Publications by authors named "Been-Ren Lin"

52 Publications

Recurrence Outcomes Less Favorable in T1 Rectal Cancer than in T1 Colon Cancer.

Oncologist 2021 May 6. Epub 2021 May 6.

Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.

Background: With the implementation of screening program worldwide, diagnosis of early-stage colorectal cancer steadily increased, including T1 cancer. Current T1 cancer treatment does not differ according to anatomic location. We therefore compared the disease-free survival of T1 cancer arising from rectum versus colon.

Methods: The hospital-based study included subjects with T1 cancer at National Taiwan University Hospital from 2005 to 2014. Clinical, colonoscopy, and histopathology were reviewed for patients with a mean follow-up time of 7.1 (0.7-12.9) years. We conducted Kaplan-Meier analysis to compare the risk of recurrence by cancer location and Cox-regression analysis to identify risk factors for T1 cancer recurrence.

Results: The final cohort included a total of 343 subjects with T1 cancer (mean age, 64.9 ± 11.7 years; 56.1% males), of whom 25 underwent endoscopic resection alone. Of the subjects who underwent surgery, 50 had lymph node metastasis and 268 did not. Kaplan-Meier analysis showed that the risk of recurrence was higher in T1 rectal cancer than T1 colon cancer (p =0.022). Rectal location, and larger neoplasm size were independent risk factors for recurrence, with hazard ratios (95% confidence interval) of 4.84 (1.18-19.92), and 1.32 (1.06-1.65), respectively. The occurrence of advanced histology did not differ between T1 rectal and colon cancers (p = 0.58).

Conclusion: T1 cancers arising from the rectum had less favorable recurrence outcomes than those arising from the colon. Further studies are needed to examine whether adjuvant radiotherapy or chemotherapy can reduce the risk of recurrence in T1 rectal cancer.

Implications For Practice: Current T1 colorectal cancer treatment and surveillance do not differ according to anatomic location. Clinical, colonoscopy, and histopathology were reviewed for 343 T1 cancer patients with a mean follow-up time of 7.1 years. Kaplan-Meier analysis showed that the risk of recurrence was higher in T1 rectal cancer than T1 colon cancer. Moreover, the rectal location was an independent risk factor for recurrence. T1 cancers from the rectum had less favorable recurrence outcomes than those arising from the colon. It is critical to clarify whether adjuvant therapy or more close surveillance can reduce recurrence risk in T1 rectal cancer.
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http://dx.doi.org/10.1002/onco.13815DOI Listing
May 2021

Association between risk factors, molecular features and CpG island methylator phenotype colorectal cancer among different age groups in a Taiwanese cohort.

Br J Cancer 2021 Apr 12. Epub 2021 Apr 12.

Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.

Background: CpG island methylator phenotype (CIMP) represents a carcinogenesis pathway of colorectal cancer (CRC) and the association between CIMP CRC, molecular features and risk factors in East Asian population is less studied.

Methods: We prospectively enrolled newly diagnosed CRC patients at the National Taiwan University Hospital. Clinicopathological data and risk factors for CRC were collected during interview. The tumour samples were subjected to CIMP, RAS/BRAF mutation and microsatellite instability tests. CIMP-high was determined when ≧3 methylated loci of p16, MINT1, MINT2, MINT31 and MLH1 were identified. Multivariate logistic regression was used to evaluate the association between risk factors and CIMP-high CRC.

Results: Compared with CIMP-low/negative CRC, CIMP-high CRC was associated with more stage IV disease, BRAF V600E mutation and high body mass index (BMI ≧ 27.5 kg/m) in younger patients (age < 50 y), and more right-sided tumour, BRAF V600E mutation, MSI-high and colorectal polyp in elder patients (age ≧ 50 y). Multivariate analyses showed that BMI ≧27.5 kg/m was significantly associated with CIMP-high CRC in younger patients.

Conclusions: We identified distinct clinicopathological features for CIMP-high CRC among different age groups in Taiwan. Our data suggest the association between BMI ≧27.5 kg/m and CIMP-high CRC in patients younger than 50 years.
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http://dx.doi.org/10.1038/s41416-021-01300-5DOI Listing
April 2021

Downstaged ypT0-2N0 rectal cancer after neoadjuvant chemoradiation therapy may not need adjuvant chemotherapy: a retrospective cohort study.

Int J Colorectal Dis 2021 Mar 30;36(3):509-516. Epub 2020 Oct 30.

Division of Colorectal Surgery, Department of Surgery, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan, Republic of China.

Purpose: Current guidelines suggest that adjuvant chemotherapy (AC) be administered to all locally advanced (clinically T3-4 or N-positivity) rectal cancer patients undergoing neoadjuvant chemoradiotherapy (nCRT) and radical surgical resection regardless of the final pathological staging (yp staging). This study aimed to evaluate the necessity of AC for ypT0-2N0 rectal cancer.

Methods: Patients with ypT0-2N0 rectal cancer, who received nCRT and radical surgical resection, were recruited retrospectively at a university hospital. The main outcome was to evaluate the 5-year overall survival (OS) and disease-free survival (DFS) between ypT0-2N0 rectal cancer patients with AC and those without AC. We also identified potential independent prognostic factors associated with poor outcomes.

Results: One hundred and ten ypT0-2N0 rectal cancer patients (ypT0: n = 6; ypT1: n = 44; ypT2: n = 60) were followed up for a median of 60 months. No significant difference was observed in DFS and 5-year OS between patients with AC and those without AC. The risk of recurrence was associated with the postoperative pathological staging (0% with ypT0, 2.4% with ypT1, and 10% with ypT2). In the multivariate analysis, retrieval of < 12 lymph nodes was an independent favorable prognostic factor, which correlated with a higher OS (HR: 2.263; 95% CI: 1.093-4.687, P = 0.028). Intra-tumor lymphovascular and perineural invasion were poor prognostic markers for shorter DFS (HR: 5.940; 95% CI: 1.150-30.696, P = 0.033).

Conclusion: Postoperative AC is not required for patients with ypT0-2N0 rectal cancer downstaged by nCRT, especially in those without poor prognostic factors.
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http://dx.doi.org/10.1007/s00384-020-03787-5DOI Listing
March 2021

Trifluridine/tipiracil in combination with local therapy may be a favorable option for refractory metastatic colorectal cancer patients: A case report.

