• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.7
• /
• pp.4279-4282
• /
• 2013

Background: The activation and inactivation of receptor tyrosine kinases are tightly regulated to ensure faithful replication of cells. After having transduced extracellular growth activating signals, activated EGFR is subjected to downregulation either by clathrin mediated endocytosis or c-Cbl mediated proteasome degradation depending on the ligand concentration. c-Cbl is an ubiquitin ligase which requires a phosphorylated tyrosine residue at position 1045 in the cytoplasmic domain of EGFR to interact and add ubiquitin molecules. While activating mutations in exons 19 and 21 have been associated with the development of several cancers, the status of mutations at tyrosine 1045 coding exon 27 of EGFR remain to be investigated. Consistently, defective phosphorylation at 1045 has been associated with sustained phosphorylation of EGFR in non-small lung carcinomas. Hence in the present study we investigated the genetic status of the tyrosine 1045 coding site within exon 27 of EGFR gene to explore for possible occurrence of mutations in this region, especially since no studies have addressed this issue so far. Materials and Methods: Tumor chromosomal DNA isolated from thirty five surgically excised oral squamous cell carcinoma tissues was subjected to PCR amplification with intronic primers flanking the tyrosine 1045 coding exon 27 of EGFR gene. The PCR amplicons were subsequently subjected to direct sequencing to elucidate the mutation status. Results: Sequence analysis identified no mutations in the tyrosine 1045 codon of EGFR in any of the thirty five samples that were analyzed. Conclusions: The lack of identification of mutation in the tyrosine 1045 codon of EGFR suggests that mutations in this region may be relatively rare in oral squamous cell carcinomas. To the best of our knowledge, this study is the first to have explored the genetic status of exon 27 of EGFR in oral squamous cell carcinoma tissue samples.

• Journal of Microbiology and Biotechnology
• /
• v.31 no.2
• /
• pp.197-206
• /
• 2021

microRNA-361-3p (miR-361-3p) is involved in the carcinogenesis of oral cancer and pancreatic catheter adenocarcinoma, and has anti-carcinogenic effects on non-small cell lung cancer (NSCLC). However, its effect on multiple myeloma (MM) is less reported. Here, we found that upregulating the expression of miR-361-3p inhibited MM cell viability and promoted MM apoptosis. We measured expressions of tumor necrosis factor receptor-associated factor 6 (TRAF6) and miR-361-3p in MM cells and detected the viability, colony formation rate, and apoptosis of MM cells. In addition, we measured expressions of apoptosis-related genes Bcl-2, Bax, and Cleaved caspase-3 (C caspase-3). The binding site between miR-361-3p and TRAF6 was predicted by TargetScan. Our results showed that miR-361-3p was low expressed in the plasma of MM patients and cell lines, while its overexpression inhibited viability and colony formation of MM cells and increased the cell apoptosis. Furthermore, TRAF6, which was predicted to be a target gene of miR-361-3p, was high-expressed in the plasma of patients and cell lines with MM. Rescue experiments demonstrated that the effect of TRAF6 on MM cells was opposite to that of miR-361-3p. Upregulation of miR-361-3p induced apoptosis and inhibited the proliferation of MM cells through targeting TRAF6, suggesting that miR-361-3p might be a potential target for MM therapy.

• Tuberculosis and Respiratory Diseases
• /
• v.58 no.1
• /
• pp.54-58
• /
• 2005

Background : To evaluate the role of estrogen and progesterone in the carcinogenesis of NSCLC, IHC studies for the expression of the receptors of estrogen and progesterone have been performed with inconsistent results. Recently the TMA method has been developed and has become recognized as a useful and rapid method for extensively analysing molecular markers at the gene and protein level. We have investigated their expressions in the tissue from NSCLC using the microarray method. Methods : The TMA construction was made with 70 formalinfixed, paraffin-embedded tissues of NSCLC. After heat-induced epitope retrieval, IHC staining on primary tissues of NSCLC was performed with the monoclonal antibodies, ER1D5 and PR1A6. Results : Our sample of 70 consisted of 74% men and 26% women. Of the patients, 49% were current smokers, 27% were non-smokers and 24% were former smokers. By histologic classification, 34 patients had squamous cell carcinoma, 24 had adenocarcinoma, 9 had adenosquamous cell carcinoma, and 3 had other carcinomas. No cancer cells were immunostained with these monoclonal antibodies in any primary tissues of NSCLC. Conclusions : No expression of neither of the two receptors was found in any of the lung cancer tissues. This suggests that adequate genetic variants for IHC staining need to be developed for NSCLC.

