26 results on '"Hsin Lun Lee"'
Search Results
2. NEDD8 promotes radioresistance via triggering autophagy formation and serves as a novel prognostic marker in oral squamous cell carcinoma
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Tsu-Zong Yuan, Hui-Yu Lin, Chia-Hao Kuei, Che-Hsuan Lin, Hsun-Hua Lee, Hsin-Lun Lee, Hsiao-Wei Lu, Chia-Yi Su, Hui-Wen Chiu, and Yuan-Feng Lin
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Cancer Research ,Oncology ,Genetics - Abstract
Background Radiotherapy is the first-line regimen for treating oral squamous cell carcinoma (OSCC) in current clinics. However, the development of therapeutic resistance impacts the anticancer efficacy of irradiation in a subpopulation of OSCC patients. As a result, discovering a valuable biomarker to predict radiotherapeutic effectiveness and uncovering the molecular mechanism for radioresistance are clinical issues in OSCC. Methods Three OSCC cohorts from The Cancer Genome Atlas (TCGA), GSE42743 dataset and Taipei Medical University Biobank were enrolled to examine the transcriptional levels and prognostic significance of neuronal precursor cell-expressed developmentally downregulated protein 8 (NEDD8). Gene set enrichment analysis (GSEA) was utilized to predict the critical pathways underlying radioresistance in OSCC. The colony-forming assay was used to estimate the consequences of irradiation sensitivity after the inhibition or activation of the NEDD8-autophagy axis in OSCC cells. Results NEDD8 upregulation was extensively found in primary tumors compared to normal adjacent tissues and potentially served as a predictive marker for the therapeutic effectiveness of irradiation in OSCC patients. NEDD8 knockdown enhanced radiosensitivity but NEDD8 overexpression reduced it in OSCC cell lines. The inclusion of MLN4924, a pharmaceutical inhibitor for NEDD8-activating enzyme, dose-dependently restored the cellular sensitivity to irradiation treatment in irradiation-insensitive OSCC cells. Computational simulation by GSEA software and cell-based analyses revealed that NEDD8 upregulation suppresses Akt/mTOR activity to initiate autophagy formation and ultimately confers radioresistance to OSCC cells. Conclusion These findings not only identify NEDD8 as a valuable biomarker to predict the efficacy of irradiation but also offer a novel strategy to overcome radioresistance via targeting NEDD8-mediated protein neddylation in OSCC.
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- 2023
3. Outcomes of intracranial germinoma—A retrospective multinational Asian study on effect of clinical presentation and differential treatment strategies
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Kyung-Nam Koh, Ru Xin Wong, Dong-Eun Lee, Jung Woo Han, Hwa Kyung Byun, Hong In Yoon, Dong-Seok Kim, Chuhl Joo Lyu, Hyoung Jin Kang, Kyung Taek Hong, Joo Ho Lee, Il Han Kim, Ji Hoon Phi, Seung-Ki Kim, Tai-Tong Wong, Hsin-Lun Lee, I-Chun Lai, Yu-Mei Kang, Young-Shin Ra, Seung Do Ahn, Ho Joon Im, Wen Shen Looi, Sharon Yin Yee Low, Enrica Ee Kar Tan, Hyun Jin Park, Sang Hoon Shin, Hiroshi Fuji, Chang-Ok Suh, Yi-Wei Chen, and Joo-Young Kim
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Salvage Therapy ,Cancer Research ,Oncology ,Brain Neoplasms ,Clinical Investigations ,Humans ,Germinoma ,Neurology (clinical) ,Pineal Gland ,Retrospective Studies - Abstract
Background This multinational study was conducted to report clinical presentations and treatment strategies in patients with intracranial germinomas across selected Asian centers, including failure patterns, risk factors, and outcomes. Methods A retrospective data collection and analysis of these patients, treated between 1995 and 2015 from eight healthcare institutions across four countries was undertaken. Results From the results, 418 patients were analyzed, with a median follow-up of 8.9 years; 79.9% of the patients were M0, and 87.6% had β-human chorionic gonadotropin values Conclusions Survival outcomes of patients with germinoma were excellent. Thus, the focus of treatment for intracranial germinoma should be on survivorship. Further studies are warranted to find the optimal intensity and volume of radiation, including the role of chemotherapy in the survival of patients with intracranial germinomas, considering age, primary tumor location, and extent of disease.
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- 2021
4. Outcomes of intracranial non-germinomatous germ cell tumors: a retrospective Asian multinational study on treatment strategies and prognostic factors
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Kyung Taek Hong, Jung Woo Han, Hiroshi Fuji, Hwa Kyung Byun, Kyung-Nam Koh, Ru Xin Wong, Hsin-Lun Lee, Hong In Yoon, Joo Ho Lee, Ji Hoon Phi, Seung-Ki Kim, Dong-Seok Kim, Chuhl Joo Lyu, Jung Yoon Choi, Hyoung Jin Kang, Yi-Wei Chen, Yi-Yen Lee, Ho Joon Im, Young-Shin Ra, Seung Do Ahn, Sharon Yin Yee Low, Wen Shen Looi, Hyeon Jin Park, Yang-Gun Suh, Chang-Ok Suh, Kyu-Chang Wang, Enrica Ee Kar Tan, Tai-Tong Wong, and Joo-Young Kim
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Male ,Cancer Research ,Neurology ,Oncology ,Brain Neoplasms ,Humans ,Chorionic Gonadotropin, beta Subunit, Human ,Neurology (clinical) ,Germinoma ,Neoplasms, Germ Cell and Embryonal ,Child ,Prognosis ,Retrospective Studies - Abstract
Non-germinomatous germ cell tumors (NGGCTs) are rare pediatric conditions. This multicenter study using Asian multinational patient data investigated treatment outcomes and prognostic factors for NGGCTs.Medical records of 251 patients with NGGCTs treated from 1995 to 2015 were retrospectively analyzed from participating centers in Asian countries (Korea, Taiwan, Singapore, and Japan).The median follow up was 8.5 years (95% CI 7.8-9.9). In the total cohort, 5-year event-free survival (EFS) and overall survival (OS) rates were 78.2% and 85.4%, respectively. In 17.9% of the patients, diagnosis was determined by tumor markers alone (alpha-fetoprotein ≥ 10 ng/mL (Korea) or 25 ng/mL (Taiwan and Singapore), and/or β-human chorionic gonadotropin (β-hCG) ≥ 50 mIU/mL). Patients with immature teratomas and mature teratomas comprised 12.0% and 8.4%, respectively. The 5-year EFS rate was higher in patients with histologically confirmed germinoma with elevated β-hCG (n = 28) than those in patients with malignant NGGCTs (n = 127). Among malignant NGGCTs, patients with choriocarcinoma showed the highest 5-year OS of 87.6%, while yolk sac tumors showed the lowest OS (68.8%). For malignant NGGCT subgroups, an increase in serum β-hCG levels by 100 mIU/mL was identified as a significant prognostic factor associated with the EFS and OS.Our result shows excellent survival outcomes of overall CNS NGGCT. However, treatment outcome varied widely across the histopathologic subgroup of NGGCT. Hence, this study suggests the necessity for accurate diagnosis by surgical biopsy and further optimization of diagnosis and treatment according to the histopathology of NGGCTs. Future clinical trials should be designed for individualized treatments for different NGGCTs subsets.