Medicine (Baltimore) 2020 Oct;99(43):e22780

Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.

Rationale: Currently, the 5-year survival rate remains poor for patients with metastatic colorectal cancer (mCRC), and the purpose of therapy is to prolong survival while maintaining the quality of life. Trifluridine/tipiracil, an oral drug combining trifluorothymidine and a thymidine phosphorylase inhibitor, is indicated as salvage therapy for mCRC patients who have progressed after all available regimens. Combination of local treatments with systemic therapy such as trifluridine/tipiracil represents an apt management strategy for mCRC patients.

Patient Concerns: A 72-year-old man diagnosed with stage IV rectal adenocarcinoma (KRAS mutation) with peritoneal carcinomatosis and liver metastases developed resistance to 2 lines of treatment (bevacizumab/irinotecan/S-1 and bevacizumab/oxaliplatin/HDFL [high-dose 24-hour infusion of 5-fluorouracil and leucovorin regimen]) within 5 months.

Diagnosis: Refractory stage IV rectal adenocarcinoma.

Interventions: Systemic treatment of trifluridine/tipiracil has been given for approximately 15 months in addition to radiotherapy, Yttrium-90 radioembolization, and trans-arterial chemoembolization for peritoneal and liver metastases.

Outcomes: After 15 months, the patient was still taking trifluridine/tipiracil for disease control with a good quality of life.

Lessons: Trifluridine/tipiracil plus other appropriate local therapy may significantly prolong patients survival with a satisfactory quality of life for patients with refractory mCRC. The favorable safety profile of trifluridine/tipiracil renders it a suitable option to be combined with other local therapies for metastatic lesions.
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http://dx.doi.org/10.1097/MD.0000000000022780DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7581032PMC
October 2020

Glucose Metabolites Exert Opposing Roles in Tumor Chemoresistance.

Front Oncol 2019 21;9:1282. Epub 2019 Nov 21.

Graduate Institute of Physiology, National Taiwan University College of Medicine, Taipei, Taiwan.

Reprogrammed glucose metabolism and increased glycolysis have been implicated in tumor chemoresistance. The aim was to investigate the distinct roles of the glucose metabolites pyruvate and ATP in chemoresistance mechanisms, including cell death and proliferation. Our data showed higher glucose transporters in colorectal cancer (CRC) from non-responsive patients than those responsive to chemotherapy. Human CRC cell lines exposed to 5-fluorouracil (5-FU) displayed elevated cell viability and larger tumors in xenograft mouse models if cultured in high-glucose medium. Glucose conferred resistance to 5-FU-induced necroptosis via pyruvate scavenging of mitochondrial free radicals, whereas ATP replenishment had no effect on cell death. Glucose attenuated the 5-FU-induced G0/G1 shift but not the S phase arrest. Opposing effects were observed by glucose metabolites; ATP increased while pyruvate decreased the G0/G1 shift. Lastly, 5-FU-induced tumor spheroid destruction was prevented by glucose and pyruvate, but not by ATP. Our finding argues against ATP as the main effector for glucose-mediated chemoresistance and supports a key role of glycolytic pyruvate as an antioxidant for dual modes of action: necroptosis reduction and a cell cycle shift to a quiescent state.
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http://dx.doi.org/10.3389/fonc.2019.01282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6881467PMC
November 2019

Using serum placenta growth factor could improve the sensitivity of colorectal cancer screening in fecal occult blood negative population: A multicenter with independent cohort validation study.

Cancer Med 2019 07 7;8(7):3583-3591. Epub 2019 May 7.

Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.

Background: Colorectal cancer (CRC) is one of the most common cancers worldwide. Screening for CRC using the fecal occult blood test (FOBT) is feasible and useful for decreasing disease-related mortality; however, its sensitivity and compliance are unsatisfactory.

Methods: This study examined the efficacy of using serum placenta growth factor (PlGF) for a novel CRC screening strategy. To investigate a potential novel screening tool for CRC, we compared the sensitivity, specificity, positive predictive value, and negative predictive value of the FOBT, serum PlGF, and their combination through an examination of two independent cohorts and validation using the second cohort. All the patients and control group received the colonoscopy and FOBT, the colonoscopy was used as the gold standard for the result.

Results: Serum PlGF levels were significantly increased in CRC patients (16.8 ± 11.4 pg/mL) compared with controls (12.0 ± 11.2 pg/mL). The predictive model that used the serum PlGF level alone was as effective as the FOBT (AUC: 0.60 vs 0.68, P = 0.891), and it had significantly higher sensitivity than the FOBT (0.81 vs 0.39). In addition, we found serum PlGF level has a good value for predicting CRC patients in those FOBT negative populations. Finally, combining serum PlGF level and the FOBT improved the predictive power and demonstrated satisfactory sensitivity (0.71) and specificity (0.71). This result was confirmed and validated in the second independent cohort. Furthermore, no matter the stages (early/advanced) and the location (distal/proximal) of CRC, the efficacy of serum PlGF and the combined model remained quite stable.

Conclusion: Serum PlGF level is a potential alternative screening tool for CRC, especially for those who are reluctant to stool-based screening methods and who were tested as negative FOBT. In addition, combining serum PlGF level and the FOBT could increase the power of CRC screening.
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http://dx.doi.org/10.1002/cam4.2216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6601572PMC
July 2019

CpG Island Methylator Phenotype May Predict Poor Overall Survival of Patients with Stage IV Colorectal Cancer.

Oncology 2019 12;96(3):156-163. Epub 2018 Dec 12.

Department of Oncology, National Taiwan University Hospital, Taipei City, Taiwan,

Objective: We aimed to study the prognostic role of CpG island methylator phenotype (CIMP) in patients with different stages of colorectal cancer (CRC).

Material And Methods: We analyzed CIMP in stage I-IV CRC specimens from patients who were diagnosed between 2005 and 2013. CIMP status was determined using a 5-gene MethyLight-based assay. The clinicopathologic characteristics were reviewed and the overall survival (OS) was compared between patients with CIMP-high CRC and those with CIMP-low/negative CRC.

