Hee-Jin Jang

University of Texas MD Anderson Cancer Center, Houston, Texas, United States

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Publications (13)52.31 Total impact

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    ABSTRACT: Purpose: The Hippo pathway is a tumor suppressor in the liver. However, the clinical significance of Hippo pathway inactivation in HCC is not clearly defined. We analyzed genomic data from human and mouse tissues to determine clinical relevance of Hippo pathway inactivation in HCC. Experimental design: We analyzed gene expression data from Mst1/2-/- and Sav1-/- mice and identified a 610-gene expression signature reflecting Hippo pathway inactivation in the liver (silence of Hippo [SOH] signature). By integrating gene expression data from mouse models with those from human HCC tissues, we developed a prediction model that could identify HCC patients with an inactivated Hippo pathway and used it to test its significance in HCC patients, via univariate and multivariate Cox analyses. Results: HCC patients (National Cancer Institute cohort, n = 113) with the SOH signature had a significantly poorer prognosis than those without the SOH signature (P < 0.001 for overall survival [OS]). The significant association of the signature with poor prognosis was further validated in the Korean (n=100, P = 0.006 for OS) and Fudan University cohorts (n=242, P = 0.001 for OS). On multivariate analysis, the signature was an independent predictor of recurrence-free survival (hazard ratio, 1.6; 95% confidence interval, 1.12-2.28: P = 0.008). We also demonstrated significant concordance between the SOH HCC subtype and the hepatic stem cell HCC subtype that had been identified in a previous study (P < 0.001). Conclusions: Inactivation of the Hippo pathway in HCC is significantly associated with poor prognosis.
    Clinical Cancer Research 10/2015; DOI:10.1158/1078-0432.CCR-15-1447 · 8.72 Impact Factor
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    ABSTRACT: Metabolic activation is a common feature of many cancer cells and is frequently associated with the clinical outcomes of various cancers, including hepatocellular carcinoma (HCC). Thus, aberrantly activated metabolic pathways in cancer cells are attractive targets for cancer therapy. YAP1 and TAZ are oncogenic downstream effectors of the Hippo tumor suppressor pathway, which is frequently inactivated in many cancers. Our study revealed that YAP1/TAZ regulates amino acid metabolism by up-regulating expression of the amino acid transporters SLC38A1 and SLC7A5. Subsequently, increased uptake of amino acids by the transporters activates mTORC1, a master regulator of cell growth, and stimulates cell proliferation. We also show that high expression of SLC38A1 and SLC7A5 is significantly associated with shorter survival in HCC patients. Furthermore, inhibition of the transporters and mTORC1 significantly block YAP1/TAZ-mediated tumorigenesis in the liver. These findings elucidate regulatory networks connecting the Hippo pathway to mTORC1 through amino acid metabolism and the mechanism's potential clinical implications for treating HCC. Conclusion: YAP1 and TAZ regulate cancer metabolism and mTOCR1 through regulation of amino acid transportation and two amino acid transporters, SLC38A1 and SLC7A5, might be important therapeutic targets. This article is protected by copyright. All rights reserved.
    Hepatology 09/2015; DOI:10.1002/hep.28223 · 11.06 Impact Factor
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    ABSTRACT: nc886 (= vtRNA2-1 or pre-miR-886) is a recently discovered noncoding RNA that is a cellular PKR (Protein Kinase RNA-activated) ligand and repressor. nc886 has been suggested to be a tumor suppressor, solely based on its expression pattern and genomic locus. In this report, we have provided sufficient evidence that nc886 is a putative tumor suppressor in esophageal squamous cell carcinoma (ESCC). In 84 paired specimens from ESCC patients, nc886 expression is significantly lower in tumors than their normal adjacent tissues. More importantly, decreased expression of nc886 is significantly associated with shorter recurrence-free survival of the patients. Suppression of nc886 is mediated by CpG hypermethylation of its promoter, as evidenced by its significant negative correlation to nc886 expression in ESCC tumors and by induced expression of nc886 upon demethylation of its promoter. Knockdown of nc886 and consequent PKR activation induce FOS and MYC oncogenes as well as some inflammatory genes including oncogenic NF-κB. When ectopically expressed, nc886 inhibits proliferation of ESCC cells, further demonstrating that nc886 could be a tumor suppressor. All these findings implicate nc886 as a novel, putative tumor suppressor that is epigenetically silenced and regulates the expression of oncogenes in ESCC.