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- 2022
5. Pretreatment Neutrophil-to-Lymphocyte Ratio Predicts Survival and Liver Toxicity in Patients With Hepatocellular Carcinoma Treated With Stereotactic Ablative Radiation Therapy
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Chun Shu Lin, Jeng Fong Chiou, Po Chien Shen, Yang Hong Dai, Wei Chou Chang, Shang Wen Chen, Chun You Chen, Jen Fu Yang, Wen Yen Huang, Jason Chia-Hsien Cheng, Hsin Lun Lee, Cheng-Hsiang Lo, Chih Weim Hsiang, and Meei-Shyuan Lee
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Cancer Research ,medicine.medical_specialty ,Radiation ,Receiver operating characteristic ,business.industry ,medicine.medical_treatment ,fungi ,Area under the curve ,Retrospective cohort study ,SABR volatility model ,medicine.disease ,Gastroenterology ,Confidence interval ,030218 nuclear medicine & medical imaging ,Radiation therapy ,03 medical and health sciences ,0302 clinical medicine ,Oncology ,030220 oncology & carcinogenesis ,Internal medicine ,Hepatocellular carcinoma ,medicine ,Radiology, Nuclear Medicine and imaging ,Neutrophil to lymphocyte ratio ,business - Abstract
PURPOSE The objective of this study was to determine whether pretreatment neutrophil-to-lymphocyte ratio (NLR) could predict survival outcomes and liver toxicity in hepatocellular carcinoma (HCC) patients treated with stereotactic ablative radiation therapy (SABR). METHODS AND MATERIALS In this retrospective study we collected pretreatment NLR of HCC patients treated with SABR between December 2007 and August 2018 and determined its association with overall survival (OS), progression-free survival, and radiation-related liver toxicity defined as an increase in the Child-Turcotte-Pugh score by ≥2 within 3 months after SABR in the absence of disease progression. RESULTS A total of 153 patients with a median follow-up of 13.3 months were included. Receiver operating characteristic curve analysis found that an NLR ≥2.4 was optimum (area under the curve, 0.762; 95% confidence interval [CI], 0.682-0.841, P < .001) for predicting poor 1-year OS (38.2% vs 83.6%, P < .001). Multivariable analysis demonstrated that NLR was significantly associated with OS, both as a continuous (P = .006) and a binary variable (NLR set at 2.4; P = .003). Multiple tumors (P = .003), macrovascular invasion (P = .024), extrahepatic spread (P = .002), and albumin-bilirubin score (P = .020) were also significant predictors of OS. Elevated NLR independently prognosticated poor progression-free survival (P = .016). Liver toxicity was seen in 22 evaluable patients (15.4%). Receiver operating characteristic curve analysis found NLR ≥4.0 was optimum at predicting liver toxicity (31.4% vs 10.2%, P = .005). A higher NLR (P = .049) and albumin-bilirubin score (P = .002) were independent risk factors for liver toxicity. CONCLUSIONS NLR is an objective and ubiquitous inflammatory marker that can predict OS and liver toxicity in HCC patients undergoing SABR. NLR could be a useful biomarker for patient risk stratification and therapeutic decision-making.
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- 2021
6. Loco-regional deep hyperthermia combined with intravesical Mitomycin instillation reduces the recurrence of non-muscle invasive papillary bladder cancer
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Syuan-Hao Syu, Liang-Ming Lee, Yung-Wei Lin, Benjamin Chung Howe Lai, Hung-Jen Shih, Ke-Hsun Lin, Yu-Ching Wen, Hsin-Lun Lee, and Yen-Chun Fan
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Hyperthermia ,Cancer Research ,medicine.medical_specialty ,recurrence ,Physiology ,Mitomycin ,Urology ,thermal dose ,Physiology (medical) ,Medical technology ,medicine ,Humans ,R855-855.5 ,Adverse effect ,Survival rate ,Antibiotics, Antineoplastic ,Bladder cancer ,business.industry ,Therapeutic effect ,Hyperthermia Treatment ,Hyperthermia, Induced ,hyperthermia ,medicine.disease ,Administration, Intravesical ,Urinary Bladder Neoplasms ,bladder cancer ,Neoplasm Recurrence, Local ,Thermal dose ,Non muscle invasive ,business - Abstract
Objectives To compare the therapeutic effects of locoregional deep hyperthermia combined with intravesical chemotherapy with those of intravesical chemotherapy alone in patients with intermediate-/high-risk non-muscle invasive bladder cancer (NMIBC). To evaluate the impact of thermal dose in hyperthermia treatment. Methods We analyzed data retrieved from the medical records of patients with intermediate-/high-risk NMIBC treated with intravesical mitomycin (IM group) or locoregional deep hyperthermia combined with intravesical mitomycin (CHT group) at a single tertiary care hospital between May 2016 and June 2019. The primary and secondary endpoints were the recurrence-free survival rate and progression-free survival rate, respectively. Thermal dose was evaluated and adverse events were also recorded. Results In total, 43 patients (CHT: 18 patients, IM: 25 patients) were enrolled. The median follow-up durations were 14 and 23 months, respectively. The recurrence rate at 12 months was significantly lower in the CHT group than in the IM group (11.1% vs. 44%, p = .048); this trend persisted at 24 months (CHT: 11.1%, IM: 48%; p = .027). The recurrence-free survival was also significantly higher in the CHT group than in the IM group (p = .028). No tumor recurrence was noted in patients who received a thermal dose of ≥4 CEM43. All adverse events were well tolerated, and there was no treatment-related mortality. Conclusions Intravesical chemotherapy combined with locoregional deep hyperthermia for intermediate-/high-risk papillary NMIBC can significantly decrease the recurrence rate relative to that observed after intravesical chemotherapy alone.
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- 2021
7. Atypical Teratoid/Rhabdoid Tumor in Taiwan: A Nationwide, Population-Based Study
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Yen-Lin Liu, Min-Lan Tsai, Chang-I Chen, Noi Yar, Ching-Wen Tsai, Hsin-Lun Lee, Chia-Chun Kuo, Wan-Ling Ho, Kevin Li-Chun Hsieh, Sung-Hui Tseng, James S. Miser, Chia-Yau Chang, Hsi Chang, Wen-Chang Huang, Tai-Tong Wong, Alexander T. H. Wu, and Yu-Chun Yen
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Cancer Research ,survival outcome ,atypical teratoid/rhabdoid tumor ,CNS tumors ,pediatric cancer ,Oncology ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background: Atypical teratoid/rhabdoid tumor (AT/RT) is a rare, highly aggressive embryonal brain tumor most commonly presenting in young children. Methods: We performed a nationwide, population-based study of AT/RT (ICD-O-3 code: 9508/3) in Taiwan using the Taiwan Cancer Registry Database and the National Death Certificate Database. Results: A total of 47 cases (male/female = 29:18; median age at diagnosis, 23.3 months (IQR: 12.5–87.9)) were diagnosed with AT/RT between 1999 and 2014. AT/RT had higher prevalence in males (61.70%), in children < 36 months (55.32%), and at infratentorial or spinal locations (46.81%). Survival analyses demonstrated that patients ≥ 3 years of age (n = 21 (45%)) had a 5y-OS of 41% (p < 0.0001), treatment with radiotherapy only (n = 5 (11%)) led to a 5y-OS of 60%, treatment with chemotherapy with or without radiotherapy (n = 27 (62%)) was associated with a 5y-OS of 45% (p < 0.0001), and patients with a supratentorial tumor (n = 11 (23%)) had a 5y-OS of 51.95%. Predictors of better survival on univariate Cox proportional hazard modeling and confirmed with multivariate analysis included older age (≥1 year), supratentorial sites, and the administration of radiotherapy, chemotherapy, or both. Gender had no effect on survival. Conclusion: Older age, supratentorial site, and treatment with radiotherapy, chemotherapy, or both significantly improves the survival of patients with AT/RT.
