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Yung-Hung Luo,
Hsiang-Ling Ho,
Chun-Ming Tsai,
Jen-Fu Shih,
Chao-Hua Chiu,
Shinn-Liang Lai,
Yu-Chin Lee,
Reury-Perng Perng,
Jacqueline Whang-Peng, Teh-Ying Chou,
Yuh-Min Chen
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ABSTRACT: OBJECTIVES:: An increased incidence of multiple primary malignancies has been found in recent decades. However, the nature of the association between the epidermal growth factor receptor (EGFR) mutation status and multiple primary malignancies in patients with adenocarcinoma of the lungs is not clearly understood at this time. METHODS:: We retrospectively reviewed the data of our patients with adenocarcinoma of the lungs, and evaluated the association between the tumor EGFR mutation status and multiple primary malignancies. RESULTS:: From December 2008 to November 2011, 655 pulmonary adenocarcinoma patients with tumor EGFR mutation data were available for analysis. Of them, 359 had EGFR mutations (including 336 classic EGFR mutations), 63 had double primary malignancies, and 7 had triple primary malignancies. Patients with classic EGFR mutations had a higher incidence of multiple primary malignancies than those without (P=0.042). Multiple primary malignancies occurred more frequently in patients with exon 19 mutations (including insertions, point mutations, or deletions) or exon 19 deletions than in patients without (P=0.037 and 0.032, respectively). Patients with any EGFR mutations or classic EGFR mutations survived longer than those who did not (P<0.001 and <0.001, respectively). Patients with multiple primary malignancies survived for a longer period than those without (P=0.006). CONCLUSIONS:: Multiple primary malignancies occurred more frequently in patients with classic EGFR mutations, especially those with exon 19 deletions.
American journal of clinical oncology 04/2013; · 2.21 Impact Factor
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ABSTRACT: OBJECTIVE:: This study investigated the prognostic value of the new International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society (IASLC/ATS/ERS) lung adenocarcinoma classification in resected stage I lung adenocarcinoma. METHODS:: Histological classification of 283 patients undergoing surgical resection for stage I lung adenocarcinoma was determined according to the IASLC/ATS/ERS classification after comprehensive histological subtyping with recording of the percentage of each histological component (lepidic, acinar, papillary, micropapillary, and solid) in 5% increments. Their impact on overall survival, recurrence, and postrecurrence survival was investigated. RESULTS:: The 5-year overall survival and recurrence-free rates were 81.6% and 76.9%, respectively. During follow-up, 57 (20.1%) patients developed recurrence. The 2-year postrecurrence survival rate was 72.3%. The solid predominant group is associated with significant more male sex, higher smoking exposure, larger tumor size, and more poorly differentiated histological grade. Lepidic predominant group had significantly better overall survival (P = 0.002). Micropapillary and solid predominant groups had significantly lower probability of freedom from recurrence (P = 0.004). Older age (P = 0.039), visceral pleural invasion to the surface (PL2) (P = 0.009), and high grade (micropapillary/solid predominant) of the new classification (P = 0.028) were predictors of recurrence in multivariate analysis. The solid predominant group tends to have significantly worse postrecurrence survival (P = 0.074). CONCLUSIONS:: The new adenocarcinoma classification has significant impact on death and recurrence in stage I lung adenocarcinoma. Patients with PL2 and micropapillary/solid predominant pattern have significant higher risk for recurrence. This information is important for patient stratification for aggressive adjuvant chemoradiation therapy.