Results: Among 450 CRC specimens with successfully determined CIMP statuses, 74 (16.4%) were CIMP-high CRC. Although there was no difference in OS between patients with CIMP-high and CIMP-low/negative CRC across all stages (p = 0.4526), intriguingly, patients with stage IV CIMP-high CRC had significantly worse OS than those with stage IV CIMP-low/negative CRC (p = 0.0047). In a multivariate analysis, CIMP status remained an independent prognostic factor for overall mortality (HR = 5.60, 95% CI: 2.12-14.79, p = 0.0005) in metastatic CRC after adjusting for clinicopathologic variables and anti-cancer therapies.

Conclusion: Our results revealed that the presence of CIMP independently predicts poor OS in patients with stage IV CRC.
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http://dx.doi.org/10.1159/000493387DOI Listing
March 2019

Three Nurse-administered Protocols Reduce Nutritional Decline and Frailty in Older Gastrointestinal Surgery Patients: A Cluster Randomized Trial.

J Am Med Dir Assoc 2019 05 10;20(5):524-529.e3. Epub 2018 Nov 10.

Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts; Institute for Aging Research, Hebrew Senior Life, Boston, Massachusetts.

Objective: To evaluate the effects of the modified Hospital Elder Life Program (mHELP) comprising 3 nurse-administered protocols in older patients undergoing gastrointestinal (GI) surgery.

Design: Cluster randomized trial.

Setting: Two 36-bed GI wards at a university-affiliated medical center in Taiwan.

Participants: Older patients (≥65 years, N = 377) were recruited if they were scheduled for elective GI surgery with an expected length of hospital stay >6 days. After transferring to the GI ward after surgery, participants were randomly assigned to the mHELP or control group (1:1) by room rather than individually because most patient units are double- or triple-occupancy rooms.

Intervention: The mHELP protocols (early mobilization, oral and nutritional assistance, and orienting communication) were administered daily with usual care by a trained nurse until hospital discharge. The control group received usual care only.

Measures: Outcomes were in-hospital nutritional decline, measured by body weight and Mini-Nutritional Assessment (MNA) scores, and Fried's frailty phenotype. Return of GI motility was examined as a potential mechanism contributing to observed outcomes.

Results: Participants (mean age = 74.5 years; 56.8% male) primarily underwent colorectal (56.5%), gastric (21.2%), and pancreatobiliary (13.8%) surgery. Participants who received the mHELP [for a median of 7 days (interquartile range = 6-10 days)] had significantly lower in-hospital weight loss and decline in MNA scores (weight -2.1 vs -4.0 lb, P = .002; score -3.2 vs -4.0, P = .03) than the control group. The mHELP group also had significantly lower rates of incident frailty during hospitalization (12.0% vs 21.7%, P = .022), and persistent frailty (50.0% vs 92.9%, P = .03). Participants in the mHELP group had trends toward an accelerated return of GI motility.

Conclusion And Implications: The mHELP effectively reduced nutritional decline, prevented new frailty, and promoted recovery of frailty present before admission. These nurse-administered protocols might be useful in other settings, including conditions managed at home or in nursing facilities.
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http://dx.doi.org/10.1016/j.jamda.2018.09.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6607892PMC
May 2019

Adjunctive use of chromoendoscopy may improve the diagnostic performance of narrow-band imaging for small sessile serrated adenoma/polyp.

J Gastroenterol Hepatol 2018 Feb;33(2):466-474

Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.

Background And Aim: Endoscopic diagnosis of sessile serrated adenoma/polyp (SSA/P) is challenging because of their subtle appearance. Narrow-band imaging (NBI) is useful for diagnosis, but its utility with concurrent chromoendoscopy (CE), especially to detect small SSA/P, is unproven.

Methods: This prospective study enrolled 367 consecutive patients who underwent screening colonoscopy with the finding of serrated polyps. Patients were divided into derivation and validation cohorts: Diagnostic criteria using different endoscopic modalities were generated by regression analysis in the derivation cohort and were validated in the validation cohort for sensitivity, specificity, and accuracy.

Results: There were 180 patients with 119 SSA/P and 147 hyperplastic polyps (HP) in the derivation cohort and 187 patients with 177 SSA/P and 125 HP in the validation cohort. With white-light endoscopy plus NBI, mucus cap, surface grooves, and expanded crypt were most associated with SSA/P. With white-light endoscopy plus CE, II-O pit pattern, mucus cap, and superficial telangiectasia were most associated with SSA/P. With the combined use of these three modalities, II-O pit pattern, mucus cap, and surface grooves were most associated with SSA/P. For large serrated polyp, NBI in combination with CE had a better accuracy than NBI alone (91% vs 86%, P = 0.025) to distinguish SSA/P from HP. CE alone had a better accuracy than NBI alone for distinguishing small SSA/P from small HP (85% vs 72%, P < 0.0001).

Conclusion: Compared with NBI alone, adjunctive use of CE can improve the diagnostic accuracy for distinguishing SSA/P from HP, especially for small SSA/P.
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http://dx.doi.org/10.1111/jgh.13863DOI Listing
February 2018

PET/MRI for evaluating subclinical inflammation of ulcerative colitis.

J Magn Reson Imaging 2018 03 22;47(3):737-745. Epub 2017 Jun 22.

Department of Medical Imaging, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.

Purpose: To explore the utility of integrated positron emission tomography (PET) / magnetic resonance imaging (MRI) for evaluating subclinical inflammation in patients with ulcerative colitis (UC).

Materials And Methods: This prospective study was approved by the Institutional Review Board and informed consent was obtained. Between November 2015 and April 2016, 19 consecutive patients with UC in clinical remission were enrolled. These patients underwent 18F-fluorodeoxyglucose PET/MRI (3T) and colonoscopy. Serum high-sensitivity C-reactive protein (hs-CRP) and fecal calprotectin (FC) levels were also obtained. The findings of colonoscopy were graded using the Mayo endoscopic subscore. Quantitative (minimum apparent diffusion coefficient [ADC ] and maximum standardized uptake value [SUV ]), semiquantitative, and qualitative parameters of PET/MRI were evaluated and correlated with colonoscopic findings.

