection by polymerase chain reaction and in situ hybridization technique. Clinicopathological parameters were recorded for analysis. Results The prevalence of HPV in patients with LSCC was 13.2% in our series and 12 out of 14 (85.7%) HPV-positive tumors were HPV-16. The patients with HPV-positive tumors were older (p = 0.042), less local/regional recurrence (p = 0.037) and non-smoker (p = 0.068). There was no significant difference in the 5-year overall survival (OS) (p = 0.8056) between HPV-positive and -negative tumors. The patients with HPV-positive tumors had a better 5-year disease-specific survival (DSS) (100% vs. 84.8%, p = 0.1485), although the difference did not reach statistical significance. However, the local/regional control rate was significantly better in HPV-positive tumors than in HPV-negative tumors (100% vs. 75%, p = 0.0494). Conclusions A low prevalence of HPV infection in our series suggests that HPV is not a major cause of LSCC. However, a 100% local/regional control rate and DSS were observed in HPV-positive tumors. This finding suggests a different tumor behavior between HPV-positive and HPV-negative LSCC. Further research with a larger sample size is necessary to confirm our observations.
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- 2017
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47. Mortality in tongue cancer patients treated by curative surgery: a retrospective cohort study from CGRD
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Ming-Shao Tsai, Chia-Hsuan Lai, Chuan-Pin Lee, Yao-Hsu Yang, Pau-Chung Chen, Chung-Jan Kang, Geng-He Chang, Yao-Te Tsai, Chang-Hsien Lu, Chih-Yen Chien, Chi-Kuang Young, Ku-Hao Fang, Chin-Jui Liu, Re-Ming A. Yeh, and Wen-Cheng Chen
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Prognosis ,Risk factors ,Oral cancer ,Oral cavity ,Survival ,CGRD (Chang Gung Research Database) ,Medicine ,Biology (General) ,QH301-705.5 - Abstract
Background Our study aimed to compare the outcomes of surgical treatment of tongue cancer patients in three different age groups. Methods From 2004 to 2013, we retrospectively analyzed the clinical data of 1,712 patients who were treated in the four institutions constituting the Chang Gung Memorial Hospitals (CGMH). We divided and studied the patients in three age groups: Group 1, younger (
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- 2016
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48. Nox4 Overexpression as a Poor Prognostic Factor in Patients with Oral Tongue Squamous Cell Carcinoma Receiving Surgical Resection
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Yen-Hao Chen, Chih-Yen Chien, Fu-Min Fang, Tai-Lin Huang, Yan-Ye Su, Sheng-Dean Luo, Chao-Cheng Huang, Wei-Che Lin, and Shau-Hsuan Li
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Nox4 ,oral tongue cancer ,squamous cell carcinoma ,surgery ,Medicine - Abstract
Background: Nox4 has been reported to promote tumor progression of various types of cancer through many different pathways. The current study was designed to evaluate the prognostic significance of Nox4 in patients with oral tongue squamous cell carcinoma (OTSCC) receiving surgical resection. Methods: We retrospectively analyzed the 161 patients with OTSCC treated with surgical resection, including 81 patients with high expression of Nox4 and 80 patients with low expression of Nox4. Two OTSCC cell lines, SAS and SCC4, were used to investigate the proliferation activity. Results: The univariate and multivariable analyses showed that negative nodal metastasis and low expression of Nox4 were significantly associated with superior disease-free survival (DFS) and overall survival (OS). Western blotting analysis indicated that Nox4 was highly expressed in these two OTSCC cell lines and knockdown of Nox4 was successful by transfecting with Nox4 shRNA. In addition, these cell lines were also treated with a Nox4 inhibitor (GKT-137831) and the results showed GKT-137831 could inhibit the proliferation of OTSCC tumor cells in a dose-dependent manner. Conclusion: Our study suggests that Nox4 plays an important role in disease progression of OTSCC and Nox4 overexpression is a poor prognostic factor for patients with OTSCC who received surgical resection.
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- 2018
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49. Characterization of the Targeting Accuracy of a Neuronavigation-Guided Transcranial FUS System In Vitro, In Vivo, and In Silico.
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Lu Xu, Christopher P. Pacia, Yan Gong, Zhongtao Hu, Chih-Yen Chien, Leqi Yang, H. Michael Gach, Yao Hao, Hassanzadeh Comron, Jiayi Huang, Eric C. Leuthardt, and Hong Chen
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- 2023
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50. Extraction of Ruler Markings For Estimating Physical Size of Oral Lesions.
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Zhiyun Xue, Kelly Yu, Paul C. Pearlman, Tseng-Cheng Chen, Chun-Hung Hua, Chung Jan Kang, Chih-Yen Chien, Ming-Hsui Tsai, Cheng-Ping Wang, Anil K. Chaturvedi, and Sameer K. Antani
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- 2022
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