Annals of surgery 03/2013; · 7.90 Impact Factor
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Tzu-Chi Chen,
Yu-Wen Liu,
Yei-Hsuan Huang,
Yi-Chen Yeh, Teh-Ying Chou,
Yu-Chung Wu,
Chun-Chi Wu,
Yi-Rong Chen,
Hui-Chuan Cheng,
Pei-Jung Lu,
Jin-Mei Lai,
Chi-Ying F Huang
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ABSTRACT: The epidermal growth factor receptor (EGFR), which is up-regulated in lung cancer, involves the activation of mitogenic signals and triggers multiple signaling cascades. To dissect these EGFR cascades, we used 14 different phospho-EGFR antibodies to quantify protein phosphorylation using an in situ proximity ligation assay (in situ PLA). Phosphorylation at EGFR-Thr654 and -Ser1046 was EGF-dependent in the wild-type (WT) receptor but EGF-independent in a cell line carrying the EGFR-L858R mutation. Using a ProtoAarray™ containing ∼5000 recombinant proteins on the protein chip, we found that AURKA interacted with the EGFR-L861Q mutant. Moreover, overexpression of EGFR could form a complex with AURKA, and the inhibitors of AURKA and EGFR decreased EGFR-Thr654 and -Ser1046 phosphorylation. Immunohistochemical staining of stage I lung adenocarcinoma tissues demonstrated a positive correlation between AURKA expression and phosphorylation of EGFR at Thr654 and Ser1046 in EGFR-mutant specimens, but not in EGFR-WT specimens. The interplay between EGFR and AURKA provides an explanation for the difference in EGF dependency between EGFR-WT and EGFR-mutant cells and may provide a new therapeutic strategy for lung cancer patients carrying EGFR mutations.
PLoS ONE 01/2013; 8(3):e55657. · 4.09 Impact Factor
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ABSTRACT: PURPOSE: Erlotinib had proved efficacy in patients with advanced non-small cell lung cancer, especially adenocarcinoma. The aim of this study was to evaluate the efficacy of erlotinib in patients with advanced lung squamous cell carcinoma (LSQC). METHODS: We retrospectively reviewed medical records and serial chest images of consecutive patients who were diagnosed with advanced LSQC and had been treated with erlotinib monotherapy. The primary objective was to evaluate the treatment efficacy and to correlate with patients' clinical characteristics. RESULTS: Totally 55 patients were analyzed (42 men and 13 women, median age of 71 years). In 37 patients who had measurable lesions, 6 had partial response and 13 had stable disease, yielding an overall response rate of 16.2 % and disease control rate of 51.4 %. In all patients, the median progression-free survival (PFS) and overall survival (OS) were 2.0 months (95 % confidence interval, 1.5-2.4 months) and 10.4 months (95 % confidence interval, 0.6-20.2 months), respectively. The PFS and OS were significantly longer in patients who had good clinical response (either the tumor achieved partial response or the patients had disease controlled for more than 6 months) than those who did not (median PFS, 13.0 vs. 1.6 months; median OS, 28.3 vs. 4.9 months; both P values <0.01). Patients who never smoked seemed to have better clinical response and longer survival than those who had smoking history (P = 0.077 and 0.086, respectively). CONCLUSIONS: Erlotinib could provide some clinical benefit to patients with advanced LSQC.
Cancer Chemotherapy and Pharmacology 10/2012; · 2.83 Impact Factor
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ABSTRACT: BACKGROUND: We examined whether cigarette smoking affects the degrees of oxidative damage (8-hydroxyl-2'-deoxyguanosine [8-OHdG]) on mitochondrial DNA (mtDNA), whether the degree of 8-OHdG accumulation on mtDNA is related to the increased total mtDNA copy number, and whether human 8-oxoguanine DNA glycosylase 1 (hOGG1) Ser326Cys polymorphisms affect the degrees of 8-OHdG accumulation on mtDNA in thoracic esophageal squamous cell carcinoma (TESCC). METHODS: DNA extracted from microdissected tissues of paired noncancerous esophageal muscles, noncancerous esophageal mucosa, and cancerous TESCC nests (n = 74) along with metastatic lymph nodes (n = 38) of 74 TESCC patients was analyzed. Both the mtDNA copy number and mtDNA integrity were analyzed by quantitative real-time polymerase chain reaction (PCR). The hOGG1 Ser326Cys polymorphisms were identified by restriction fragment length polymorphism PCR and PCR-based direct sequencing. RESULTS: Among noncancerous esophageal mucosa, cancerous TESCC nests, and metastatic lymph nodes, the mtDNA integrity decreased (95.2 to 47.9 to 18.6 %; P < 0.001) and the mtDNA copy number disproportionally increased (0.163 to 0.204 to 0.207; P = 0.026). In TESCC, higher indexes of cigarette smoking (0, 0-20, 20-40, and >40 pack-years) were related to an advanced pathologic N category (P = 0.038), elevated mtDNA copy number (P = 0.013), higher mtDNA copy ratio (P = 0.028), and increased mtDNA integrity (P = 0.069). The TESCC mtDNA integrity in patients with Ser/Ser, Ser/Cys, and Cys/Cys hOGG1 variants decreased stepwise from 65.2 to 52.1 to 41.3 % (P = 0.051). CONCLUSIONS: Elevated 8-OHdG accumulations on mtDNA in TESCC were observed. Such accumulations were associated with a compensatory increase in total mtDNA copy number, indexes of cigarette smoking, and hOGG1 Ser326Cys polymorphisms.