    Oncotarget 06/2014; 5(11):3472-3481. DOI:10.18632/oncotarget.1927 · 6.36 Impact Factor
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    ABSTRACT: Purpose After esophagectomy and gastric reconstruction for esophageal cancer, patients suffer from various symptoms that can detract from quality of life. Endoscopy is a useful diagnostic tool for evaluating patients after esophagectomy. This observational study was performed to investigate the correlation between symptoms and endoscopic findings one year after esophageal surgery and to assess the clinical usefulness of one-year endoscopic follow-up. Materials and Methods From 2001 to 2008, 162 patients who underwent esophagectomy with gastric reconstruction were endoscopically examined one year after operation. Results Patients suffered from the following symptoms: nocturnal cough (n=10), regurgitation (n=7), cervical heartburn (n=3), lump sensation (n=2), dysphagia (n=20) and odynophagia (n=22). Eighty-five (52.5%) patients had abnormal findings on endoscopic examination. Twelve (7.4%) patients had reflux esophagitis, and 37 (22.8%) patients had an anastomotic stricture. Only stricture-related symptoms were correlated with the finding of anastomotic strictures (p<0.001). Two patients had recurrences at the anastomotic sites, and four patients had regional lymph node recurrences with gastric conduit invasion visualized by endoscopy. Newly-developed malignancies in the esophageal remnant or hypopharynx that were not detected by clinical symptoms and imaging studies were reported in two patients. Conclusion One year after esophagectomy, endoscopic findings were not correlated with clinical symptoms, except those related to stricture. Routine endoscopic follow-up is a useful tool for identifying latent functional and oncological lesions.
    Yonsei medical journal 03/2013; 54(2):381-8. DOI:10.3349/ymj.2013.54.2.381 · 1.29 Impact Factor
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    ABSTRACT: MicroRNAs (miRNAs) are widely known for their function as regulators of gene expression via translational repression. Polymorphisms in miRNAs have been shown to affect the regulatory capacity of miRNAs by influencing miRNA processing and/or miRNA-mRNA interactions. The purpose of this study was to investigate the association between 7 single nucleotide polymorphisms (SNPs) commonly found in precursor miRNA (pre-miRNA) and primary miRNA (pri-miRNA) sequences and the recurrence of disease in patients who underwent a complete resection of non-small cell lung cancer (NSCLC). Five SNPs found in pre-miRNAs (rs11614913/miR-196a2, rs2910164/miR-146a, rs6505162/miR-423, rs2289030/miR-492, and rs895819/miR-27a) and 2 SNPs found in pri-miRNAs (rs7372209/miR-26a-1 and rs213210/miR-219-1) were genotyped in 388 patients with NSCLC. Among 388 patients, variants of the rs2910164 SNP were significantly associated with recurrence-free survival (RFS) (P = .016, log-rank test). When the results were subdivided by the tumor stage, variants of the rs2910164 and rs11614913 SNPs positively correlated with a better RFS (adjusted hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.28-0.80; adjusted HR, 0.60; 95% CI, 0.38-0.94, respectively) in patients with stage II and stage III disease. Moreover, RFS significantly improved in patients with higher numbers of variant alleles in the rs2910164 and rs11614913 SNPs. Our findings suggest that polymorphisms in the rs2910164 of miR-146a and the rs11614913 of miR-196a2 are associated with prognosis in patients with completely resected NSCLC.