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- 2022
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8. Molecularly Targeted Photothermal Ablation of Epidermal Growth Factor Receptor-Expressing Cancer Cells with a Polypyrrole–Iron Oxide–Afatinib Nanocomposite
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Lekshmi Rethi, Chinmaya Mutalik, Lekha Rethi, Wei-Hung Chiang, Hsin-Lun Lee, Wen-Yu Pan, Tze-Sen Yang, Jeng-Fong Chiou, Yin-Ju Chen, Er-Yuan Chuang, and Long-Sheng Lu
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polypyrrole ,iron oxide ,afatinib ,EGFR ,photothermal therapy ,Cancer Research ,Oncology - Abstract
Near-infrared–photothermal therapy (NIR-PTT) is a potential modality for cancer treatment. Directing photothermal effects specifically to cancer cells may enhance the therapeutic index for the best treatment outcome. While epithelial growth factor receptor (EGFR) is commonly overexpressed/genetically altered in human malignancy, it remains unknown whether targeting EGFR with tyrosine kinase inhibitor (TKI)-conjugated nanoparticles may direct NIR-PTT to cancers with cellular precision. In the present study, we tested this possibility through the fabrication of a polypyrrole–iron oxide–afatinib nanocomposite (PIA-NC). In the PIA-NC, a biocompatible and photothermally conductive polymer (polypyrrole) was conjugated to a TKI (afatinib) that binds to overexpressed wild-type EGFR without overt cytotoxicity. A Fenton catalyst (iron oxide) was further encapsulated in the NC to drive the intracellular ROS surge upon heat activation. Diverse physical and chemical characterization experiments were conducted. Particle internalization, cytotoxicity, ROS production, and apoptosis in EGFR-positive and -negative cell lines were investigated in the presence and absence of NIR. We found that the PIA-NCs were stable with a size of 243 nm and a zeta potential of +35 mV. These PIA-NCs were readily internalized close to the cell membrane by all types of cells used in the study. The Fourier transform infrared spectra showed 3295 cm−1 peaks; substantial O–H stretching was seen, with significant C=C stretching at 1637 cm−1; and a modest appearance of C–O–H bending at 1444 cm−1 confirmed the chemical conjugation of afatinib but not iron oxide to the NC. At a NIR-PTT energy level that has a minimal cytotoxic effect, PIA-NC significantly sensitizes EGFR-overexpressing A549 lung cancer cells to NIR-PTT-induced cytotoxicity at a rate of 70%, but in EGFR-negative 3T3 fibroblasts the rate was 30%. Within 1 min of NIR-PTT, a surge of intracellular ROS was found in PIA-NC-treated A549 cells. This was followed by early induction of cellular apoptosis for 54 ± 0.081% of A549 cells. The number of viable cells was less than a quarter of a percent. Viability levels of A549 cells that had been treated with NIR or PIA were only 50 ± 0.216% and 80 ± 0.216%, respectively. Only 10 ± 0.816% of NIH3T3 cells had undergone necrosis, meaning that 90 ± 0.124% were alive. Viability levels were 65 ± 0.081% and 81 ± 0.2%, respectively, when only NIR and PIA were used. PIA binding was effective against A549 cells but not against NIH3T3 cells. The outcome revealed that higher levels of NC + NIR exposure caused cancer cells to produce more ROS. In summary, our findings proved that a molecularly targeted NC provides an orchestrated platform for cancer cell-specific delivery of NIR-PTT. The geometric proximity design indicates a novel approach to minimizing the off-target biological effects of NIR-PTT. The potential of PIA-NC to be further developed into real-world application warrants further investigation.
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- 2022
9. Molecular Mechanisms of Chemotherapy Resistance in Head and Neck Cancers
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Yuzuka Kanno, Chang-Yu Chen, Hsin-Lun Lee, Jeng-Fong Chiou, and Yin-Ju Chen
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Cancer Research ,chemotherapy resistance ,Combination therapy ,medicine.medical_treatment ,Review ,chemotherapy ,combination therapy ,chemistry.chemical_compound ,Medicine ,Epidermal growth factor receptor ,RC254-282 ,Cisplatin ,Chemotherapy ,biology ,business.industry ,Head and neck cancer ,Cancer ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,Oncology ,Docetaxel ,Paclitaxel ,chemistry ,Cancer research ,biology.protein ,head and neck cancer ,immunotherapy ,business ,medicine.drug - Abstract
Chemotherapy resistance is a huge barrier for head and neck cancer (HNC) patients and therefore requires close attention to understand its underlay mechanisms for effective strategies. In this review, we first summarize the molecular mechanisms of chemotherapy resistance that occur during the treatment with cisplatin, 5-fluorouracil, and docetaxel/paclitaxel, including DNA/RNA damage repair, drug efflux, apoptosis inhibition, and epidermal growth factor receptor/focal adhesion kinase/nuclear factor-κB activation. Next, we describe the potential approaches to combining conventional therapies with previous cancer treatments such as immunotherapy, which may improve the treatment outcomes and prolong the survival of HNC patients. Overall, by parsing the reported molecular mechanisms of chemotherapy resistance within HNC patient’s tumors, we can improve the prediction of chemotherapeutic responsiveness, and reveal new therapeutic targets for the future.
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- 2021
10. A Combined Systemic Strategy for Overcoming Cisplatin Resistance in Head and Neck Cancer: From Target Identification to Drug Discovery
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Ann-Joy Cheng, Long Sheng Lu, Chang Yu Chen, Yuzuka Kanno, Meng Yu Lai, Lai Lei Ting, Jeng Fong Chiou, Hsin Lun Lee, Guo Rung You, and Yin Ju Chen
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0301 basic medicine ,Cancer Research ,SPC25 ,lcsh:RC254-282 ,Article ,Transcriptome ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,medicine ,Gene silencing ,Viability assay ,celastrol ,Cisplatin ,mitotic division ,biology ,Chemistry ,Cancer ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,030104 developmental biology ,Oncology ,Cell culture ,Celastrol ,030220 oncology & carcinogenesis ,Cancer research ,biology.protein ,head and neck cancer ,cisplatin resistance ,transcriptome ,medicine.drug ,RHEB - Abstract
Cisplatin is the first-line chemotherapy agent for head and neck cancer (HNC), but its therapeutic effects are hampered by its resistance. In this study, we employed systemic strategies to overcome cisplatin resistance (CR) in HNC. CR cells derived from isogenic HNC cell lines were generated. The CR related hub genes, functional mechanisms, and the sensitizing candidates were globally investigated by transcriptomic and bioinformatic analyses. Clinically, the prognostic significance was assessed by the Kaplan&ndash, Meier method. Cellular and molecular techniques, including cell viability assay, tumorsphere formation assay, RT-qPCR, and immunoblot, were used. Results showed that these CR cells possessed highly invasive and stem-like properties. A total of 647 molecules was identified, and the mitotic division exhibited a novel functional mechanism significantly related to CR. A panel of signature molecules, MSRB3, RHEB, ULBP1, and spindle pole body component 25 (SPC25), was found to correlate with poor prognosis in HNC patients. SPC25 was further shown as a prominent molecule, which markedly suppressed cancer stemness and attenuated CR after silencing. Celastrol, a nature extract compound, was demonstrated to effectively inhibit SPC25 expression and reverse CR phenotype. In conclusion, the development of SPC25 inhibitors, such as the application of celastrol, maybe a novel strategy to sensitize cisplatin for the treatment of refractory HNC.