Annals of Surgical Oncology 09/2012; · 4.17 Impact Factor
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Journal of vascular and interventional radiology: JVIR 08/2012; 23(8):1097-9. · 1.81 Impact Factor
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ABSTRACT: Previous studies using genetic-deficient murine models suggest that different T helper subsets may contribute to different types of tissue damages in graft-versus-host disease (GvHD). However, there is limited information available on the distribution of T helper cytokines in the various GvHD target tissues. In the current study, an acute GvHD murine model was setup to directly assess the in situ cytokine profiles in various GvHD tissue lesions; in addition, we also studied GvHD tissues from patients who had undergone bone marrow transplantation procedures. We observed that interferon-gamma (IFN- γ was dominant in murine liver and gastrointestinal tissue lesions, whereas IFN- γ and interleukin 17 (IL17) were abundant in murine skin lesions. Furthermore, in human GvHD tissues, interleukin 4 (IL4) and IFN- γ were predominant in liver lesions and colon lesions, respectively, while no specific cytokine was prevalent in human GvHD skin lesions. In addition, a low ratio of CD4+ T helper (Th) versusCD8+ T cytotoxic (Tc) cells in human GvHD tissue lesions, especially in the liver, was detected and this contrasts with the situation in murine GvHD tissues where CD4+ Th cells were predominant. Dual-staining for CD markers and cytokine expression showed that IFN- γ secreting T cells were enriched in all murine GvHD target tissue lesions and Tc1 and Tc2 cells were predominant in human GvHD colon and liver sections, respectively. However, IFN- γ+Th1, IL17+Th17, IFN- γ+Tc1 and IL17+Tc17 cells were slightly more frequent in human skin lesions compared to IL4+Th2 and IL4+Tc2 cells. To sum up, these results suggest that differences in cytokine imbalances may significantly contribute to tissue-specific pathogenesis in GvHD target organs and CD8+ Tc cells may play an important role in human GvHD induction.
Cell Transplantation 07/2012; · 5.13 Impact Factor
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ABSTRACT: It is of importance to search for prognostic indicators supplementing the tumour-node-metastasis stage for surgically resected early-stage lung adenocarcinomas. The roles of stromal invasion and micropapillary pattern in categorising histopathology and predicting the prognosis of stage I lung adenocarcinomas are explored.
We retrospectively examined 212 consecutive surgically resected stage I lung adenocarcinomas to propose a new histopathology-based categorical classification. Category A tumours have pure lepidic growth pattern without stromal invasion (ie, adenocarcinoma in situ). Stromal invasion in the form of central fibrotic focus is absent in category B tumours and present in category C tumours. Category B is subclassified into B1, which has areas of lepidic growth, and B2, which does not. Category C is subclassified into C1, which has invasive tumour cells in the periphery of central fibrotic focus, and C2, which has invasive tumour cells in the centre of central fibrotic focus. Based on the absence or presence of micropapillary pattern, the C2 tumours are further subclassified into C2a and C2b, respectively.
The 5-year recurrence-free probabilities for categories B1 (17 cases), B2 (10 cases), C1 (nine cases), C2a (114 cases) and C2b (62 cases) are 100%, 78.8%, 100%, 67.5% and 53.1%, respectively (p<0.001).
