[Show abstract][Hide abstract] ABSTRACT: The protein β-catenin exhibits a dual function in cells, by acting as a major structural component of cell-cell adherens junctions and as a central signaling molecule in the Wnt signaling pathway. However, how the regulation of β-catenin expression during tumor metastasis in non-small cell lung cancer (NSCLC) varies according to histological type remains unclear. To investigate the regulatory mechanism of β-catenin on tumor metastasis, the present study compared the expression of Wnt1, β-catenin and E-cadherin in 41 primary NSCLC tumors and their corresponding metastatic lesions by immunohistochemistry. Altered expression of β-catenin was more frequent in the metastatic tumors (34/41, 82.9%) than in the corresponding primary tumors (24/41, 58.5%; P<0.05). There were 12 cases [nine of adenocarcinoma (ADC) and three of squamous cell carcinoma (SqCC)] that revealed discordant β-catenin expression between the primary tumors and the corresponding metastatic lesions. Of these, 11 cases (11/12, 91.7%; nine ADCs and two SqCCs) demonstrated acquired β-catenin alterations in the metastatic lesions. Subgroup analysis of these nine ADCs revealed that six cases (6/9, 66.7%) were accompanied by E-cadherin loss but no Wnt1 overexpression. Subgroup analysis of the three SqCCs revealed discordant β-catenin expression. Two cases (2/3, 66.7%) demonstrated acquired β-catenin expression during metastatic progression with Wnt1 overexpression but no change in E-cadherin expression. One case of SqCC revealed normal β-catenin expression in the metastasis although the expression was aberrant in the primary tumor. The results of the present study revealed that the changes in β-catenin expression occurred during tumor metastasis by different mechanisms, depending on histological type. The alterations in β-catenin expression may be regulated by a cadherin-catenin system in ADCs with reduced membranous expression of E-cadherin, but mediated by Wnt1 overexpression in SqCCs with cytoplasmic or nuclear transition types.
Experimental and therapeutic medicine 02/2015; 9(2):311-318. · 0.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: ROS1 has attracted much attention as a possible oncogenic driver and ROS1-rearranged tumors show sensitivity to most ALK inhibitors. We aimed to clarify the prevalence of ROS1 gene rearrangement and investigate the clinical implications of ROS1 gene copy number gain (CNG) in non-small cell lung cancer (NSCLC) patients. We carried out fluorescent in situ hybridization with ROS1 and centromere enumeration 6 probes and immunohistochemistry for ROS1 protein expression. ROS1 rearrangement was detected in 3 of 375 samples (0.8 %); all of whom were female, never-smokers, and harbored an adenocarcinoma component. ROS1 gene CNG was found in 18 cases (4.8 %). ROS1 gene CNG was significantly associated with shorter disease-free survival (DFS, 12 vs. 58 months; p = 0.003) and shorter overall survival (OS, 40 vs. 67 months; p <0.001) than the group without CNG. Multivariate analysis confirmed that ROS1 gene CNG was significantly associated with poorer DFS (hazard ratio [HR]=2.16, 95 % confidence interval [CI] = 1.22-3.81, p = 0.008), and OS ([HR] = 2.53, 95 % [CI] = 1.31-4.89, p = 0.006). ROS1 protein overexpression was observed in 5.0 % (18 out of 357), of which 2 cases harbored ROS1 gene rearrangement. There was no statistically significant correlation between ROS1 gene CNG and protein overexpression. This study demonstrated ROS1 gene rearrangement was detected in 0.8 % of surgically resected NSCLC; and ROS1 gene CNG is an independent poor prognostic factor. This survival analyses may contribute to future studies on the utility of ROS1-targeted therapy for patients.
Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 11/2014; · 2.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The efficacy of EGFR tyrosine kinase inhibitors in EGFR mutation-positive NSCLC patients necessitates accurate, timely testing. Although EGFR mutation testing has been adopted by many laboratories in Asia, data are lacking on the proportion of NSCLC patients tested in each country, and the most commonly used testing methods.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 11/2014; · 4.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The 2004 World Health Organization classification of lung cancer contained three major forms of non-small-cell lung cancer: squamous cell carcinoma (SqCC), adenocarcinoma (AdC), and large cell carcinoma. The goal of this study was first, to assess the reproducibility of a set of histopathological features for SqCC in relation to other poorly differentiated non-small-cell lung cancers and second, to assess the value of immunohistochemistry in improving the diagnosis.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 09/2014; 9(9):1354-1362. · 4.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objectives
Although adjuvant platinum-based chemotherapy improves survival in completely resected non-small cell lung cancer (NSCLC), its effect is limited. We evaluated whether the expression of heat shock protein 70 (Hsp70) is associated with clinical outcomes in patients with completely resected NSCLC who were treated with or without adjuvant platinum-based chemotherapy.
Patients and methods
Patients who underwent curative resection for NSCLC and diagnosed as stage IIA through IIIA were included. Immunohistochemical staining for Hsp70 was performed on surgical specimens and survival rates were compared by Hsp70 expression and adjuvant platinum-based chemotherapy.
Of 327 enrolled patients, Hsp70 expression was positive in 220 (67.3%). For patients who did not receive adjuvant chemotherapy, Hsp70 expression did not significantly affect survival. However, for patients who received adjuvant chemotherapy, those with Hsp70-positive tumors had a longer disease-free survival outcome than cases with Hsp70-negative tumors (not reached vs. 27.3 months; P = 0.002), although there was no significant difference in overall survival (97.0 vs. 58.9 months, P = 0.080). In the adjuvant chemotherapy group, multivariate modeling showed that patients with Hsp70-postitive tumors had a lower risk of recurrence and death after adjusting for age, sex, performance status, pathologic stage, and histological type (disease-free survival: adjusted hazard ratio, 0.537; 95% CI, 0.362–0.796; P = 0.002; overall survival: adjusted hazard ratio, 0.663; 95% CI, 0.419–1.051; P = 0.080).
Hsp70 is a positive predictive factor in completely resected NSCLC with received platinum-based adjuvant chemotherapy.
[Show abstract][Hide abstract] ABSTRACT: FGFR1 amplification has been identified recently as an important therapeutic target in non-small-cell lung cancer (NSCLC), particularly squamous cell carcinoma (SqCC). However, data from previous studies on the clinical implications of FGFR amplification in NSCLC are inconsistent. We evaluated FGFR1 gene copy number (GCN) in 369 cases of surgically resected NSCLC using five previously reported criteria and investigated associations between clinicopathologic parameters and FGFR1 amplification. FGFR1 amplification was found in 32/369 (8.7 %) of NSCLC and was more frequent in SqCC (18.0 % in SqCC, 3.0 % in adenocarcinoma; p < 0.001) and in smokers (p < 0.001). On univariate analysis, FGFR1 amplification was significantly associated with shorter overall survival (OS, 58.6 vs 80.0 months; p = 0.033) and shorter disease-free survival (DFS, 58.5 vs 80.0 months; p = 0.042) in patients with SqCC, but this was not statistically significant on multivariate analysis (OS: hazard ratio [HR] = 1.79, 95 % confidence interval [CI] = 0.83-3.87, p = 0.139; DFS: HR = 1.73, 95 % CI = 0.93-3.21, p = 0.081). The correlation between FGFR1 amplification and protein expression was poor (rho = 0.08; p = 0.123). These results suggest that FGFR1 amplification is associated with smoking history and squamous cell carcinoma histology and might indicate poor prognosis.
Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 08/2014; · 2.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Nodular ground-glass opacities (nGGO) are a specific type of lung adenocarcinoma. ALK rearrangements and driver mutations such as EGFR and K-ras are frequently found in all types of lung adenocarcinoma. EGFR mutations play a role in the early carcinogenesis of nGGOs, but the role of ALK rearrangement remains unknown.
BMC Cancer 05/2014; 14(1):312. · 3.32 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Yes-associated protein (YAP) has been reported to be associated with the prognosis of various cancers and also to affect epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) activity in ovarian cancer cell lines. However, few studies have evaluated YAP protein expression in lung cancer, and the results have lacked consistency.