    The Journal of thoracic and cardiovascular surgery 07/2012; 144(4):794-807. DOI:10.1016/j.jtcvs.2012.06.030 · 4.17 Impact Factor
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    Seong Yong Park · Hyun-Sung Lee · Hee-Jin Jang · Jungnam Joo · Jae Ill Zo ·
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    ABSTRACT: Objectives: Respiratory failure from acute lung injury (ALI), acute respiratory distress syndrome (ARDS) and pneumonia are the major cause of morbidity and mortality following an oesophagectomy for oesophageal cancer. This study was performed to investigate whether an intraoperative corticosteroid can attenuate postoperative respiratory failure. Methods: Between November 2005 and December 2008, 234 consecutive patients who underwent an oesophagectomy for oesophageal cancer were reviewed. A 125-mg dose of methylprednisolone was administered after performing the anastomosis. ALI, ARDS and pneumonia occurring before postoperative day (POD) 7 were regarded as acute respiratory failure. Result: The mean age was 64.2 ± 8.7 years. One hundred and fifty-one patients were in the control group and 83 patients in the steroid group. Patients' characteristics were comparable. The incidence of acute respiratory failure was lower in the steroid group (P = 0.037). The incidences of anastomotic leakage and wound dehiscence were not different (P = 0.57 and P = 1.0). The C-reactive protein level on POD 2 was lower in the steroid group (P < 0.005). Multivariate analysis indicates that the intraoperative steroid was a protective factor against acute respiratory failure (P = 0.046, OR = 0.206). Conclusions: Intraoperative corticosteroid administration was associated with a decreased risk of acute respiratory failure following an oesophagectomy. The laboratory data suggest that corticosteroids may attenuate the stress-induced inflammatory responses after surgery.
    Interactive Cardiovascular and Thoracic Surgery 06/2012; 15(4):639-43. DOI:10.1093/icvts/ivs167 · 1.16 Impact Factor
  • Hyun-Sung Lee · Hee-Jin Jang ·
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    ABSTRACT: Mediastinal lymph node staging is an important component of the assessment and management of patients with operable non-small cell lung cancer and is necessary to achieve complete resection. During minimally invasive surgery, performance of an equivalent oncologic resection, including adequate lymph node dissection similar in extent to open thoracotomy, is absolutely necessary. We describe our techniques for video-assisted thoracic surgery (VATS) and Robot-assisted VATS (R-VATS) mediastinal lymph node dissection when performing thoracoscopic lobectomy for lung cancer. Between 2008 and 2011, 200 consecutive patients who underwent VATS or R-VATS lobectomies for early stage lung cancer were analyzed. In our series, we removed about 25 lymph nodes per case in both complete VATS and R-VATS. A thorough lymph node dissection in lung cancer is possible with either VATS or R-VATS technique without oncological compromise.
    Seminars in Thoracic and Cardiovascular Surgery 06/2012; 24(2):131-41. DOI:10.1053/j.semtcvs.2012.02.004
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    ABSTRACT: Pharyngo-esophageal reconstruction using free jejunal grafts (FJGs) has been widely used, but the procedure is technically demanding and requires the involvement of multiple departments. We performed simplified reconstruction with FJGs using end-to-side vascular anastomosis and extended pharyngo-jejunostomy. The jejunal artery and vein were anastomosed to the neck vessels in an end-to-side fashion without microvascular anastomosis. Pharyngo-jejunostomy with extended end-to-end anastomosis was performed to reduce size mismatch. We retrospectively analyzed the medical records of 32 patients diagnosed with pharyngeal, esophageal, or pyriform sinus cancer who received a FJG. The mean age was 61.5±9.4 years, and there were 25 male patients. Jejunal vessels were commonly anastomosed to the right common carotid artery and the right internal jugular vein (22, 68.8%). The mean ischemic times of the FJG and carotid artery clamping time were 46.5±8.1 and 15.8±4.4 minutes, respectively. During the procedure, 3 patients suffered from inadequate reperfusion of the FJG requiring removal of the initial graft and replacement with another FJG. There were no neurologic complications, postoperative deaths, or adverse events directly related to FJG except for leakage of the pharyngo-jejunostomy site in 1 patient, which was primarily repaired. During the follow-up period, 5 patients (15.6%) suffered from dysphagia, but only 3 patients had evidence of anastomotic strictures at the jejuno-esophagostomy site. Thirteen patients (40.6%) received postoperative adjuvant radiotherapy. Our technique of FJG with end-to-side vascular anastomosis and extended pharyngo-jejunostomy is simple and safe.