Results: In per-segment analysis, ADC was significantly lower and SUV and ratio of SUV to ADC were significantly higher in the colonic segments with active inflammation (Mayo endoscopic subscore ≥2) (P < 0.05). Qualitative MRI score, PET activity grade, and PET/MRI score were also significantly higher in the colonic segments with active inflammation (P < 0.05). Among these parameters, the ratio of SUV to ADC exhibited the highest area under the receiver operating characteristic curve (AUC) (0.763). In per-patient analysis, the AUC of PET activity grade was 0.778, higher than those of hs-CRP (0.589) and FC (0.722). Using a combined index of FC and PET, an even higher AUC (0.867) was achieved.

Conclusion: PET/MRI is a potentially useful tool in identifying subclinical inflammation in patients with UC.

Level Of Evidence: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:737-745.
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http://dx.doi.org/10.1002/jmri.25795DOI Listing
March 2018

Effect of a Modified Hospital Elder Life Program on Delirium and Length of Hospital Stay in Patients Undergoing Abdominal Surgery: A Cluster Randomized Clinical Trial.

JAMA Surg 2017 Sep;152(9):827-834

Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.

Importance: Older patients undergoing abdominal surgery commonly experience preventable delirium, which extends their hospital length of stay (LOS).

Objective: To examine whether a modified Hospital Elder Life Program (mHELP) reduces incident delirium and LOS in older patients undergoing abdominal surgery.

Design, Setting, And Participants: This cluster randomized clinical trial of 577 eligible patients enrolled 377 older patients (≥65 years of age) undergoing gastrectomy, pancreaticoduodenectomy, and colectomy at a 2000-bed urban medical center in Taipei, Taiwan, from August 1, 2009, through October 31, 2012. Consecutive older patients scheduled for elective abdominal surgery with expected LOS longer than 6 days were enrolled, with a recruitment rate of 65.3%. Participants were cluster randomized by room to receive the mHELP or usual care.

Interventions: The intervention (implemented by an mHELP nurse) consisted of 3 protocols administered daily: orienting communication, oral and nutritional assistance, and early mobilization. Intervention group participants received all 3 mHELP protocols postoperatively, in addition to usual care, as soon as they arrived in the inpatient ward and until hospital discharge. Adherence to protocols was tracked daily.

Main Outcomes And Measures: Presence of delirium was assessed daily by 2 trained nurses who were masked to intervention status by using the Confusion Assessment Method. Data on LOS were abstracted from the medical record.

Results: Of 577 eligible patients, 377 (65.3%) were enrolled and randomly assigned to the mHELP (n = 197; mean [SD] age, 74.3 [5.8] years; 111 [56.4%] male) or control (n = 180; mean [SD] age, 74.8 [6.0] years; 103 [57.2%] male) group. Postoperative delirium occurred in 13 of 196 (6.6%) mHELP participants vs 27 of 179 (15.1%) control individuals, representing a relative risk of 0.44 in the mHELP group (95% CI, 0.23-0.83; P = .008). Intervention group participants received the mHELP for a median of 7 days (interquartile range, 6-10 days) and had a shorter median LOS (12.0 days) than control participants (14.0 days) (P = .04).

Conclusions And Relevance: For older patients undergoing abdominal surgery who received the mHELP, the odds of delirium were reduced by 56% and LOS was reduced by 2 days. Our findings support using the mHELP to advance postoperative care for older patients undergoing major abdominal surgery.

Trial Registration: clinicaltrials.gov Identifier: NCT01045330.
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http://dx.doi.org/10.1001/jamasurg.2017.1083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5710459PMC
September 2017

Polypoid lesions at the anal canal: what do they hint?

Intest Res 2017 Jan 31;15(1):142-143. Epub 2017 Jan 31.

Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.

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http://dx.doi.org/10.5217/ir.2017.15.1.142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5323306PMC
January 2017

Ataxia-telangiectasia mutated interactor regulates head and neck cancer metastasis via KRas expression.

Oral Oncol 2017 03 21;66:100-107. Epub 2016 Dec 21.

Angiogenesis Research Center, National Taiwan University, Taiwan; Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan. Electronic address:

Objectives: Relapse is the most serious problem affecting the morbidity and mortality rates of patients with head and neck squamous cell carcinoma (HNSCC). Although HNSCC has been studied for several decades, the exact mechanism of cancer recurrence remains unclear.

Materials And Methods: ataxia-telangiectasia mutated interactor (ATMIN) messenger RNA(mRNA) expression was detected in HNSCC samples by quantitative RT-PCR, and was analyzed with patients' clinical outcomes by Kaplan-Meier analyses. The ectopic ATMIN expression or ATMIN silencing on invasion ability was evaluated in HNSCC cell lines. Lymph node metastasis ability was investigated by buccal orthotopic implantation in vivo. All statistical tests were two-sided.

Results: ATMIN mRNA expression was positively correlated with patients' clinical outcomes. ATMIN blockage reduced invasion, migration, and metastasis abilities both in vitro and in vivo. Evidence from a buccal orthotopic implantation mice model showed that silenced ATMIN expression prolongs mice survival and reduced lymph node metastasis. In high-throughput microarray and bioinformative analyses, KRas was identified as a crucial downstream effector in ATMIN-mediated HNSCC metastasis and was positively associated with patients' clinical stages and ATMIN mRNA expression.

Conclusions: The role of ATMIN and its regulatory mechanisms in HNSCC progression are reported for the first time. The study results improve our understanding of the ATMIN-KRas axis leading to HNSCC migration or invasion and metastasis and facilitates the identification of possible therapy targets of downstream genes for designing effective therapeutic strategies in personalized medicine.
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http://dx.doi.org/10.1016/j.oraloncology.2016.11.006DOI Listing
March 2017

HMGCS2 enhances invasion and metastasis via direct interaction with PPARα to activate Src signaling in colorectal cancer and oral cancer.

Oncotarget 2017 Apr;8(14):22460-22476

Department of Surgery, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.

Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (HMGCS2) is the rate-limiting enzyme of ketogenesis. Growing evidence indicates that HMGCS2 may be involved in cancer progression, but its exact role is largely unknown. In this study, we demonstrate that HMGCS2 mRNA expression is associated with poor clinical prognosis and outcomes in patients with colorectal cancer (CRC) and oral squamous cell carcinoma (OSCC). In vitro, ectopic expression of HMGCS2 enhanced cancer cell motility in a ketogenesis-independent manner. Moreover, HMGCS2 promoted Src activity by directly binding to peroxisome proliferator-activated receptor alpha (PPARα), a transcriptional activator of Src. Taken together, these results suggest that HMGCS2 may serve as a useful prognostic marker and vital target for future therapeutic strategies against advanced cancer.
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http://dx.doi.org/10.18632/oncotarget.13006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5410236PMC
April 2017

Fecal Immunochemical Test Detects Sessile Serrated Adenomas and Polyps With a Low Level of Sensitivity.

Clin Gastroenterol Hepatol 2017 Jun 4;15(6):872-879.e1. Epub 2016 Aug 4.

Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Health Management Center, National Taiwan University Hospital, Taipei, Taiwan. Electronic address:

Background & Aims: The serrated pathway is a distinct pathway of colorectal carcinogenesis that has been implicated in development of a substantial proportion of interval colorectal cancers. The fecal immunochemical test (FIT) detects early neoplasms with a higher level of sensitivity than the guaiac test. We investigated the sensitivity of the FIT in detection of sessile serrated adenomas/polyps (SSA/Ps).

Methods: We performed a prospective study of 6198 asymptomatic subjects (mean age, 59.0 ± 7.0 years) who received concurrent screening colonoscopies and FITs at the Health Management Center of National Taiwan University Hospital from August 2010 through November 2014. The sensitivity of FIT for conventional adenoma, advanced adenoma, and SSA/P at different cutoffs was calculated, and results were compared by using multivariate analysis adjusted for potential confounders.

Results: Prevalence values of SSA/P, adenoma, and advanced adenoma were 1.4%, 20.2%, and 5.5%, respectively. At cutoffs of 10, 15, and 20 μg hemoglobin/g feces, the FIT detected all SSA/Ps with 12.3%, 6.2%, and 6.2% sensitivity, large SSA/Ps with 18.4%, 10.5%, and 10.5% sensitivity, and advanced adenomas with 32.4%, 24.5%, and 20.9% sensitivity, respectively. Multivariate analysis revealed that positive results from the FIT did not differ significantly between individuals with SSA/P and those with non-advanced adenoma or those with negative findings from colonoscopy. Patients with large SSA/Ps were less likely to have positive results from the FIT than patients with advanced adenoma, with odds ratios of 0.44 (95% confidence interval [CI], 0.18-1.05), 0.30 (95% CI, 0.10-0.90), and 0.37 (95% CI, 0.12-1.12) at cutoffs of 10, 15, and 20 μg hemoglobin/g feces, respectively, after adjusting for lesion size, even with synchronous conventional adenoma.

Conclusions: In a prospective study of 6198 subjects receiving the FIT and colonoscopy, we found that the FIT detected SSA/Ps with significantly lower levels of sensitivity than conventional adenoma. Further studies are needed to determine the effects of these findings on the effectiveness of FIT-based colorectal cancer screening program.
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http://dx.doi.org/10.1016/j.cgh.2016.07.029DOI Listing
June 2017

A retrospective analysis of 20-year data of the surgical management of ulcerative colitis patients in Taiwan: a study of Taiwan Society of Inflammatory Bowel Disease.

Intest Res 2016 Jul 27;14(3):248-57. Epub 2016 Jun 27.

Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital and Department of Surgery, National Yang-Ming University, Taipei, Taiwan.

Background/aims: With the recent progress in medical treatment, surgery still plays a necessary and important role in treating ulcerative colitis (UC) patients. In this study, we analyzed the surgical results and outcomes of UC in Taiwan in the recent 20 years, via a multi-center study through the collaboration of Taiwan Society of IBD.

Methods: A retrospective analysis of surgery data of UC patients from January 1, 1995, through December 31, 2014, in 6 Taiwan major medical centers was conducted. The patients' demographic data, indications for surgery, and outcome details were recorded and analyzed.

Results: The data of 87 UC patients who received surgical treatment were recorded. The median post-operative follow-up duration was 51.1 months and ranged from 0.4 to 300 months. The mean age at UC diagnosis was 45.3±16.0 years and that at operation was 48.5±15.2 years. The 3 leading indications for surgical intervention were uncontrolled bleeding (16.1%), perforation (13.8%), and intractability (12.6%). In total, 27.6% of surgeries were performed in an emergency setting. Total or subtotal colectomy with rectal preservation (41.4%) was the most common operation. There were 6 mortalities, all due to sepsis. Emergency operation and low pre-operative albumin level were significantly associated with poor survival (P=0.013 and 0.034, respectively).

Conclusions: In the past 20 years, there was no significant change in the indications for surgery in UC patients. Emergency surgeries and low pre-operative albumin level were associated with poor survival. Therefore, an optimal timing of elective surgery for people with poorly controlled UC is paramount.
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http://dx.doi.org/10.5217/ir.2016.14.3.248DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4945529PMC
July 2016

Factors Influencing Amount of Weekly Exercise Time in Colorectal Cancer Survivors.

Cancer Nurs 2017 May/Jun;40(3):201-208

Author Affiliations: School of Nursing (Ms Chou, Drs Lai and Shun), College of Medicine, National Taiwan University; and Department of Surgery (Drs Lin and Liang), National Taiwan University Hospital, Taipei, Taiwan.

Background: Performing regular exercise of at least 150 minutes weekly has benefits for colorectal cancer survivors. However, barriers inhibit these survivors from performing regular exercise.

Objectives: The aim of this study was to explore exercise behaviors and significant factors influencing weekly exercise time of more than 150 minutes in colorectal cancer survivors.

Methods: A cross-sectional study design was used to recruit participants in Taiwan. Guided by the ecological model of health behavior, exercise barriers were assessed including intrapersonal, interpersonal, and environment-related barriers. A multiple logistic regression was used to explore the factors associated with the amount of weekly exercise.

Results: Among 321 survivors, 57.0% of them had weekly exercise times of more than 150 minutes. The results identified multiple levels of significant factors related to weekly exercise times including intrapersonal factors (occupational status, functional status, pain, interest in exercise, and beliefs about the importance of exercise) and exercise barriers related to environmental factors (lack of time and bad weather). No interpersonal factors were found to be significant.