YAP expression was evaluated in a total of 205 curatively resected lung adenocarcinomas and 36 cases of EGFR-mutated TKI-treated patients. Correlations between the expression of YAP and clinicopathologic features, response to EGFR-TKI treatment, and prognostic significance were analyzed.
High cytoplasmic YAP expression was positively correlated with the clinicopathologic parameters that have been associated with favorable prognosis. Multivariate analysis revealed that high cytoplasmic YAP expression was an independent prognostic factor in lung adenocarcinomas (progression-free survival: hazard ratio [HR] 0.659; 95 % confidence interval [CI] 0.431-1.010; p = 0.050; overall survival: HR, 0.474; 95 % CI 0.263-0.854; p = 0.013) and EGFR-TKI-treated patients with EGFR mutation (progression-free survival: HR, 0.346; 95 % CI 0.146-0.818; p = 0.016; overall survival: HR, 0.291; 95 % CI 0.125-0.676; p = 0.004).
High cytoplasmic YAP expression predicted a good clinical outcome for patients with lung adenocarcinoma and in EGFR-TKI-treated patients. Therefore, YAP may play a role in EGFR-TKI-treated lung cancer, and YAP targeting may enhance therapeutic effects in combination with other cancer drugs.
Annals of Surgical Oncology 04/2014; · 3.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Previous studies have reported that pretreatment thrombocytosis is associated with poor outcomes in several cancer types. This study was designed to evaluate the prognostic significance of preoperative thrombocytosis in patients with non-small cell lung cancer (NSCLC) who undergo surgery.
We retrospectively reviewed the records of 199 patients who underwent R0 resection for NSCLC between May 2003 and July 2006 at Seoul National University Bundang Hospital, Seongnam, Korea.
The frequency of preoperative thrombocytosis was 7.5% (15/199). Patients with preoperative thrombocytosis had shorter overall survival (OS, P = 0.003) and disease-free survival (DFS, P = 0.005) than those without thrombocytosis. In multivariable analysis, patients with preoperative thrombocytosis had a significantly greater risk of death and recurrence than those without preoperative thrombocytosis (risk of death: hazard ratio (HR) 2.98, 95% confidence interval (CI) 1.39 to 6.37, P = 0.005; risk of recurrence: HR 2.47, 95% CI 1.22 to 5.01, P = 0.012). A tendency towards a shorter OS and DFS was observed in three patients with persistent thrombocytosis during the follow-up period when compared with those of patients who recovered from thrombocytosis after surgery.
Preoperative thrombocytosis was valuable for predicting the prognosis of patients with NSCLC. Special attention should be paid to patients with preoperative and postoperative thrombocytosis.
World Journal of Surgical Oncology 02/2014; 12(1):37. · 1.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Rearrangement of anaplastic lymphoma kinase (ALK) gene is the best predictor of response to crizotinib, an ALK tyrosine kinase inhibitor. However, the prevalence of the ALK fusion is low, so accurate patient identification is crucial for successful treatment using ALK inhibitors. Furthermore, most patients with lung cancer present with advanced-stage disease at the time of diagnosis, so it is important for pathologists to detect ALK-rearranged patients while effectively maximizing small biopsy or cytology specimens. In this review, we propose a guideline recommendation for ALK testing approved by the Cardiopulmonary Pathology Study Group of the Korean Society of Pathologists.
The Korean Journal of Pathology 02/2014; 48(1):1-9. · 0.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Activating mutations in the epidermal growth factor receptor (EGFR) kinase domain are correlated with dramatic clinical responses in non-small cell lung cancer patients treated with EGFR-tyrosine kinase inhibitors (TKIs). The two most common EGFR mutations, representing 85-90% of EGFR mutations, are the E746_A750 deletion in exon 19 and the L858R point mutation in exon 21. We conducted this study to evaluate the suitability of mutation-specific antibodies that can detect E746_A750 deletion and L858R mutant EGFR proteins by immunohistochemistry (IHC).
In a cohort of consecutive patients with surgically resected lung adenocarcinomas (n=240), mutant EGFR protein expression was assessed by IHC using specific antibodies (clone SP111 and SP125) to the 2 major forms of EGFR mutations. Immunoreactivity was scored as 0-3, and the results were compared with the EGFR-mutational status.