• Journal of Chest Surgery
• /
• v.55 no.1
• /
• pp.10-19
• /
• 2022

Background: According to the eighth TNM (tumor-node-metastasis) staging system, the presence of separate tumor nodules in the same lobe is designated as a T3 descriptor. However, it remains unclear whether adjuvant chemotherapy confers survival advantages in this setting. Methods: We retrospectively identified 142 pathologic T3N0M0 patients with additional pulmonary nodules in the same lobe from a single-institutional database from 2004 to 2019. The main outcomes were overall survival and recurrence-free survival. Multivariable Cox regression was used to identify the benefit of adjuvant chemotherapy while adjusting for other variables. Results: Sixty-one patients received adjuvant chemotherapy (adjuvant group) and 81 patients did not receive adjuvant therapy after surgery (surgery-only group). There were no demonstrable differences between the 2 groups regarding hospital mortality and postoperative complications, indicating that treatment selection had not significantly occurred. However, the use of adjuvant chemotherapy was associated with improved 5-year overall survival (70% vs. 59%, p=0.006) and disease-free survival (60% vs. 46%, p=0.040). A multivariable Cox model demonstrated that adjuvant chemotherapy was associated with a survival advantage (adjusted hazard ratio, 0.54; p<0.001). In exploratory analyses of subgroups, the effect of adjuvant chemotherapy seemed to be insufficient in those with small main tumors (<4 cm). Conclusion: Adjuvant chemotherapy was associated with better survival in T3 cancers with an additional tumor nodule in the same lobe. However, the role of adjuvant chemotherapy in patient subgroups with small tumors or those without risk factors should be determined via large studies.

• Radiation Oncology Journal
• /
• v.21 no.4
• /
• pp.253-260
• /
• 2003

Purpose: No general consensus has been reached regarding the necessity of postoperative radiation therapy (PORT) and the optimal techniques of its application for patients with chest wall invasion (pT3cw) and node negative (NO) non-small cell lung cancer (NSCLC). We retrospectively analyzed the PT3cwN0 NSCLC patients who received PORT because of presumed inadequate resection margin on surgical findings. Materials and Methods: From Aug. 1994 till June 2000, 21 pT3cwN0 NSCLC patients received PORT at Samsung Medical Center; all of whom underwent curative on-bloc resection of the primary tumor plus the chest wall and regional lymph node dissection. PORT was typically stalled 3 to 4 weeks after operation using 6 or 10 MV X-rays from a linear accelerator. The radiation target volume was confined to the tumor bed plus the immediate adjacent tissue, and no regional lymphatics were included. The planned radiation dose was 54 Gy by conventional fractionation schedule. The survival rates were calculated and the failure patterns analyzed. Results: Overall survival, disease-free survival, loco-regional recurrence-free survival, and distant metastases-free survival rates at 5 years were 38.8$\%$, 45.5$\%$, 90.2$\%$, and 48.1$\%$, respectively. Eleven patients experienced treatment failure: six with distant metastases, three with intra-thoracic failures, and two with combined distant and intra-thoracic failures. Among the five patients with intra-thoracic failures, two had pleural seeding, two had in-field local failures, and only one had regional lymphatic failure in the mediastinum. No patients suffered from acute and late radiation side effects of RTOG grade 3 or higher. Conclusion: The strategy of adding PORT to surgery to improve the probability, not only of local control but also of survival, was justified, considering that local control was the most important component in the successful treatment of pT3cw NSCLC patients, especially when the resection margin was not adequate. The incidence and the severity of the acute and late side effects of PORT were markedly reduced, which contributed to improving the patients' qualify of life both during and after PORT, without increasing the risk of regional failures by eliminating the regional lymphatics from the radiation target volume.

• Tuberculosis and Respiratory Diseases
• /
• v.47 no.5
• /
• pp.642-649
• /
• 1999