Conclusions: Colorectal cancer survivors experienced low levels of physical and psychological distress. Multiple levels of significant factors related to exercise time including intrapersonal factors as well as exercise barriers related to environmental factors should be considered.

Implications For Practice: Healthcare providers should discuss with their patients how to perform exercise programs; the discussion should address multiple levels of the ecological model such as any pain problems, functional status, employment status, and time limitations, as well as community environment.
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http://dx.doi.org/10.1097/NCC.0000000000000383DOI Listing
August 2017

Local Control by Radiofrequency Thermal Ablation Increased Overall Survival in Patients With Refractory Liver Metastases of Colorectal Cancer.

Medicine (Baltimore) 2016 Apr;95(14):e3338

From the Department of Surgery, National Taiwan University Hospital Hsinchu Branch, Hsinchu (P-CY); Department of Surgery (B-RL, H-SL, K-WH, J-TL); Department of Medical Imaging (Y-CC); and Department of Oncology, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan, ROC (Y-LL).

Radiofrequency thermal ablation (RFA) is widely used for local solitary liver tumor control. However, the benefit of RFA for colorectal cancer with liver metastases, which is refractory to chemotherapy, remains unknown.We retrospectively enrolled 70 consecutive colorectal adenocarcinoma patients, who had synchronous liver metastases, who were refractory to chemotherapy, and whose life expectancy was >6 months, into this study to investigate the outcomes of RFA and associated prognostic factors. RFA was introduced to all of these patients during the enrollment. The time interval from RFA to recurrence of liver metastases and overall survival was recorded. Age, sex, carcinoembryonic antigen level, primary tumor location, postoperative adjuvant chemotherapy regimens, and the size and number of metastatic liver lesions were recorded. Cox regression analysis was used to determine the prognostic significance.Thirty-nine patients accepted RFA during chemotherapy, whereas 31 chose to receive chemotherapy alone. Patients with ≤5 and >5 liver metastases had median survival durations of 28 and 17 months, respectively (P = 0.018). The dominant liver tumor size (<5 vs ≥5 cm) was significantly associated with median survival (30 vs 17 months, respectively; P = 0.038), as was the carcinoembryonic antigen level (35 vs 16 months for ≤200 vs >200 ng/mL respectively; P = 0.029). Besides, radiofrequency thermal ablation plus chemotherapy was associated with a better median overall survival than chemotherapy alone (29 vs 12 months, respectively; P = 0.002). In multivariate analysis, only radiofrequency thermal ablation treatment and number of liver tumors were significant prognostic factors for survival. Our result further revealed that patients treated with radiofrequency thermal ablation had longer progression-free intervals than those treated with chemotherapy alone (18 vs 9 months, respectively; P = 0.001). Hence, radiofrequency thermal ablation is a safe and effective adjunct treatment to chemotherapy.
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http://dx.doi.org/10.1097/MD.0000000000003338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4998829PMC
April 2016

BRAF mutation may have different prognostic implications in early- and late-stage colorectal cancer.

Med Oncol 2016 May 31;33(5):39. Epub 2016 Mar 31.

Department of Oncology, National Taiwan University Hospital, No 7, Chung-Shan South Rd, Taipei, 10002, Taiwan.

The prognostic implication of BRAF mutant colorectal cancer remains paradoxical. Records of BRAF mutant and wild-type colorectal cancer patients at all stages were reviewed. Clinicopathologic features, including microsatellite instability, CpG islands methylator phenotype, and overall survival, of these patients were analyzed. Between 2005 and 2013, 428 colorectal cancer patients were enrolled in this study. The overall survival between BRAF mutant and wild-type patients with early-stage (stages I and II) colorectal cancer differed nonsignificantly (P = 0.99). By contrast, in late-stage (stages III and IV) patients, the median overall survival of BRAF mutant patients (N = 25) was significantly poorer than that of BRAF wild-type (N = 207) patients (BRAF mutant: 21.3 months (95% confidence interval [CI] 7.1-35.5); BRAF wild-type: 53.5 months (95% CI 37.5-69.5), P < 0.0001). In early-stage patients, we found that BRAF mutation was significantly associated with CpG island methylator phenotype-positive (P < 0.001), and microsatellite instability-high status (P = 0.0013). Conversely, in late-stage patients, BRAF mutation was significantly associated with CpG island methylator phenotype-positive (P = 0.0015) and the right-side colon (P = 0.014). BRAF mutation may have different prognostic implications in early- and late-stage colorectal cancer.
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http://dx.doi.org/10.1007/s12032-016-0756-6DOI Listing
May 2016

Postoperative Showering for Clean and Clean-contaminated Wounds: A Prospective, Randomized Controlled Trial.

Ann Surg 2016 May;263(5):931-6

*Department of Nursing, National Taiwan University College of Medicine, Taipei, Taiwan †Department of Surgery, National Taiwan University College of Medicine, Taipei, Taiwan ‡Institute of Statistical Science, Academia Sinica, National Taiwan University College of Medicine, Taipei, Taiwan §Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan ¶Department of Medical Research, National Taiwan University College of Medicine, Taipei, Taiwan ||Department of Traumatology, National Taiwan University College of Medicine, Taipei, Taiwan **School of Nursing, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.

Objective: To evaluate wound infection rates, pain scores, satisfaction with wound care, and wound care costs starting 48 hours after surgery.

Background: Showering after surgery is a controversial issue for wound care providers and patients. We investigated the benefits and detriments of showering for postoperative wound care.

Methods: Patients undergoing thyroid, lung, inguinal hernia, and face and extremity surgeries with clean or clean-contaminated wounds were included. The patients were randomized to allow showering (shower group) or to keep the wound dry (nonshower group) for postoperative wound care starting 48 hours after surgery. The primary endpoint was the rate of surgical wound infection. The secondary endpoints included the wound pain score, satisfaction with wound care, and cost of wound care.

Results: Between May 2013 and March 2014, there were 222 patients randomized to the shower group and 222 to the nonshower group. Two patients in each group were lost to follow-up. There were 4 superficial surgical site infections in the shower group and 6 in the nonshower group (4/220, 1.8% vs 6/220, 2.7%, P = 0.751). Postoperative pain scores were comparable between the 2 groups. Patients in the shower group were more satisfied with their method of wound care, and their wound care costs were lower when compared with the nonshower group.