    The Annals of thoracic surgery 03/2012; 93(6):1850-4. DOI:10.1016/j.athoracsur.2012.01.068 · 3.85 Impact Factor
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    ABSTRACT: Sleeve lobectomy was introduced for patients with lung cancer whose pulmonary reserve was inadequate for pneumonectomy. However, the safety and survival benefits of wedge bronchoplastic lobectomy as an alternative to sleeve lobectomy have not been thoroughly studied. This study was performed to evaluate the safety and oncologic results of wedge bronchoplastic lobectomy for lung cancer. We retrospectively analyzed 191 patients who underwent wedge bronchoplastic lobectomy and mediastinal lymph node dissection from 2001 to 2009. There were 174 male patients with a mean age of 61.8 ± 8.2 years. The median follow-up duration was 28 months. Nine patients showed severe postoperative complications: bronchopleural fistulas (n = 3), necrosis at the bronchoplasty site (n = 1), or obstruction (n = 5). The operative mortality rate was 3.7%. Local and regional recurrences were reported in 17 and 12 patients, respectively. The 5-year overall survival was 62.8%. The 5-year overall survival was 68.6% in N0, 64.4% in N1, and 52.6% in N2 (P = .09). The 5-year overall freedoms from local recurrence and locoregional recurrence were 85.3% and 78.9%, respectively, which did not differ by nodal status. A multivariate analysis showed that positive N1 and N2 nodes were risk factors (P = .036 and P = .042, respectively) for overall survival after wedge bronchoplastic lobectomy. Wedge bronchoplastic lobectomy for lung cancer is a safe and feasible procedure that does not compromise oncologic principles. It can be considered an appropriate alternative to sleeve lobectomy and pneumonectomy, regardless of nodal status.
    The Journal of thoracic and cardiovascular surgery 11/2011; 143(4):825-831.e3. DOI:10.1016/j.jtcvs.2011.10.057 · 4.17 Impact Factor
  • Hee-Jin Jang · Hyun-Sung Lee · Seong Yong Park · Jae Ill Zo ·
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    ABSTRACT: : Robotic surgery has evolved in urology, gynecology, and general surgery and seems to be an oncologically sound surgical approach. Robotic surgery has been infrequently reported for pulmonary lobectomy. The aim of this study is to compare the outcomes of our early experience in performing robot-assisted lobectomy (RAL) with video-assisted thoracic surgery (VATS) for the treatment of non-small cell lung cancer. : Between February and October 2009, 40 patients underwent RAL for resectable non-small cell lung cancer. The dissection and anatomic isolation of the hilar structures were performed using two arms of the da Vinci S system. A retrospective comparison with two VATS groups was performed, our initial 40 VATS patients (between January 2006 and February 2007) and our most recent 40 VATS patients (between June 2008 and September 2009). The entire experience with VATS lobectomy is 163 cases. : In the RAL group, the mean age was 64 years, and there were 23 male patients. Adenocarcinoma was diagnosed in 29 patients with a mean tumor size of 3.5 cm. There were no conversions to open thoracotomy. Among the patients in our initial and recent VATS lobectomy groups, the conversion rate was 3 (8%) and 2 (5%) patients, respectively. The operative time for the RAL (240 ± 62 minutes) and the initial VATS lobectomy groups (257 ± 57 minutes) were similar but was longer than the recent VATS lobectomy group (161 ± 39 minutes, P < 0.001). However, the rate of postoperative complications in the RAL group (n = 4, 10%) was significantly lower than that of the initial VATS group (n = 13, 32.5%, P = 0.027) and similar to that of the recent VATS group (n = 7, 17.5%, P = 0.755). Intraoperative bleeding was reduced in the RAL group compared with the initial VATS group (219 mL vs 374 mL P = 0.017), and the median length of postoperative stay was significantly shorter for the RAL group compared with the initial VATS group (6 vs 9 days, P < 0.001). : The outcomes of our early RAL experience was comparable to the our outcomes achieved with VATS lobectomy, whether performed early or late.