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- 2020
11. A Few-Shot Learning Approach Assists in the Prognosis Prediction of Magnetic Resonance-Guided Focused Ultrasound for the Local Control of Bone Metastatic Lesions
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Fang-Chi Hsu, Hsin-Lun Lee, Yin-Ju Chen, Yao-An Shen, Yi-Chieh Tsai, Meng-Huang Wu, Chia-Chun Kuo, Long-Sheng Lu, Shauh-Der Yeh, Wen-Sheng Huang, Chia-Ning Shen, and Jeng-Fong Chiou
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Cancer Research ,machine learning ,Oncology ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,magnetic resonance-guided focused ultrasound surgery ,HIFU ,prognosis prediction ,RC254-282 ,Article ,bone metastasis - Abstract
Simple Summary We report a local control prediction model for patients undergoing MRgFUS ablation, and provide promising guidance for clinicians to identify a suitable treatment strategy for bone metastatic lesions. We propose a few-shot learning approach to establish the quick prediction of clinical and radiographic responses. On the basis of demographic data, pre-/post-treatment immune-related cytokine change, and MRI imaging, the most suitable parameters were selected to assess potential treatment outcomes during the acute inflammatory stages within 24 h. Traditional logistic regression and few-shot learning models were compared to identify the best model on an independent test. The best predictive few-shot learning model (accuracy of 85.2%, sensitivity of 88.6%, and AUC of 0.95) was achieved by combining the clinical features with the levels of significant cytokines IL-6, IL-13, IP-10, and eotaxin. Abstract Magnetic resonance-guided focused ultrasound surgery (MRgFUS) constitutes a noninvasive treatment strategy to ablate deep-seated bone metastases. However, limited evidence suggests that, although cytokines are influenced by thermal necrosis, there is still no cytokine threshold for clinical responses. A prediction model to approximate the postablation immune status on the basis of circulating cytokine activation is thus needed. IL-6 and IP-10, which are proinflammatory cytokines, decreased significantly during the acute phase. Wound-healing cytokines such as VEGF and PDGF increased after ablation, but the increase was not statistically significant. In this phase, IL-6, IL-13, IP-10, and eotaxin expression levels diminished the ongoing inflammatory progression in the treated sites. These cytokine changes also correlated with the response rate of primary tumor control after acute periods. The few-shot learning algorithm was applied to test the correlation between cytokine levels and local control (p = 0.036). The best-fitted model included IL-6, IL-13, IP-10, and eotaxin as cytokine parameters from the few-shot selection, and had an accuracy of 85.2%, sensitivity of 88.6%, and AUC of 0.95. The acceptable usage of this model may help predict the acute-phase prognosis of a patient with painful bone metastasis who underwent local MRgFUS. The application of machine learning in bone metastasis is equivalent or better than the current logistic regression.
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- 2022
12. Upregulation of Protein Synthesis and Proteasome Degradation Confers Sensitivity to Proteasome Inhibitor Bortezomib in Myc-Atypical Teratoid/Rhabdoid Tumors
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Yun Ru Liu, Feng Chi Chang, Muh Lii Liang, Shih-Chieh Lin, Wen Chang Huang, Tsung Han Hsieh, Donald Ming-Tak Ho, Kevin Li Chun Hsieh, Hsin Hung Chen, Meng En Chao, Huy Minh Tran, Yi Yen Lee, Yen Lin Liu, Wan Chen, Chun A. Changou, Che Chang Chang, Min Lan Tsai, Shian Ying Sung, Tai-Tong Wong, Kuo Sheng Wu, Hsin Lun Lee, Alice L. Yu, Yun Yen, and Shing Shung Chu
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0301 basic medicine ,p53 ,Cancer Research ,protein synthesis ,Oncology and Carcinogenesis ,lcsh:RC254-282 ,Article ,03 medical and health sciences ,Rare Diseases ,0302 clinical medicine ,Downregulation and upregulation ,Gene expression ,Genetics ,medicine ,2.1 Biological and endogenous factors ,Aetiology ,Multiple myeloma ,Cancer ,Pediatric ,Oncogene ,Chemistry ,Bortezomib ,bortezomib ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,proteasome degradation ,Orphan Drug ,030104 developmental biology ,Oncology ,5.1 Pharmaceuticals ,Apoptosis ,Cell culture ,030220 oncology & carcinogenesis ,Proteasome inhibitor ,Cancer research ,Myc-ATRTs ,Development of treatments and therapeutic interventions ,Biotechnology ,medicine.drug - Abstract
Atypical teratoid rhabdoid tumors (ATRTs) are among the most malignant brain tumors in early childhood and remain incurable. Myc-ATRT is driven by the Myc oncogene, which directly controls the intracellular protein synthesis rate. Proteasome inhibitor bortezomib (BTZ) was approved by the Food and Drug Administration as a primary treatment for multiple myeloma. This study aimed to determine whether the upregulation of protein synthesis and proteasome degradation in Myc-ATRTs increases tumor cell sensitivity to BTZ. We performed differential gene expression and gene set enrichment analysis on matched primary and recurrent patient-derived xenograft (PDX) samples from an infant with ATRT. Concomitant upregulation of the Myc pathway, protein synthesis and proteasome degradation were identified in recurrent ATRTs. Additionally, we found the proteasome-encoding genes were highly expressed in ATRTs compared with in normal brain tissues, correlated with the malignancy of tumor cells and were essential for tumor cell survival. BTZ inhibited proliferation and induced apoptosis through the accumulation of p53 in three human Myc-ATRT cell lines (PDX-derived tumor cell line Re1-P6, BT-12 and CHLA-266). Furthermore, BTZ inhibited tumor growth and prolonged survival in Myc-ATRT orthotopic xenograft mice. Our findings suggest that BTZ may be a promising targeted therapy for Myc-ATRTs.