Conclusions: Clean and clean-contaminated wounds can be safely showered 48 hours after surgery. Postoperative showering does not increase the risk of surgical site complications. It may increase patients' satisfaction and lower the cost of wound care.
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http://dx.doi.org/10.1097/SLA.0000000000001359DOI Listing
May 2016

Suppression of fructose-bisphosphate aldolase C expression as a predictor of advanced oral squamous cell carcinoma.

Head Neck 2016 04 13;38 Suppl 1:E1075-85. Epub 2015 Nov 13.

Angiogenesis Research Center, National Taiwan University, Taipei, Taiwan.

Background: Glycolysis machinery regulates cancer cell behavior. However, the roles of these glycolysis enzymes in oral squamous cell carcinoma (OSCC) progression remain unknown.

Methods: Fructose-bisphosphate aldolase C (ALDOC) expression in OSCC patients and cell lines was detected using quantitative real-time polymerase chain reaction (PCR). The functions of ALDOC in migration and invasion were determined using gain and loss of function approaches. An orthotopic OSCC animal model was performed to investigate the effects of ALDOC on metastasis and tumorigenesis in vivo.

Results: ALDOC expression is negatively significantly correlated with clinical outcome and cell migration in vitro and in vivo. ALDOC blocks adenosine triphosphate generation and lactate production, and mutation constructs of Arg42 and Lys146 functionally restore ALDOC-inhibited cell migration and invasion.

Conclusion: ALDOC functions as an OSCC prognosis marker clinically, and suppresses migration and invasion by its catalytic domain of Arg42 and Lys146. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1075-E1085, 2016.
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http://dx.doi.org/10.1002/hed.24161DOI Listing
April 2016

Lymph node trafficking of regulatory T cells is prerequisite for immune suppression.

J Leukoc Biol 2016 Apr 5;99(4):561-8. Epub 2015 Nov 5.

Departments of *Medical Research, Pediatrics, Graduate Institute of Clinical Medicine, School of Medicine, and Department of General Surgery, National Taiwan University Hospital, Taipei, Taiwan

Regulatory T cells have a crucial role in health and disease because of their immune regulation function. However, the anatomic sites where regulatory T cells exert optimal immune regulation are open to debate. In our current study with the use of a shear-stress flow assay, we found that regulatory T cells exhibited significantly decreased adhesion to either activated endothelial monolayer or intercellular adhesion molecule 1 or E-selectin-coated surfaces compared with activated effector T cells. The less transmigration capacity of the regulatory T cells prompted our speculation of preferential lymph node localization for the regulatory T cells that endowed these cells with immune regulation function in the most efficient manner. To test this hypothesis, the role of lymph node localization in regulatory T cell-mediated immune suppression was evaluated with a footpad inflammation model. We found that adoptively transferred regulatory T cells inhibited the development of footpad inflammation. In addition, although blockage of CCR7 or CD62L had no effect on the immune suppressive function of the regulatory T cells per se, pretreatment of the regulatory T cells with either CCR7 or CD62L blocking antibodies prevented their recruitment into draining lymph nodes and concomitantly abrogated the immune suppressive effects of adoptively transferred regulatory T cells during footpad inflammation. Our data demonstrate the crucial role of lymph node localization in regulatory T cell-mediated immune suppression and suggest a probable hierarchy in the anatomic sites for optimal immune regulation. Elucidating the relationships between the transmigration characteristics of the regulatory T cells and their immune regulation function will provide insightful information for regulatory T cell-based cell therapy.
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http://dx.doi.org/10.1189/jlb.1A0715-296RDOI Listing
April 2016

Overall Survival of Stage III Colon Cancer with Only One Lymph Node Metastasis Is Independently Predicted by Preoperative Carcinoembryonic Antigen Level and Lymph Node Sampling Status.

PLoS One 2015 18;10(9):e0137053. Epub 2015 Sep 18.

Division of Colorectal Surgery, Department of Surgery, National Taiwan University Hospital and College of Medicine, No. 7, Chung-Shan South Road, Taipei, Taiwan, ROC.

Background: This study identified predictors of favorable overall survival (OS) for stage III colon cancer patients who had only one lymph node (LN) metastasis (N1a).

Methods: Variables, including preoperative carcinoembryonic antigen (CEA) level, LN sampling status, and the choices of postoperative adjuvant chemotherapy, were recorded. Prognostic significance was determined using the log-rank test and multivariate Cox regression analysis.

Results: The median 42-month follow-up period included 363 eligible patients. Among them, 230 (63.3%) received only 5-flurouracil (5-FU) adjuvant chemotherapy; 76 (20.9%) underwent oxaliplatin-based regimens; and 57 (15.7%) chose surgery alone. The 5-year survival rate of these evaluated patients was 75%, 63%, and 77%, respectively (P = 0.823). Multivariate analysis revealed that normal preoperative CEA level (≦5 ng/mL) and adequate LN sampling (LN ≧ 12) were significant predictors for higher 5-year OS (P < 0.001; P = 0.007, respectively). However, the use of postoperative adjuvant chemotherapy in these N1a colon cancer patients did not significantly affect their 5-year OS.

Conclusions: A preoperative CEA level of less than or equal to 5 ng/mL, and curative surgery with an adequate lymphadenectomy determined a favorable OS outcome in stage III colon cancer with only one LN metastasis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0137053PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4575069PMC
May 2016

Cetuximab Might Be Detrimental to Metastatic Colorectal Cancer Patients with KRAS Codon 12 Mutations.

Anticancer Res 2015 Jul;35(7):4207-14

Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan, R.O.C. Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan, R.O.C. Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan, R.O.C.

Background: Anti-epidermal growth factor receptor (EGFR) monoclonal antibodies benefit patients with wild-type KRAS exon 2 metastatic colorectal cancer (mCRC). However, their effect in KRAS-mutant mCRC remains unclear.

Patients And Methods: This was a retrospective study enrolling 163 patients with unresectable KRAS-mutant mCRC diagnosed at the National Taiwan University Hospital between 2007 and 2011.