With a cutoff value of IHC 2+ for SP 111 (anti-EGFR E746_A750 del antibody) and SP 125 (anti-EGFR L858R antibody), both antibodies showed high specificity (99.0% and 89.7%, respectively) and sensitivity (70.6% and 80.4%, respectively). While cases with IHC scores of 3 using these 2 antibodies positively correlated with the EGFR-mutational status, cases with IHC scores lower than 3+ showed variable results regarding EGFR-mutational status.
Although each antibody showed relatively high specificity, some EGFR-mutant cases were not detected by the mutation-specific antibodies. Various forms of exon 19 deletions, except E746_A750, were rarely detected by the mutant-specific antibody. Therefore, IHC-negative cases require further molecular analysis to confirm the presence of EGFR mutations.
Lung cancer (Amsterdam, Netherlands) 12/2013; · 3.14 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The discovery of the chromosomal fusion product of anaplastic lymphoma kinase (ALK) with echinoderm microtubule-associated protein-like 4 (EML4) (EML4-ALK) has changed the treatment paradigm of lung cancer. In this study, we analysed the clinical characteristics, including bronchoscopic findings, of patients with EML4-ALK-positive adenocarcinoma and compared them with those of EGFR mutation-positive patients.
In this retrospective cohort study, the clinical characteristics and bronchoscopic findings of patients with ALK fusion-positive lung cancers were compared to patients with EGFR-mutant lung cancers.
Among the 440 patients with adenocarcinoma of lung screened for this study, 46 (10.4%) harboured the EML4-ALK fusion, 90 (20.4%) harboured an activating EGFR mutation, and all had adenocarcinoma. In univariate analysis, ALK-positive patients were significantly younger than EGFR-positive patients (p = 0.004) and were more commonly male (p = 0.021). An initial status of stage IV metastatic cancer was more frequently noted in EML4-ALK-positive patients (p = 0.012), with initial brain metastasis frequently observed (p = 0.007). Compared with EGFR-positive patients, EML4-ALK-positive patients were significantly more likely to have positive bronchoscopic findings, which suggested a more centralized origin (p = 0.001). EML4-ALK patients also had significantly more positive bronchoscopic findings and were more commonly male in multivariate analysis.
The EML4-ALK fusion defines a new molecular subset of NSCLC that has distinct clinical and bronchoscopic findings suggesting more proximal origin when compared to tumours harbouring EGFR mutations.
Respiratory medicine 12/2013; · 2.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Context.-Surgical removal and pathologic handling of lung tissue has a compressive effect upon its architecture. The effect of surgical atelectasis on morphology has not been examined in depth, especially with respect to lung adenocarcinomas. Objective.-To examine the influence of surgical atelectasis on morphologic lepidic growth pattern, mimicking papillary adenocarcinoma pattern. Design.-In 2 cases serial sections of resected pulmonary adenocarcinoma were used, as was a 3-dimensional reconstruction. Elastin stains were performed on primary and metastatic adenocarcinomas. Results.-Perfusion fixation of another case showed marked morphologic differences of less compressed peripheral lung tissue, emphasizing the preexisting alveolar structure. An elastic stain may help identify true lesional architecture. Conclusions.-We demonstrate that microscopic sections of adenocarcinoma in situ in compressed/collapsed tissue may give rise to a pseudopapillary pattern mimicking invasive adenocarcinoma. Accurate appreciation of different tumor architecture in lung adenocarcinoma has important biologic and clinical implications. Pathologists should be aware of the possibility of misclassification of adenocarcinoma pattern due to tissue artifacts caused by lung tissue handling.
Archives of pathology & laboratory medicine 12/2013; 137(12):1792-1797. · 2.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although IL-1beta is believed to be crucial in the pathogenesis of osteoarthritis (OA), the IL-1beta blockade brings no therapeutic benefit in human OA and results in OA aggravation in several animal models. We explored the role of a cytokine signaling 1 (SOCS1) suppressor as a regulatory modulator of IL-1beta signaling in chondrocytes.