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- 2020
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13. Ex Vivo Expanded Circulating Tumor Cells for Clinical Anti-Cancer Drug Prediction in Patients with Head and Neck Cancer
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Kuan-Chou Lin, Peng-Yuan Wang, Ching-Zong Wu, Chang-Yu Chen, Kai-Chiang Yang, Hsin-Lun Lee, Dennis-Chun-Yu Ho, Fang-Chi Hsu, Lai-Lei Ting, Thierry Burnouf, Jeng-Fong Chiou, Chia-Lun Chang, Chu-Huang Chen, Yin Ju Chen, and Long Sheng Lu
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Oncology ,Drug ,Cancer Research ,medicine.medical_specialty ,media_common.quotation_subject ,medicine.medical_treatment ,circulating tumor cells ,Article ,Circulating tumor cell ,response to therapy ,Internal medicine ,medicine ,In patient ,Ex vivo expansion ,drug sensitivity ,RC254-282 ,media_common ,Cisplatin ,Chemotherapy ,business.industry ,ex vivo expansion ,head and neck cancer ,Head and neck cancer ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,business ,Ex vivo ,medicine.drug - Abstract
Simple Summary The conventional methods that seek to predict clinical treatment response are based on the number of circulating tumor cells (CTCs) present in liquid biopsies or genetic profiling of extracted CTCs. This paper presents a novel process by which CTCs can be extracted from blood samples taken from head and neck cancer patients and then expanded ex vivo to form organoids that can be tested with a panel of anti-cancer treatments. The resulting drug sensitivity profiles derived from cisplatin treatment of organoids were subsequently found to correlate with clinical treatment response to cisplatin in patients. CTCs extracted from liquid biopsies for ex vivo expansion negates the need for complicated and potentially risky biopsies of tumor material, thereby supporting the application of this procedure for checkups and treatment monitoring. Abstract The advanced-stage head and neck cancer (HNC) patients respond poorly to platinum-based treatments. Thus, a reliable pretreatment method for evaluating platinum treatment response would improve therapeutic efficiency and outcomes. This study describes a novel strategy to predict clinical drug responses in HNC patients by using eSelect, a lab-developed biomimetic cell culture system, which enables us to perform ex vivo expansion and drug sensitivity profiling of circulating tumor cells (CTCs). Forty liquid biopsies were collected from HNC patients, and the CTCs were expanded ex vivo using the eSelect system within four weeks. Immunofluorescence staining confirmed that the CTC-derived organoids were positive for EpCAM and negative for CD45. Two illustrative cases present the potential of this strategy for evaluating treatment response. The statistical analysis confirmed that drug sensitivity in CTC-derived organoids was associated with a clinical response. The multivariant logistic regression model predicted that the treatment accuracy of chemotherapy responses achieved 93.75%, and the area under the curves (AUCs) of prediction models was 0.8841 in the whole dataset and 0.9167 in cisplatin specific dataset. In summary, cisplatin sensitivity profiles of patient-derived CTCs expanded ex vivo correlate with a clinical response to cisplatin treatment, and this can potentially underpin predictive assays to guide HNC treatments.
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- 2021
14. Prognostic and predictive factors for clinical and radiographic responses in patients with painful bone metastasis treated with magnetic resonance-guided focused ultrasound surgery
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Kevin Li Chun Hsieh, Yu Ching Wen, Chia Chun Kuo, Yi Chieh Tsai, Jo Ting Tsai, Jeng Fong Chiou, Meng Huang Wu, Hsiao Wei Yu, Hsin Lun Lee, Fang Chi Hsu, and Chun You Chen
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Adult ,Male ,Cancer Research ,medicine.medical_specialty ,lcsh:Medical technology ,Physiology ,medicine.medical_treatment ,Bone Neoplasms ,Logistic regression ,030218 nuclear medicine & medical imaging ,Lesion ,thermal ablation ,03 medical and health sciences ,0302 clinical medicine ,bone metastases ,Physiology (medical) ,Medicine ,Humans ,Aged ,Retrospective Studies ,Performance status ,business.industry ,mrgfus ,Bone metastasis ,Retrospective cohort study ,Odds ratio ,Middle Aged ,medicine.disease ,Prognosis ,Magnetic Resonance Imaging ,High-intensity focused ultrasound ,Confidence interval ,lcsh:R855-855.5 ,pain palliation ,030220 oncology & carcinogenesis ,high intensity focused ultrasound ,High-Intensity Focused Ultrasound Ablation ,Female ,Radiology ,medicine.symptom ,business ,prediction and monitoring of tumor response - Abstract
Background: Magnetic resonance-guided focused ultrasound surgery (MRgFUS) is an alternative local therapy for patients with painful bone metastasis. However, little is known about the prognostic and predictive factors of MRgFUS in treating bone metastasis. Materials and methods: This retrospective study analyzed the performance status, treated site, pretreatment pain score, pretreatment tumor volume and lesion coverage volume factor (CVF) of 31 patients who underwent MRgFUS. A numerical rating scale for pain was used at the same time to assess the clinical response. Radiographic responses were evaluated using a modified version of The University of Texas MD Anderson Cancer Center criteria and reference to the MR imaging or computed tomography scans obtained 3 months after treatment. Univariate and multivariate logistic regression analyses were conducted to examine the effect of variables on clinical and radiographic responses. Results: The overall clinical response rate was 83.9% and radiographic response rate was 67.7%. Multivariate logistic regression analysis revealed that the better pretreatment Karnofsky performance status (KPS) (odds ratio: 1.220, 95% confidence interval (CI): 1.033–1.440; p = 0.019) was significantly associated with a more positive clinical response, and that the lesion CVF (odds ratio: 1.183, 95% CI: 1.029–1.183; p = 0.0055) was an independent prognostic factor for radiographic responses. The radiographic response of patients with lesion CVF ≥70% and CVF
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- 2019
15. RARE-45. SARCOMAS INVOLVING THE CENTRAL NERVOUS SYSTEM AT INITIAL PRESENTATION IN CHILDREN AND YOUNG ADULTS: A CASE SERIES
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Sung-Hui Tseng, Chia-Yau Chang, Kevin Li Chun Hsieh, Yu-Chien Kao, Tai-Tong Wong, Jia-Hui Huang, Shu-Huey Chen, Shu-Mei Chen, Yen Lin Liu, Hsi Chang, Jinn-Li Wang, Hsin-Lun Lee, Min-Lan Tsai, and James S. Miser
- Subjects
Cancer Research ,Series (stratigraphy) ,Pediatrics ,medicine.medical_specialty ,business.industry ,Central nervous system ,medicine.anatomical_structure ,Oncology ,medicine ,AcademicSubjects/MED00300 ,AcademicSubjects/MED00310 ,Neurology (clinical) ,Presentation (obstetrics) ,Young adult ,business ,Craniopharyngioma and Rare Tumors - Abstract
Sarcomas of bone, soft tissue, or neural origin may occasionally invade the central nervous system (CNS), causing diagnostic and therapeutic challenges. We aim to investigate the clinical features of sarcomas involving the CNS at initial presentation. During 2015/01–2019/12, nine consecutive patients (4 Males and 5 Females) younger than 30 years of age treated at a University Healthcare System in Northern Taiwan were included. The median age was 8.7 years (range, 2–24 years); diagnoses were Ewing Sarcoma with EWSR1 rearrangements (n=4), CIC-NUTM1 Sarcoma (n=1), Osteosarcoma (n=2), Malignant Peripheral Nerve Sheath Tumor (MPNST; n=1), and extramedullary myeloid sarcoma (n=1). The tumors originated from the skull (n=1), dura (n=1), vertebra (n=4), spinal canal (n=1), or extra-CNS sites (n=2). Four patients had metastases (1 Ewing sarcoma, 2 osteosarcoma, and 1 extramedullary myeloid sarcoma). The main symptom at diagnosis was facial/eye pain (n=2), back pain (n=3), arm weakness (n=1), or gait disturbance (n=3). Upfront neurosurgical decompression (n=7) or urgent radiotherapy (n=1) was performed in most patients. At a median follow-up duration of 20.1 months, the overall survival rate was 70%. All patients with Ewing sarcoma (n=4) and CIC-NUTM1 sarcoma (n=1) achieved Complete Response after surgery, interval-compressed chemotherapy, radiotherapy, and adjuvant chemotherapy. Patients with stage IV osteosarcoma (n=2) had Partial Response; the patients with MPNST and extraskeletal myeloid sarcoma died of Progressive Disease at 18 and 3 months after diagnosis, respectively. We conclude that timely decompression, early diagnosis, and histology-driven multimodality treatment are effective strategies in managing sarcomas involving the CNS.