    Innovations Technology and Techniques in Cardiothoracic and Vascular Surgery 09/2011; 6(5):305-10. DOI:10.1097/IMI.0b013e3182378b4c
  • Hee-Jin Jang · Hyun-Sung Lee · Moon Soo Kim · Jong Mog Lee · Jae Ill Zo ·
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    ABSTRACT: This study evaluated the clinical results, nodal metastatic patterns, and overall efficacy of esophagectomy with three-field lymph node dissection for upper esophageal squamous cell carcinoma (SCC). Between 2001 and 2008, esophagectomy was performed in 497 esophageal cancer patients, of whom 93 underwent esophagectomy with three-field lymph node dissection, without neoadjuvant treatment for upper esophageal SCC. Of these 93 patients, 91 (97.8%) were men, the median age was 65.0 years, and 82 (88.2%) underwent R0 resection with curative intent. In-hospital mortality was 4.3%. Pathologic T N M stages were stage I, 8.6%; stage II, 16.1%; stage III, 75.3%; and stage IV, 0%. The mean numbers of total lymph nodes dissected and, of those, total metastatic lymph nodes per patient were 61.7±18.2 and 4.7±7.0, respectively. Metastases occurred to the recurrent laryngeal lymph nodes in 43.3%, to the cervical lymph nodes in 46.2%, and to abdominal lymph nodes in 24.7% of patients. Overall 5-year and disease-free survival rates were 43.5% and 34.3%, respectively, and were 50.1% and 37.6%, respectively, for R0 resection. Recurrent laryngeal lymph node chains are those most commonly affected by nodal metastasis, and the prevalence of cervical lymph node involvement is high, at more than 40%. Esophagectomy with three-field lymph node dissection in patients with upper esophageal SCC can be performed with acceptable morbidity and mortality. Curative R0 resection for upper esophageal SCC achieved a satisfactory 5-year survival rate.
    The Annals of thoracic surgery 06/2011; 92(3):1091-7. DOI:10.1016/j.athoracsur.2011.03.093 · 3.85 Impact Factor
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    ABSTRACT: In stage IA non-small cell lung cancer (NSCLC), lobectomy and mediastinal lymph node dissection is considered the standard treatment. However, 20% to 30% of patients have cancer recurrences. The purpose of this study was to determine the patterns and risk factors for recurrence in patients with stage IA NSCLC. We retrospectively reviewed the medical records of 201 patients who had confirmed stage IA NSCLC by lobectomy and complete lymph node dissection. There were 131 male patients with a mean age of 60.68±9.26 years. The median follow-up period was 41.4 months. Recurrences were reported in 16 patients. One hundred fourteen and 87 patients were T1a (≤2 cm) and T1b (>2 cm to ≤3 cm), respectively. The pathologic results were as follows: adenocarcinomas and bronchioloalveolar carcinomas (n=134); squamous cell carcinomas (n=57); and other diagnoses (n=10). Tumor necrosis and lymphatic invasion were significant adverse risk factors for recurrence based on univariate analysis. Multivariate analysis showed that tumor necrosis was the only significant risk factor to predict cancer recurrence (hazard ratio, 4.336; p=0.032). The 5-year overall survival was 94.8% for necrosis-negative patients and 86.2% for necrosis-positive patients (p=0.04). The 5-year disease-free survival was 92.1% for necrosis-negative patients and 78.9% for necrosis-positive patients (p=0.016). Tumor necrosis was shown to be an adverse risk factor for survival and recurrence in patients with stage IA NSCLC. Thus, close observation and individualized adjuvant therapy might be helpful for patients with stage IA NSCLC with tumor necrosis.
    The Annals of thoracic surgery 06/2011; 91(6):1668-73. DOI:10.1016/j.athoracsur.2010.12.028 · 3.85 Impact Factor
  • Hyun-Sung Lee · Hee-Jin Jang ·

    The Annals of thoracic surgery 03/2011; 91(3):878-9. DOI:10.1016/j.athoracsur.2010.11.054 · 3.85 Impact Factor

Publication Stats

107 Citations
52.31 Total Impact Points


  • 2013-2015
    • University of Texas MD Anderson Cancer Center
      • Department of Systems Biology
      Houston, Texas, United States
  • 2011-2012
    • National Cancer Center Korea
      • Lung Cancer Branch
      Kōyō, Gyeonggi-do, South Korea