Cartilage samples were obtained from patients with knee OA and those without OA who underwent surgery for femur neck fracture. SOCS1 expression in cartilage was assessed by immunohistochemistry. IL-1beta-induced SOCS1 expression in chondrocytes was analyzed by quantitative polymerase chain reaction and immunoblot. The effect of SOCS1 on IL-1beta signaling pathways and the synthesis of matrix metalloproteinases (MMPs) and aggrecanase-1 was investigated in SOCS1 over-expressing or knockdown chondrocytes.
SOCS1 expression was significantly increased in OA cartilage, especially in areas of severe damage (P <0.01). IL-1beta stimulated SOCS1 mRNA expression in a dose-dependent pattern (P <0.01). The IL-1beta induced production of MMP-1, MMP-3, MMP-13, and ADAMTS-4 (aggrecanase-1, a disintegrin and metalloproteinase with thrombospondin motifs 4) was affected by SOCS1 over-expression or knockdown in both SW1353 cells and primary human articular chondrocytes (all P <0.05). The inhibitory effects of SOCS1 were mediated by blocking p38, c-Jun N-terminal kinase (JNK) and nuclear factor kappaB (NF-kappaB) activation, and by downregulating transforming growth factor-beta activated kinase 1 (TAK1) expression.
Our results show that SOCS1 is induced by IL1-beta in OA chondrocytes and suppresses the IL-1beta induced synthesis of matrix degrading enzymes by inhibiting IL-1beta signaling at multiple levels. It suggests that the IL-1beta-inducible SOCS1 acts as a negative regulator of the IL-1beta response in OA cartilage.
Arthritis research & therapy 11/2013; 15(6):R191. · 4.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: MET gene copy number gain (CNG) and protein overexpression have been reported in lung cancer, but the clinical implications in early stage adenocarcinoma remain unclear.
We investigated MET gene copy number and protein expression in 141 cases of surgically resected stage I pulmonary adenocarcinoma. MET gene CNG was determined by silver in situ hybridization, and MET protein expression was assessed by immunohistochemistry. The correlation between MET gene CNG/protein expression and clinicopathologic parameters and prognostic significance was analyzed.
MET gene CNG was found in 24.1 % (34 of 141) of the cases and was associated with larger tumor size, pleural invasion, and lymphatic vessel invasion. MET gene CNG was inversely correlated with the presence of lepidic subtype (r = -0.17, p = 0.045) and was not associated with EGFR, KRAS mutation, or ALK gene rearrangement. In addition, MET gene CNG was significantly associated with shorter disease-free survival (DFS) (49 vs. 75 months; p < 0.001) and shorter overall survival (OS) (65 vs. 78 months; p = 0.01). Multivariate analysis confirmed that MET gene CNG was significantly associated with poorer DFS [p < 0.001; hazard ratio (HR) 5.5; 95 % confidence interval (CI) 2.2-13.9] but was not significantly associated with OS. MET overexpression was observed in 71.3 % of cases (97 of 136), but it was not correlated with gene CNG.
MET gene CNG is an independent poor prognostic factor in patients with stage I lung adenocarcinoma. It is associated with aggressive pathologic features and is inversely correlated with the presence of lepidic subtype.
Annals of Surgical Oncology 11/2013; · 3.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The implication of eosinophilic inflammation in chronic rhinosinusitis (CRS) has not been sufficiently studied in Asians. The aim of this study was to evaluate the relationship between eosinophilic inflammation in sinonasal tissues and the surgical outcome of functional endoscopic sinus surgery (FESS) in Koreans.
A retrospective review of medical records was performed for 347 patients who had undergone bilateral FESS. During FESS, nasal polyp (NP) or sinonasal pathological mucosa was obtained and histopathological analyses were performed. For analyses of surgical outcomes, 173 patients whose follow-up was >12 months were included. The sinonasal cavity was evaluated by endoscopic examination at the last follow-up using a Lund-Kennedy endoscopic scoring system.