- Published
- 2020
16. Ex Vivo Expansion and Drug Sensitivity Profiling of Circulating Tumor Cells from Patients with Small Cell Lung Cancer
- Author
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Peng-Yuan Wang, Chia-Ning Shen, Her Shyong Shiah, Jeng Fong Chiou, Kai Ling Lee, Chi Li Chung, Thierry Burnouf, Lai Lei Ting, Han Lin Hsu, Yin Ju Chen, Pai Chien Chou, Hsin Lun Lee, Long Sheng Lu, and Yen Lin Liu
- Subjects
0301 basic medicine ,Drug ,Cancer Research ,media_common.quotation_subject ,Drug resistance ,circulating tumor cells ,Immunofluorescence ,lcsh:RC254-282 ,Article ,03 medical and health sciences ,0302 clinical medicine ,Circulating tumor cell ,medicine ,Liquid biopsy ,Etoposide ,media_common ,Cisplatin ,liquid biopsy ,medicine.diagnostic_test ,business.industry ,personalized medicine ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,small cell lung cancer ,business ,Ex vivo ,primary cell culture ,medicine.drug - Abstract
Small cell lung cancer (SCLC) represents one of the most aggressive malignancies among cancer types. Not only tumor sample availability is limited, but also the ability for tumor cells to rapidly acquire drug resistance are the rate-limiting bottlenecks for overall survival in current clinical settings. A liquid biopsy capable of capturing and enriching circulating tumor cells (CTCs), together with the possibility of drug screening, is a promising solution. Here, we illustrate the development of a highly efficient ex vivo CTC expansion system based on binary colloidal crystals substrate. Clinical samples were enrolled from 22 patients with SCLC in the study. The CTCs were enriched and expanded from the collected peripheral blood samples. Expanded cells were analyzed for protein expression and observed for drug sensitivity with the use of immunofluorescence and ATP titer evaluation, respectively. Successful CTC spheroid proliferation was established after 4 weeks within 82% of all the collected peripheral blood samples from enrolled patients. Upon immunofluorescence analysis, the enriched cells showed positive markers for EpCAM, TTF-1, synaptophysin and negative for CD45. Additionally, the expanded CTCs demonstrated marked heterogeneity in the expression of E-cadherin and N-cadherin. In a preliminary case series, the drug sensitivity of patient-derived CTC to cisplatin and etoposide was studied to see the correlation with the corresponding therapeutic outcome. In conclusion, our study demonstrates that it is possible to efficiently expand CTCs from SCLC within a clinically relevant time frame, the biomarker information generated from enriched CTCs can assist the selection of effective drugs and improve disease outcome.
- Published
- 2020
17. Molecular-Clinical Correlation in Pediatric Medulloblastoma: A Cohort Series Study of 52 Cases in Taiwan
- Author
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Shing Shung Chu, Muh Lii Liang, Yi Yen Lee, Feng Chi Chang, Wen Chang Huang, Che Chang Chang, Huy Minh Tran, Tai-Tong Wong, Yun Ru Liu, Er Chieh Cho, Yen Lin Liu, Wan Chen, Hsin Hung Chen, Shih-Chieh Lin, Kuo Sheng Wu, Meng En Chao, Donald Ming-Tak Ho, Alice L. Yu, Tsung Han Hsieh, Chun A. Changou, Min Lan Tsai, Shian Ying Sung, Kevin Li Chun Hsieh, Hsin Lun Lee, Shiann-Tarng Jou, Kung Hao Liang, and Yi Wei Chen
- Subjects
0301 basic medicine ,Oncology ,Cancer Research ,risk stratification ,DNA damage response ,Metastasis ,0302 clinical medicine ,2.1 Biological and endogenous factors ,RNA-Seq ,Aetiology ,Exome sequencing ,Cancer ,Pediatric ,screening and diagnosis ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Detection ,030220 oncology & carcinogenesis ,Cohort ,DNA methylation ,Pediatric Research Initiative ,medicine.medical_specialty ,Pediatric Cancer ,Oncology and Carcinogenesis ,medulloblastoma ,lcsh:RC254-282 ,Article ,03 medical and health sciences ,Rare Diseases ,Germline mutation ,Clinical Research ,Internal medicine ,Genetics ,molecular-clinical correlation ,medicine ,Genetic predisposition ,Genetic Testing ,Gene ,Medulloblastoma ,business.industry ,Human Genome ,medicine.disease ,Brain Disorders ,4.1 Discovery and preclinical testing of markers and technologies ,Brain Cancer ,Good Health and Well Being ,molecular–clinical correlation ,030104 developmental biology ,somatic mutations ,business ,genetic predisposition - Abstract
In 2016, a project was initiated in Taiwan to adopt molecular diagnosis of childhood medulloblastoma (MB). In this study, we aimed to identify a molecular-clinical correlation and somatic mutation for exploring risk-adapted treatment, drug targets, and potential genetic predisposition. In total, 52 frozen tumor tissues of childhood MBs were collected. RNA sequencing (RNA-Seq) and DNA methylation array data were generated. Molecular subgrouping and clinical correlation analysis were performed. An adjusted Heidelberg risk stratification scheme was defined for updated clinical risk stratification. We selected 51 genes for somatic variant calling using RNA-Seq data. Relevant clinical findings were defined. Potential drug targets and genetic predispositions were explored. Four core molecular subgroups (WNT, SHH, Group 3, and Group 4) were identified. Genetic backgrounds of metastasis at diagnosis and extent of tumor resection were observed. The adjusted Heidelberg scheme showed its applicability. Potential drug targets were detected in the pathways of DNA damage response. Among the 10 patients with SHH MBs analyzed using whole exome sequencing studies, five patients exhibited potential genetic predispositions and four patients had relevant germline mutations. The findings of this study provide valuable information for updated risk adapted treatment and personalized care of childhood MBs in our cohort series and in Taiwan.