Based on stromal invasion and micropapillary pattern, the histopathological categorical classification proposed here provides a concise and precise scheme for outcome prediction in early-stage lung adenocarcinomas.
Journal of clinical pathology 07/2012; 65(10):910-8. · 2.43 Impact Factor
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ABSTRACT: Lung cancer is one of the most lethal malignancies worldwide, but useful biomarkers of lung cancer are still insufficient. The aim of this study is to identify some membrane-bound protein(s) associated with migration and invasion in human non-small cell lung cancer (NSCLC) cells.
We classified four NSCLC cell lines into high and low migration/invasion groups by Transwell and Matrigel assays. Using two-dimensional gel electrophoresis and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), we identified 10 membrane-associated proteins being significantly overexpressed in the high migration/invasion group. The expression of the target protein in the four NSCLC cell lines was then confirmed by reverse transcription polymerase chain reaction (RT-PCR), western blot and immunostaining. RNA interference technique was applied to observe the influence of the target protein on migration and invasion. Gelatin zymography was also performed to evaluate the activities of matrix metalloproteinase (MMP)-2 and MMP-9. Expression condition of the target protein on surgical specimens was further examined by immunohistochemical staining and the clinicopathologic data were analyzed.
We identified a mitochondria-bound protein cytochrome c oxidase subunit Va (COX Va) because of its abundant presence found exclusively in tumorous areas. We also demonstrated that migration and invasion of NSCLC cells decreased substantially after knocking down COX Va by siRNA. Meanwhile, we found a positive correlation between COX Va expression, Bcl-2 expression and activities of MMP-2 and MMP-9 in NSCLC cells. Immunohistochemical staining of surgically resected lung adenocarcinomas in 250 consecutive patients revealed that strong COX Va expression was found in 54.8% (137/250) of patients and correlated positively with the status of lymph node metastasis (P = 0.032). Furthermore, strong COX Va expression was associated with the presence of distant metastasis (P = 0.033).
Our current study showed that COX Va may play a role in migration and invasion of NSCLC cells and can be used as a biomarker to predict aggressiveness of NSCLC.
BMC Cancer 06/2012; 12:273. · 3.01 Impact Factor
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Hsin-Pai Chen,
Jeng-Kai Jiang,
Cheng-Yu Chen, Teh-Ying Chou,
Yen-Chung Chen,
Ya-Ting Chang,
Shiou-Fu Lin,
Chia-Hao Chan,
Chih-Yung Yang,
Chi-Hung Lin,
Jen-Kou Lin,
Wen-Long Cho,
Yu-Jiun Chan
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ABSTRACT: It has long been suggested that human cytomegalovirus (HCMV) might be involved in human oncogenesis. However, whether HCMV was associated with colorectal cancer (CRC) was still controversial.
To clarify whether HCMV specifically infects the tumorous tissue of CRC.
Paired tumor and adjacent non-neoplastic CRC specimens were collected from 163 patients. HCMV DNA was detected and quantified through PCR and quantitative real-time PCR. Virus location was determined by in situ hybridization (ISH) of formalin-fixed paraffin-embedded tissue sections with an HCMV-specific probe.
By PCR, HCMV DNA was detected in 42.3% (69/163) of the tumor specimens, while only 5.6%(14/163) samples of adjacent non-neoplastic tissue were positive for HCMV (p<0.0001). Quantitative real-time PCR in 54 sample pairs revealed significantly higher viral copies in the tumor specimens than the adjacent non-neoplastic tissue specimens (p<0.001). By ISH, the nucleic acids of HCMV were detected in the cytoplasm of neoplastic epithelium. No hybridization was detected in the inflammatory infiltrates, submucosa, or other stromal tissues.
HCMV preferentially infects the tumor epithelium of CRC. How the virus subsists in and interacts with the microenvironment of tumor epithelium of CRC should be studied.
Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology 05/2012; 54(3):240-4. · 3.12 Impact Factor
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ABSTRACT: This study investigated the factors predicting recurrence and death in patients with resected stage-I non-small-cell lung cancers according to the 7th edition of tumor, node, metastasis (TNM) classification for lung cancer.