Of 347 patients whose tissues were histologically evaluated, 250 (72%) had noneosinophilic CRS. The patients were categorized into four groups according to the presence of NP and eosinophilic inflammation. Of 173 patients, 43 patients (24.9%) had eosinophilic CRS with NP, 15 (8.7%) had eosinophilic CRS without NP, 74 (42.7%) had noneosinophilic CRS with NP, and 41 (23.7%) had noneosinophilic CRS without NP. There were no statistically significant differences in prevalence of allergic rhinitis and asthma and in their preoperative Lund-Mackay scores among four groups. Also, there was no statistically significant difference in the postoperative Lund-Kennedy score between eosinophilic and noneosinophilic CRS groups.
The results suggest that eosinophilic inflammation in CRS may not be related to the surgical outcome in Koreans.
American Journal of Rhinology and Allergy 11/2013; 27(6):166-9.
[Show abstract][Hide abstract] ABSTRACT: Molecular classification of lung cancer correlates well with histomorphological features. However, specific histomorphological features that differentiate anaplastic lymphoma kinase (ALK)-rearranged tumors from ALK-negative tumors have not been fully evaluated. Eighty ALK-rearranged and 213 ALK-negative (91 epidermal growth factor receptor-mutated; 29 K-ras-mutated; 93 triple-negative) resected lung adenocarcinomas were analyzed for several histomorphological parameters and histological subtype. ALK-rearranged tumors were associated with younger age at presentation, frequent nodal metastasis, and higher stage of disease at diagnosis. ALK-rearranged tumors were more likely to show a solid predominant pattern than ALK-negative tumors (43.8%; 35/80; p<0.001). Unlike ALK-negative tumors, a lepidic predominant pattern was not observed in ALK-rearranged tumors (p<0.001). In multivariate analysis, the most significant morphological features that distinguished ALK-rearranged tumors from ALK-negative tumors were cribriform formation (odds ratio [OR], 3.253; p = 0.028), presence of mucin-containing cells (OR, 4.899; p = 0.008), close relationship to adjacent bronchioles (OR, 5.361; p = 0.001), presence of psammoma bodies (OR, 4.026; p = 0.002), and a solid predominant pattern (OR, 13.685; p = 0.023). ALK-rearranged tumors exhibited invasive histomorphological features, aggressive behavior and frequent expression of epithelial-mesenchymal transition markers (loss of E-cadherin and expression of vimentin) compared with other genotype (p = 0.015). Spatial proximity between bronchus and ALK-rearranged tumors and frequent solid histologic subtype with p63 expression may cause diagnostic difficulties to differentiate squamous cell carcinoma in the small biopsy, whereas p40 was rarely expressed in ALK-rearranged adenocarcinoma. Knowledge of these features may improve the diagnostic accuracy and lead to a better understanding of the characteristic behavior of ALK-rearranged tumors.
PLoS ONE 10/2013; 8(10):e76999. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Small cell lung cancer (SCLC) transformation during epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment in lung cancer has been suggested as one of possible resistance mechanisms.
We evaluated whether SCLC transformation or neuroendocrine (NE) differentiation can be found in the cell line model. In addition, we also investigated its effect on responses to conventional chemotherapeutic drugs of the SCLC treatment.
Resistant cell lines to various kinds of EGFR-TKIs such as gefitinib, erlotinib, CL-387,785 and ZD6474 with A549, PC-9 and HCC827 lung adenocarcinoma cell lines were established. Among them, two resistant cell lines, A549/GR (resistant to gefitinib) and PC-9/ZDR (resistant to ZD6474) showed increased expressions of CD56 while increased synaptophysin, Rb, p16 and poly(ADP-ribose) polymerase were found only in A549/GR in western blotting, suggesting that NE differentiation occurred in A549/GR. A549/GR cells were more sensitive to etoposide and cisplatin, chemotherapeutic drugs for SCLC, compared to parental cells. Treatment with cAMP and IBMX induced synaptophysin and chromogranin A expression in A549 cells, which also made them more sensitive to etoposide and cisplatin than parental cells. Furthermore, we found a tissue sample from a patient which showed increased expressions of CD56 and synaptophysin after development of resistance to erlotinib.
NE differentiation can occur during acquisition of resistance to EGFR-TKI, leading to increased chemosensitivity.
Tuberculosis and Respiratory Diseases 09/2013; 75(3):95-103.