- Published
- 2020
18. Stereotactic Body Radiation Therapy Versus Conventional Radiotherapy for Hepatic Metastasis from Colorectal Carcinoma
- Author
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J.F. Chiou, Chia-Chun Kuo, Hsin-Lun Lee, Yao-Ru Huang, and W.J. Wang
- Subjects
Cancer Research ,medicine.medical_specialty ,Radiation ,business.industry ,Stereotactic body radiation therapy ,Colorectal cancer ,medicine.disease ,Hepatic metastasis ,Conventional radiotherapy ,Oncology ,Medicine ,Radiology, Nuclear Medicine and imaging ,Radiology ,business - Published
- 2019
19. Sarcopenia is Associated with Inferior Response to Neoadjuvant Chemoradiation in Patients with Locally Advanced Rectal Cancer
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J.F. Chiou, L.J. Kuo, Y. Huang, L.S. Lu, J.Y. Wu, Chia-Chun Kuo, Hsin-Lun Lee, C.J. Cheng, and Lai-Lei Ting
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Radiation ,business.industry ,Colorectal cancer ,Locally advanced ,medicine.disease ,Internal medicine ,Sarcopenia ,medicine ,Radiology, Nuclear Medicine and imaging ,In patient ,business - Published
- 2018
20. Epigenetic Modification and Differentiation Induction of Malignant Glioma Cells by Oligo-Fucoidan
- Author
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Chien-Huang Liao, Shuang-En Chuang, Chih-Jung Yao, Hui-Ching Kuo, Hsin-Lun Lee, Jacqueline Whang-Peng, I-Chun Lai, and Gi-Ming Lai
- Subjects
Methyltransferase ,differentiation induction ,Pharmaceutical Science ,Decitabine ,Antineoplastic Agents ,Article ,Epigenesis, Genetic ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Polysaccharides ,oligo-fucoidan ,Cell Line, Tumor ,epigenetic modification ,Glioma ,Drug Discovery ,Biomarkers, Tumor ,medicine ,Humans ,Epigenetics ,lcsh:QH301-705.5 ,Pharmacology, Toxicology and Pharmaceutics (miscellaneous) ,030304 developmental biology ,0303 health sciences ,biology ,Brain Neoplasms ,Cell Differentiation ,DNA methyltransferases ,malignant glioma ,Methylation ,medicine.disease ,Gene Expression Regulation, Neoplastic ,medicine.anatomical_structure ,lcsh:Biology (General) ,chemistry ,030220 oncology & carcinogenesis ,Cancer research ,biology.protein ,Neoplasm Recurrence, Local ,Growth inhibition ,NeuN ,Glioblastoma ,medicine.drug ,Astrocyte - Abstract
Malignant glioma (MG) is a poor prognostic brain tumor with inevitable recurrence after multimodality treatment. Searching for more effective treatment is urgently needed. Differentiation induction via epigenetic modification has been proposed as a potential anticancer strategy. Natural products are known as fruitful sources of epigenetic modifiers with wide safety margins. We thus explored the effects of oligo-fucoidan (OF) from brown seaweed on this notion in MG cells including Grade III U87MG cells and Grade IV glioblastoma multiforme (GBM)8401 cells and compared to the immortalized astrocyte SVGp12 cells. The results showed that OF markedly suppress the proliferation of MG cells and only slightly affected that of SVGp12 cells. OF inhibited the protein expressions of DNA methyltransferases 1, 3A and 3B (DNMT1, 3A and 3B) accompanied with obvious mRNA induction of differentiation markers (MBP, OLIG2, S100&beta, GFAP, NeuN and MAP2) both in U87MG and GBM8401 cells. Accordingly, the methylation of p21, a DNMT3B target gene, was decreased by OF. In combination with the clinical DNMT inhibitor decitabine, OF could synergize the growth inhibition and MBP induction in U87MG cells. Appropriated clinical trials are warranted to evaluate this potential complementary approach for MG therapy after confirmation of the effects in vivo.
- Published
- 2019
21. Histological subtype and smoking status, but not gender, are associated with epidermal growth factor receptor mutations in non-small-cell lung cancer
- Author
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Sey-En Lin, Ling Ling Chiang, Jinn-Li Wang, Cheng-Wen Wu, Chia-Lang Fang, Chi-Li Chung, Shih-Hsin Hsiao, H. Eugene Liu, Ming-Chih Yu, Yu-Ting Chou, and Hsin-Lun Lee
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,biology ,business.industry ,Confounding ,Cancer ,Odds ratio ,medicine.disease ,Bioinformatics ,medicine.disease_cause ,respiratory tract diseases ,Internal medicine ,biology.protein ,medicine ,Adenocarcinoma ,Epidermal growth factor receptor ,Lung cancer ,business ,Carcinogenesis ,EGFR inhibitors - Abstract
Mutations in epidermal growth factor receptor (EGFR) commonly occur in non-small-cell lung cancer (NSCLC) patients characterized by female gender, never-smoker status and adenocarcinoma histology. The aim of this study was to determine whether gender is a confounding factor for EGFR mutations in NSCLC. To elucidate the confounding effect, Pearson's χ2 test and logistic regression models were used to correlate these characteristics with EGFR mutations in 426 NSCLC patients treated at our institutes. Of those 426 NSCLC patients, 47% were females, 57% were non-smokers and 84% had adenocarcinomas. The multivariate logistic regression analysis demonstrated that never-smoker status [odds ratio (OR)=3.49, 95% confidence interval (CI): 1.99-6.13; P
- Published
- 2013
22. Chinese Herbal Mixture, Tien-Hsien Liquid, Induces G2/M Cycle Arrest and Radiosensitivity in MCF-7 Human Breast Cancer Cells through Mechanisms Involving DNMT1 and Rad51 Downregulation
- Author
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Gi-Ming Lai, Shuang-En Chuang, Hui-Ching Kuo, Chih-Jung Yao, Jyh-Ming Chow, Hsin-Lun Lee, Chia-Ming Yang, Chia-Lun Chang, and I-Chun Lai
- Subjects
0301 basic medicine ,biology ,Article Subject ,DNA repair ,Cyclin A ,Cancer ,lcsh:Other systems of medicine ,Cell cycle ,medicine.disease ,lcsh:RZ201-999 ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Complementary and alternative medicine ,MCF-7 ,030220 oncology & carcinogenesis ,Cancer cell ,biology.protein ,Cancer research ,medicine ,Radiosensitivity ,Cyclin B1 ,Research Article - Abstract
The Chinese herbal mixture, Tien-Hsien Liquid (THL), has been proven to suppress the growth and invasiveness of cancer cells and is currently regarded as a complementary medicine for the treatment of cancer. Our previous study using acute promyelocytic leukemia cells uncovered its effect on the downregulation of DNA methyltransferase 1 (DNMT1) which is often overexpressed in cancer cells resulting in the repression of tumor suppressors via hypermethylation. Herein, we explored the effects of THL in MCF-7 breast cancer cells that also demonstrate elevated DNMT1. The results show that THL dose-dependently downregulated DNMT1 accompanied by the induction of tumor suppressors such as p21 and p15. THL arrested cell cycle in G2/M phase and decreased the protein levels of cyclin A, cyclin B1, phospho-pRb, and AKT. DNMT1 inhibition was previously reported to exert a radiosensitizing effect in cancer cells through the repression of DNA repair. We found that THL enhanced radiation-induced clonogenic cell death in MCF-7 cells and decreased the level of DNA double-strand break repair protein, Rad51. Our observations may be the result of DNMT1 downregulation. Due to the fact that DNMT1 inhibition is now a mainstream strategy for anticancer therapy, further clinical trials of THL to confirm its clinical efficacy are warranted.
- Published
- 2016
23. Abstract 3114: In vitro culture system for circulating tumor cell
- Author
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Long Sheng Lu, Lai-Lei Ting, Jeng-Fong Chiou, Chen Yin-Ju, and Hsin-Lun Lee
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,Cancer ,medicine.disease ,Precision medicine ,In vitro ,Breast cancer ,Circulating tumor cell ,Cell culture ,Internal medicine ,Pancreatic cancer ,medicine ,Liquid biopsy ,business - Abstract
Circulating tumor cells (CTCs) detection could be considered a real-time “liquid biopsy” approach and contains several advantages such as being minimally invasive, easy and safe to perform, multiple samples can be taken over time, better prognosis to indicate an elevated risk of metastases, improved therapy monitoring, and providing live disease status information. CTC analysis is a promising new diagnostic field for estimating the risk for metastatic relapse and metastatic progression in patients with cancer. However, the number of CTCs is very low so the establishment of cell culture from CTCs becomes the most challenging over the past year. In this study, we development a cost-effective and reproducible in vitro system for primary CTC cultures or established cell lines from CTCs. 8 CTC cell lines were generated from patients including breast cancer, small cell lung cancer, pancreatic cancer and expanded for more than one year. These cell lines exhibit the tissue-specific markers and also correlated with clinical treatment response from patients. This system provides an opportunity for broad applications of CTCs for personalized oncology and advancing precision medicine. Citation Format: Chen Yin-Ju, Long-Sheng Lu, Hsin-Lun Lee, Lai-Lei Ting, Jeng-Fong Chiou. In vitro culture system for circulating tumor cell [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3114.