All patients undergoing surgical resection for pathological stage-I non-small-cell lung cancers at Taipei Veterans General Hospital between 1980 and 2000 were retrospectively reviewed. Those undergoing sublobar resection were excluded. The factors predicting overall survival (OS), overall recurrence, local recurrence, and distant metastasis were investigated.
A total of 756 patients were eligible. The 5-year OS rate and probability of freedom from recurrence were 57.3% and 70.2%, respectively. The 2-year local-recurrence-free and distant-metastasis-free rates were 90.7% and 82.1%, respectively. In multivariable analysis, the new T descriptor (T1a, T1b, and T2a) was the common factor that significantly affected OS (p = 0.003), overall recurrence (p = 0.004), and distant metastasis (p < 0.001). Smoking index more than 20, and number of mediastinal lymph nodes dissected/sampled of 15 or fewer were common factors that significantly predicted worse OS (p < 0.001, p < 0.001, respectively), lower probability of freedom from overall recurrence (p = 0.025, p = 0.009, respectively), and higher risk of local recurrence (p < 0.001, p = 0.030, respectively). Non-squamous-cell histology predicted higher risk of distant metastasis (p = 0.006).
Risks of death and recurrence increase as the T descriptor upgrades in the new TNM system. The combination of risk factors can be used to identify high-risk subgroups of local recurrence and distant metastasis.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 05/2012; 7(7):1115-23. · 4.55 Impact Factor
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ABSTRACT: We investigated the microsatellite alterations in mitochondrial DNA (mtDNA) and in TP53 in thoracic esophageal squamous cell carcinomas (TESCC). Using laser microdissection, 66 paired non-cancerous esophageal muscles, non-cancerous esophageal mucosa, cancerous TESCC nests plus 35 metastatic lymph nodes harvested from 66 resected esophagi of TESCC patients were subjected to DNA extraction. D310 and D17S960 were chosen as markers to address microsatellite alterations in mtDNA, including changes in copy number and homoplasmic/heteroplasmic mutations of mtDNA, and in TP53, including loss of heterozygosity (LOH) and microsatellite instability (MI). From non-cancerous esophageal mucosa to cancerous TESCC nests and then metastatic lymph nodes, a trend of homoplasmic D310 mutation (10.6, 25.8, 31.4%; p=0.023), an ever increase of mtDNA copy ratios (0.892, 1.128, 1.183; p=0.018) and an elevated incidence of TP53 LOH (19.7, 34.8, 37.1%; p=0.010) were observed. From T1, T2, T3 to T4 TESCC, the incidence of TP53 LOH (12.5, 16.7, 34.8, 52.2%; p=0.011) was increased, in a stepwise fashion. Furthermore, we observed an association of TP53 LOH with an increased mtDNA copy ratio (p=0.022) and TP53 MI with heteroplasmic D310 mutation (p=0.069) in TESCC. Concurrent and associated microsatellite alterations in mtDNA and in TP53 in TESCC support the cancer clonal expansion theory and imply a possible relationship between the mitochondria and p53 in TESCC.