Results: The median overall survival (mOS) was 29.5 months in patients who had never used cetuximab and 19.0 months in those who had (p=0.040). The mOS was 32.0 months in patients with mutant KRAS codon 12 who had never used cetuximab and 17.5 months in those who had (p=0.017). In patients with mutant KRAS codon 13, the mOS was not significantly different. Univariate and multivariate Cox proportional hazards analysis revealed that absence of cetuximab treatment was an independent prognostic factor for longer mOS in patients with unresectable KRAS-mutant mCRC.

Conclusion: Cetuximab usage might be detrimental to patients with mCRC with mutant KRAS codon 12.
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July 2015

Prognostic Significance of CDCP1 Expression in Colorectal Cancer and Effect of Its Inhibition on Invasion and Migration.

Ann Surg Oncol 2015 Dec 28;22(13):4335-43. Epub 2015 Mar 28.

Angiogenesis Research Center, National Taiwan University, Taipei, Taiwan.

Background: To assess the correlations and functions of complement C1r/C1s, Uegf, Bmp1 domain-containing protein-1 (CDCP1) in identifying colorectal cancer (CRC) patients who are at high risk for metastasis.

Methods: Tumor specimens from 101 patients were analyzed by real-time polymerase chain reaction to detect CDCP1 expression. CDCP1 expression plasmids and shRNA were used to knock down CDCP1 expression in this study to investigate migratory and invasive abilities by Boyden chambers. The mRNA expression profiles in shCDCP1 transfectants were compared to those in control cells by conducting microarray analysis. Its downstream effectors were also invested in this study.

Results: CRC patients with a high CDCP1 expression had a statistically significant lower overall survival and disease-free survival compared to those exhibiting low CDCP1 expression. In vitro, knock-down CDCP1 expression significantly decreased migratory and invasive abilities in HCT116. Aberrant expression of CDCP1 increased cancer cell migration and invasion. By using integrated genomics, we identified ROCK1 (rho-associated, coiled-coil-containing protein kinase 1 pseudogene 1) as a downstream effector in CDCP1-mediated migration and as an invasion mediator. Clinically, ROCK1 and CDCP1 mRNA expression exhibited a strong positive correlation in CRC patient samples.

Conclusions: Our results implicated CDCP1 as a key regulator of CRC migration and invasion, and suggest that it is a useful prognostic factor for patients with CRC. Improved identification of a high-risk subset of early metastatic patients may guide indications of individualized treatment in clinical practice.
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http://dx.doi.org/10.1245/s10434-015-4505-4DOI Listing
December 2015

MicroRNA-29b regulates migration in oral squamous cell carcinoma and its clinical significance.

Oral Oncol 2015 Feb 27;51(2):170-7. Epub 2014 Nov 27.

Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University, Taipei, Taiwan; Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan; Angiogenesis Research Center, National Taiwan University, Taipei, Taiwan. Electronic address:

Objectives: MicroRNA (miRNA) machinery regulates cancer cell behavior, and has been implicated in patients' clinical status and prognosis. We found that microRNA-29b (miR-29b) increased significantly in advanced migratory cells. However, miR-29b controls the migration ability, and its regulatory mechanism in oral squamous cell carcinoma (OSCC) remains unknown.

Materials And Methods: We triggered miR-29b expression in OSCC patients and cell lines by conducting real-time quantitative PCR. We determined the functions of miR-29b in the migration of OSCC cells by using gain- and loss-of-function approaches. We elevated the target genes of miR29b through software predictions and a luciferase report assay. We used an orthotopic OSCC animal model to investigate the effects of miR29b on OSCC cell metastasis in vivo.

Results: The clinical data revealed that miR-29b expression was correlated with lymph node metastasis and an advanced tumor stage in 98 OSCC patients. Furthermore, multivariate analysis revealed that miR-29b expression was significantly correlated with recurrence, and indicated poor survival. MiR-29b promoted OSCC cell migration and downregulated CX3CL1, a cell-cell adhesion regulator, which plays an essential role in miR-29b-regulated OSCC cell migration machinery. Furthermore, we found that CX3CL1 expression was correlated with lymph node metastasis and an early tumor stage in OSCC patients, and negatively correlated with miR-29b expression.

Conclusion: MiR-29b acts as an oncomir, promoting cell migration through CX3CL1 suppression, and could be a potential therapeutic target for preventing OSCC progression.
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http://dx.doi.org/10.1016/j.oraloncology.2014.10.017DOI Listing
February 2015

Input of microenvironmental regulation on colorectal cancer: role of the CCN family.

World J Gastroenterol 2014 Jun;20(22):6826-31

Cheng-Chi Chang, Graduate Institute of Oral Biology, Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei 100, Taiwan.

Colorectal cancer (CRC) is a major health problem causing significant morbidity and mortality. Previous results from various studies indicate that CRC tumorigenicity encompasses tumor microenvironment, emphasizing the complex interacting network between cancer cells and nearby host cells, which triggers diverse signaling pathways to promote the growth and spread of cancer cells. The CCN family proteins share a uniform modular structure, mediating a variety of physiological functions, including proliferation, apoptosis, migration, adhesion, differentiation, and survival. Furthermore, CCN proteins are also involved in CRC initiation and development. Many studies have shown that CCN members, such as CCN1, CCN2, CCN3, Wnt-induced secreted protein (WISP)-1, WISP-2, and WISP-3, are dysregulated in CRC, which implies potential diagnostic markers or therapeutic targets clinically. In this review, we summarize the research findings on the role of CCN family proteins in CRC initiation, development, and progression, highlighting their potential for diagnosis, prognosis, and therapeutic application.
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http://dx.doi.org/10.3748/wjg.v20.i22.6826DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4051922PMC
June 2014

Surgical management in enterovesical fistula in Crohn disease at a single medical center.

Int Surg 2014 Mar-Apr;99(2):120-5

1 Department of Urology, National Taiwan University Hospital, Taipei, Taiwan.

Crohn disease is a chronic, transmural, inflammatory disease of the gastrointestinal tract with unknown etiology. It can affect any part of the gastrointestinal tract and may cause fistula, stricture, or abscess formation with disease progression. The preoperative diagnosis and definite management of this rare complication are challenges for physicians, urologists, and surgeons.
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http://dx.doi.org/10.9738/INTSURG-D-13-00038.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3968836PMC
June 2015