- Published
- 2018
24. Identification of subgroup patients with stage IIIB/IV non-small cell lung cancer at higher risk for brain metastases
- Author
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Chi Li Chung, Yu-Ting Chou, Sey En Lin, Shih Hsin Hsiao, Hsin Lun Lee, and H. Eugene Liu
- Subjects
Pulmonary and Respiratory Medicine ,Oncology ,Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,Logistic regression ,Quality of life ,Risk Factors ,Internal medicine ,Carcinoma, Non-Small-Cell Lung ,medicine ,Humans ,Stage (cooking) ,Lung cancer ,Aged ,Neoplasm Staging ,Performance status ,business.industry ,Brain Neoplasms ,Incidence (epidemiology) ,Age Factors ,Middle Aged ,medicine.disease ,Surgery ,Clinical trial ,Adenocarcinoma ,Female ,business - Abstract
Brain metastases (BM), a common occurrence in non-small cell lung cancer (NSCLC), usually lead to a poor prognosis. Recently, the selection of treatment modalities for BM has modestly improved patient survival and quality of life. Treatment choice is largely based on the number of BM, the presence of BM-related symptoms, and performance status. Therefore, early BM detection is crucial. In this study, we aimed to elucidate the factors associated with BM and identify subgroups of patients at higher risk for BM.The medical records of 596 consecutive patients with stage I-IV NSCLC were reviewed between January 2006 and November 2011. A multivariate logistic regression (MLR) model was used to identify factors associated with BM.Among 482 eligible stage IIIB/IV NSCLC patients, 173 (36%) experienced BM during their disease course. On MLR analysis, female gender, age60 years and adenocarcinoma were associated with BM (OR = 1.71, 95% CI = 1.06-2.75, P = 0.028; OR = 2.11, 95% CI = 1.38-3.22, P = 0.001; and OR = 2.39, 95% CI = 1.16-4.92, P = 0.018, respectively). The actuarial incidence of BM varied widely from 14% to 59% in different subgroups; younger patients with adenocarcinoma tended to experience BM more than older patients with squamous cell carcinoma (OR = 6.88, 95% CI = 2.97-15.94, P0.001). Furthermore, the incidence of BM correlated closely with survival after NSCLC diagnosis, and it was 42%, 54% and 64% in patients who survived more than 3, 12 and 24 months, respectively. Notably, the number of BM, the size of the largest BM and the proportion of multiple BM, defined as more than 4 metastatic tumors in brain, were significantly different in NSCLC patients with and without BM-related symptoms or signs (4.0 ± 2.1 vs 2.7 ± 1.9, P0.001; 2.6 ± 1.5 vs 1.3 ± 1.0 CM, P0.001, and 50% vs 21%, P0.001, respectively).We found that subgroups of NSCLC patients characterized by younger age, female gender and adenocarcinoma are at higher risks for BM. These findings might be helpful to detect BM earlier and facilitate the design of clinical trials aiming at their prevention.
- Published
- 2013
25. EGFR Mutations Associated With Superior Intracranial Response and Progression-free Survival After Brain Irradiation in Non-small Cell Lung Cancer With Brain Metastasis
- Author
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E. Liu, Jo-Ting Tsai, I-Chun Lai, Tao-Sang Chung, Lai-Lei Ting, S. Hsiao, Hsin-Lun Lee, Shang Wen Chen, and J. Chiu
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Univariate analysis ,Radiation ,biology ,business.industry ,Hazard ratio ,Bone metastasis ,medicine.disease ,Internal medicine ,medicine ,biology.protein ,Radiology, Nuclear Medicine and imaging ,Progression-free survival ,Epidermal growth factor receptor ,Risk factor ,Lung cancer ,business ,Brain metastasis - Abstract
Purpose/Objective(s): The purpose of this study was to identify the predictive factors of skeletal-related events (SREs) in NSCLC patients with bone metastases. Materials/Methods: Time-to-the first SRE and SRE-free survival and their associations with the patient characteristics were evaluated retrospectively in 416 patients in NSCLC with bone metastatic. Univariate and multivariate statistical methods were used to determine significant risk factors for SRE-free survival. Results: The overall median survival time was 11.5 (9.9-13.2) months from bone metastases. The median observation period for SREs was 8.9 (7.9-9.9) months. Out of 416 patients with bone metastases, 159 (38.2%) developed at least one SRE during or after the initial treatment. On univariate analysis, patients with characteristics such as male, nonadenocarcinoma, ever-smoking, bone metastases with soft-tissue extension and no history of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) therapy had a shorter median time from bone metastasis to first SRE. The results of multivariate analysis revealed that male, bone metastases with soft-tissue extension, no history of EGFR-TKI therapy risk factors for the first SRE, with hazard ratios (HRs) (95% confidence interval [CI]) 1.414 (1.050-1.905), 1.225 (1.030-1.457), 1.731 (1.327-2.259), respectively. Conclusions: The presence of bone metastases with soft-tissue extension was significantly associated with the development of SREs in patients with advanced NSCLC. Male sex and no history of EGFR-TKI therapy were also independent risk factor of development of SREs throughout the course of disease.
- Published
- 2011
26. Distinct Clinical Outcomes of Non-Small Cell Lung Cancer Patients with Epidermal Growth Factor Receptor (EGFR) Mutations Treated with EGFR Tyrosine Kinase Inhibitors: Non-Responders versus Responders
- Author
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Wei Yu Chen, Chii Lan Lin, Zhung Han Wu, Shih Hsin Hsiao, Chi Li Chung, Sey En Lin, H. Eugene Liu, Ling Ling Chiang, and Hsin Lun Lee
- Subjects
Male ,Oncology ,medicine.medical_specialty ,Lung Neoplasms ,Population ,lcsh:Medicine ,Biology ,Epidermal growth factor ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,medicine ,Carcinoma ,Humans ,Epidermal growth factor receptor ,Progression-free survival ,lcsh:Science ,education ,Lung cancer ,Protein Kinase Inhibitors ,Survival analysis ,Aged ,Retrospective Studies ,Aged, 80 and over ,education.field_of_study ,Multidisciplinary ,lcsh:R ,Exons ,Middle Aged ,Prognosis ,medicine.disease ,Survival Analysis ,respiratory tract diseases ,ErbB Receptors ,Treatment Outcome ,Mutation ,Cancer research ,biology.protein ,Female ,lcsh:Q ,Tyrosine kinase ,Research Article - Abstract
INTRODUCTION: Treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) has been associated with favorable progression free survival (PFS) in patients with non-small cell lung cancers (NSCLC) harboring EGFR mutations. However, a subset of this population doesn't respond to EGFR-TKI treatment. Therefore, the present study aimed to elucidate survival outcome in NSCLC EGFR-mutant patients who were treated with EGFR TKIs. METHODS: Among the 580 consecutive NSCLC patients who were treated at our facility between 2008 and 2012, a total of 124 treatment-naïve, advanced NSCLC, EGFR-mutant patients treated with EGFR TKIs were identified and grouped into non-responders and responders for analyses. RESULTS: Of 124 patients, 104 (84%) responded to treatment, and 20 (16%) did not; and the overall median PFS was 9.0 months. Notably, the PFS, overall survival (OS) and survival rates were significantly unfavorable in non-responders (1.8 vs. 10.3 months, hazard ratio (HR) = 29.2, 95% confidence interval (CI), 13.48-63.26, P
- Published
- 2013
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