Oncology Reports 04/2012; 28(1):69-76. · 1.84 Impact Factor
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ABSTRACT: Tumor-associated macrophages (TAMs) are the major component of tumor-infiltrating leukocytes. TAMs are heterogeneous, with distinct phenotypes influenced by the microenvironment surrounding tumor tissues. Decoy receptor 3 (DcR3), a member of the TNFR superfamily, is overexpressed in tumor cells and is capable of modulating host immunity as either a neutralizing decoy receptor or an effector molecule. Upregulation of DcR3 has been observed to correlate with a poor prognosis in various cancers. However, the mechanisms underlying the DcR3-mediated tumor-promoting effect remain unclear. We previously demonstrated that DcR3 modulates macrophage activation toward an M2-like phenotype in vitro and that DcR3 downregulates MHC class II expression in TAMs via epigenetic control. To investigate whether DcR3 promotes tumor growth, CT26-DcR3 stable transfectants were established. Compared with the vector control clone, DcR3-transfectants grew faster and resulted in TAM infiltration. We further generated CD68 promoter-driven DcR3 transgenic (Tg) mice to investigate tumor growth in vivo. Compared with wild-type mice, macrophages isolated from DcR3-Tg mice displayed higher levels of IL-10, IL-1ra, Ym1, and arginase activity, whereas the expression of IL-12, TNF-α, IL-6, NO, and MHC class II was downregulated. Significantly enhanced tumor growth and spreading were observed in DcR3-Tg mice, and the enhanced tumor growth was abolished by arginase inhibitor N-ω-hydroxy-l-norarginine and histone deacetylase inhibitor sodium valproate. These results indicated that induction of TAMs is an important mechanism for DcR3-mediated tumor progression. Our findings also suggest that targeting DcR3 might help in the development of novel treatment strategies for tumors with high DcR3 expression.
The Journal of Immunology 03/2012; 188(5):2464-71. · 5.79 Impact Factor
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ABSTRACT: Tumor epidermal growth factor receptor (EGFR) mutation analysis is significant for making treatment decisions for metastatic pulmonary adenocarcinoma. However, less than half of patients have adequate tumor samples for mutation analysis. Patients with adenocarcinoma of the lungs who were due to receive erlotinib treatment were included in the present study. Tumor EGFR mutation status was analyzed using DNA sequencing. Plasma specimens from the patients were collected prior to erlotinib treatment. The plasma-free DNA EGFR mutation status was analyzed using the PCR clamp method. A total of 54 consecutive patients were included in the study. The plasma-free DNA EGFR mutation status of the 54 patients was analyzed. Only 30 patients had adequate tumor samples for EGFR analysis, including 15 with activating mutations (exon 19 deletions or L858R). EGFR-activating mutations were detected in the plasma-free DNA in 25 of 54 patients. The response rate was 86.7 and 33.3% in patients with and without tumor activating mutations, respectively (p=0.002). The response rate was 68 and 31% based on the patients' plasma-free DNA EGFR mutation status, respectively (p=0.013). No significant difference in progression-free survival (PFS) was observed between patients with and without EGFR-activating mutations, according to data from tumor tissue or plasma-free DNA analysis, although the median PFS time was longer for those patients with EGFR-activating mutations in plasma samples. Plasma EGFR mutation analysis is useful for adenocarcinoma patients who have no or inadequate tumor samples available for EGFR examination. Patients with plasma EGFR-activating mutations had an improved response rate and a statistically insignificant longer PFS.
Oncology letters 03/2012; 3(3):713-717. · 0.11 Impact Factor
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ABSTRACT: Visceral pleural invasion (VPI) has been defined as invasion of the tumor beyond the elastic layer (PL1), including invasion to the visceral pleural surface (PL2). The aim of this study was to evaluate the prognostic factors and patterns of recurrence in resected node-negative non-small cell lung cancer (NSCLC) with VPI.
We retrospectively reviewed the clinicopathologic characteristics of 355 patients with resected node-negative NSCLC with VPI at Taipei Veterans General Hospital between 1990 and 2006. The prognostic value and patterns of recurrence were analyzed and compared between PL1 and PL2 groups.
The median follow-up time was 54.2 months. The 5-year overall survival rate and probability of freedom from recurrence were 61.9% and 66.2%, respectively. The extent of VPI was PL1 in 300 patients (84.5%) and PL2 in 55 (15.5%). During follow-up, 107 patients (30.1%) developed recurrence. The patterns of recurrence included local recurrence only in 20 patients (18.7%), distant metastasis only in 59 (55.1%), and both local recurrence and distant metastasis in 28 (26.2%). Thirteen of the 107 patients (12.1%) with recurrence developed malignant pleural effusion. The percentage of malignant pleural effusion in the PL2 group was significantly higher than that in the PL1 group (P = .006). Patients with PL2 had significantly worse overall survival (P = .046) and lower probability of freedom from recurrence (P = .028) in multivariate analysis.
PL2 was a significant prognostic factor for recurrence and worse overall survival in node-negative NSCLC with VPI. This information is important for further design of clinical trials for aggressive adjuvant therapy.
Chest 01/2012; 142(1):141-50. · 5.25 Impact Factor
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Di-Cing Wei,
Yi-Chen Yeh,
Jung-Jyh Hung, Teh-Ying Chou,
Yu-Chung Wu,
Pei-Jung Lu,
Hui-Chuan Cheng,
Yu-Lin Hsu,
Yu-Lun Kuo,
Kuan-Yu Chen,
Jin-Mei Lai
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ABSTRACT: Tumor recurrence is the most common cause of disease failure after surgical resection in early-stage lung adenocarcinoma. Identification of clinically relevant prognostic markers could help to predict patients with high risk of disease recurrence. A meta-analysis of available lung adenocarcinoma microarray datasets revealed that T-LAK cell-originated protein kinase (TOPK), a serine/threonine protein kinase, is overexpressed in lung cancer. Using stable cell lines with overexpression or knockdown of TOPK, we have shown that TOPK can promote cell migration, invasion, and clonogenic activity in lung cancer cells, suggesting its crucial role in lung tumorigenesis. To evaluate the prognostic value of TOPK expression in resected stage I lung adenocarcinoma, a retrospective analysis of 203 patients diagnosed with pathological stage I lung adenocarcinoma was carried out to examine the expression of TOPK by immunohistochemistry (IHC). The prognostic significance of TOPK overexpression was examined. Overexpression of TOPK (IHC score >3) was detected in 67.0% of patients, and these patients were more frequently characterized with disease recurrence and angiolymphatic invasion. Using multivariate analysis, patient age (>65 years old; P = 0.002) and TOPK overexpression (IHC score >3; P < 0.001) significantly predicted a shortened overall survival. Moreover, TOPK overexpression (IHC score >3; P = 0.005) also significantly predicted a reduced time to recurrence in the patients. Our results indicate that overexpression of TOPK could predetermine the metastatic capability of tumors and could serve as a significant prognostic predictor of shortened overall survival and time to recurrence.
Cancer Science 12/2011; 103(4):731-8. · 3.33 Impact Factor
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ABSTRACT: The primary objective of this study was to compare the response rates of elderly, chemonaive patients with advanced non-small cell lung cancer (NSCLC) treated with daily oral erlotinib versus oral vinorelbine.
Chemonaive Taiwanese patients aged 70 years or older who had advanced NSCLC were randomized to receive either oral erlotinib 150 mg (E) daily or oral vinorelbine 60 mg/m (V) on days 1 and 8 every 3 weeks.
From February 2007 to July 2008, 116 patients were enrolled and 113 were included in the intent-to-treat population: 57 patients in the E group and 56 patients in the V group. Objective response rates were 22.8% (13 of 57) in E and 8.9% (5 of 56) in V (p = 0.0388). Median progression-free survival (PFS) was 4.57 months in E and 2.53 months in V (p = 0.0287), with an 80.6% increase in median PFS for E compared with V. Median survival time was 11.67 months in E and 9.3 months in V (p = 0.6975). Toxicities were generally mild in both groups. Median PFS was longest for epidermal growth factor receptor gene (EGFR)-mutated patients in the E group, followed by EGFR-mutated patients in V, EGFR wild type in E, and EGFR wild type in V (p = 0.0034). Overall survival was longer for EGFR-mutated patients than for EGFR wild-type patients (p < 0.0001).
Erlotinib is highly effective compared with oral vinorelbine in elderly, chemonaive, Taiwanese patients with NSCLC. EGFR-mutated patients had better survival than those with EGFR wild-type disease, regardless of the treatment received.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 12/2011; 7(2):412-8. · 4.55 Impact Factor
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ABSTRACT: Esophageal squamous cell carcinoma (ESCC) is a lethal malignancy, but only limited molecular markers can predict its prognosis. Recently, a DNA double-strand break repair protein Nijmegen breakage syndrome 1 (NBS1) was reported to induce Snail expression and predict poor prognosis in head and neck cancers. However, the clinicopathologic roles of NBS1 and Snail in ESCC remain unclear.
From January 1995 to September 1999, tissue samples from 153 patients with ESCC who underwent esophagectomies at our institutions were collected and made into tissue core arrays for study. Expression of NBS1 and Snail was examined by immunohistochemical staining. The clinicopathologic data were analyzed, and some additional studies were performed to explore the relationship between NBS1 and Snail.
NBS1 overexpression was observed in 28.1% (43/153) of ESCC, whereas Snail overexpression was observed in 26.1% (40/153) of ESCC. Overexpression of NBS1 correlated inversely with nodal status (P = 0.009) and was associated with better overall survival (P = 0.002). On the other hand, overexpression of Snail correlated positively with lymphovascular invasion (P = 0.034) and was associated with worse overall survival (P = 0.036). Meanwhile, NBS1 overexpression correlated inversely with Snail overexpression marginally (P = 0.084). Using the Cox regression analysis, T status (P = 0.006), M status (P = 0.008), and NBS1 overexpression (P = 0.007) were the independent factors of overall survival.
Our results showed that NBS1 overexpression was an independent factor of better survival and Snail overexpression predicted a worse survival in ESCC. Combination of NBS1 plus Snail expression status could be used as a predictor of prognosis in ESCC.
Annals of Surgical Oncology 09/2011; 19 Suppl 3:S549-57. · 4.17 Impact Factor
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ABSTRACT: Although both leukopenia and thrombocytopenia are not uncommon hematological findings among patients with novel 2009 H1N1 influenza virus infection, immune thrombocytopenic purpura has rarely been shown to be associated with this novel influenza A infection. Here, we describe a previously healthy adolescent who presented with fever, influenza-like symptoms and acute onset of generalized petechiae and active oral mucosa bleeding on the third day of his illness. Severe leukopenia and thrombocytopenia were found. There was neither malignancy nor blast cells found by bone marrow aspiration. Real-time reverse transcriptase polymerase chain reaction was positive for novel 2009 H1N1 influenza infection. Novel influenza-associated atypical immune thrombocytopenic purpura was diagnosed. The patient recovered uneventfully after oseltamivir and methylprednisolone therapy.
Journal of the Chinese Medical Association 09/2011; 74(9):425-7. · 0.79 Impact Factor
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ABSTRACT: Previous studies have shown that lung squamous cell carcinoma has higher ¹⁸F-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET) than adenocarcinoma. We hypothesized that histological subtypes of lung adenocarcinoma were also different in ¹⁸F-FDG uptake.
Patients who had preoperative PET/computed tomography (CT) scan and had undergone complete resection for lung adenocarcinoma between April 2007 and December 2009 were enrolled in this study. Because of the limitation of spatial resolution on PET/CT, tumors less than 1 cm were excluded for analysis. Two independent classification systems were used to categorize histological subtypes of adenocarcinoma; one was modified from the current World Health Organization classification and the other used the morphological features of the terminal respiratory unit (TRU). The maximal standardized uptake value (SUVmax) on PET/CT and the glucose transporter type 1 (GLUT-1) expression of the tumors were measured and correlated to the histology of lung adenocarcinoma.
One hundred fifty-two patients with 153 primary lung adenocarcinomas were included. There was a significant difference in SUVmax among different histological subtypes. Namely, solid predominant adenocarcinomas had significantly higher SUVmax than those with other predominant histology (p < 0.001), and TRU-type adenocarcinomas had significantly lower SUVmax than non-TRU-type adenocarcinomas (p < 0.001). Consistently, GLUT-1 expression was higher in tumors with a solid growth pattern than those without (p < 0.001) and in tumors with non-TRU type than TRU type (p < 0.001).
The histological subtypes of lung adenocarcinomas differ in GLUT-1 expression and ¹⁸F-FDG uptake on the PET/CT scan, suggesting that histological subtyping not only has morphological but also biological implications.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 08/2011; 6(10):1697-703. · 4.55 Impact Factor