Background: It is very important to determine an accurate staging of the non-small cell lung cancer(NSCLC) for an assessment of operability and it's prognosis. However, it is difficult to evaluate tumor involvement of mediastinal lymph nodes accurately utilizing noninvasive imaging modalities. PET is one of the sensitive and specific imaging modality. Unfortunately PET is limited use because of prohibitive cost involved with it's operation. Recently hybrid SPECT/PET(single photon emission computed tomography/positron emission tomography) camera based PET imaging was introduced with relatively low cost. We evaluated the usefulness of coincidence detection(CoDe) PET in the detection of metastasis to the mediastinal lymph nodes in patients with NSCLC. Methods: Twenty one patients with NSCLC were evaluated by CT or MRI and they were considered operable. CoDe PET was performed in all 21 patients prior to surgery. Tomographic slices of axial, coronal and sagittal planes were visually analysed. At surgery, mediastinal lymph nodes were removed and histological diagnosis was performed. CoDe PET findings were correlated with histological findings. Results: Twenty of 21 primary tumor masses were detected by the CoDe PET. Thirteen of 21 patients was correctly diagnosed mediastinal lymph node metastasis by the CoDe PET. Pathological N0 was 14 cases and the specificity of N0 of CoDe PET was 64.3%. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of N1 node was 83.3%, 73.3%, 55.6%, 91.7%, and 76.2% respectively. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of N2 node was 60.0%, 87.5%, 60.0%,87.5%, and 90.0% respectively. There were 3 false negative cases but the size of the 3 nodes were less than 1cm. The size of true positive nodes were 1.1cm, 1.0cm, 0.5cm respectively. There were 1 false positive among the 12 lymph nodes which were larger than 1cm. False positive cases consisted of 1 tuberculosis case, 1 pneumoconiosis case and 1 anthracosis case. Conclusion: CoDe PET has relatively high negative predictive value in the enlarged lymph node in staging of mediastinal nodes in patients with NSCLC. Therefore CoDe PET is useful in ruling out metastasis of enlarged N3 nodes. However, further study is needed including more number of patients in the future.

• Radiation Oncology Journal
• /
• v.16 no.3
• /
• pp.275-282
• /
• 1998

Purpose : The effect of hyperfractionated radiotherapy on locally advanced non-small lung cancer was studied by a retrospective analysis. Materials & Methods : We analyzed sixty one patients of biopsy-confirmed, IIIA and IIIB non-small cell lung cancer. Using the ECOG performance scale, all the patients were scored less than 2. They were treated by curative hyperfractionated radiotherapy alone from Oct. 1992 to Oct. 1995 at the Department of Radiation Oncology. All the patients received 120cGy b.i.d with more than 6 hours interval between each fraction. The total dose of radiation was reached up to 6400-7080 cGy with a mean dose of 6934 cGy. The results were analyzed retrospectively. Results : The overall survival rate was 53 1$\%$ in 1 year, 9.9$\%$ in 2 years with a median survival time (MST) of 13.9 months. The progression free survival (PFS) rate was 37.0$\%$ in 1 year, 8.9$\%$ in 2 years. Twenty two Patients were classified as complete responders to this treatment and their MST was 19.5 months When this was compared with that of partial responders (MST: 11 7months), it was statistically significant (p=0.0003). Twenty nine patients of stage IIIA showed a better overall survival rate (1yr 63.3$\%$, 2yr 16.8$\%$) than IIIB patients (1yr 43.3$\%$, 2yr 3.6$\%$), which was also statistically significant (p=0.003). Patients with adenocarcinoma showed a better survival rate (1yr 64.3$\%$, 2yr 21.4$\%$) than that of squamous cell counterpart (1yr 49.4$\%$, 2yr 7.4$\%$), although this was not significant statistically (p=0.61). Two patients developed fatal radiation-induced pneumonia right after the completion of the treatment which progressed rapidly and they all died within 2 months. One patient developed radiation-induced fibrosis after 13 months. He refused further treatment and died soon after the development of fibrosis. Conclusion : Among locally advanced NSCLC, hyperfractionated radiotherapy was effective on stage IIIA patients by increasing MST with acceptable toxicities. Acute radiation-induced pneumonia should be carefully monitored and must be avoided during or after this treatment.

• Tuberculosis and Respiratory Diseases
• /
• v.48 no.4
• /
• pp.428-437
• /
• 2000

Background : Five year survival rate of postoperative stage I non-small cell lung cancer(NSCLC) reaches to 66%. In the remaining one third of patients, however, cancer recurs and the overall survival of NSCLC remains dismal. To evaluate clinical and pathologic characteristics of recurred NSCLC, the patterns and factors for postoperative recurrence in patients with staged I and II NSCLC were studied. Method : A retrospective analysis was performed in 234 patients who underwent radical resection for pathologic stage I and II NSCLC. All patients who were followed up for at least one year were included in this study. Results : 1) There were 177 men and 57 women The median age was 63. The median duration of the follow up period was 732 days (range 365~1,695 days). The overall recurrence rate was 26.5%, and the recurrence occurred $358.8{\pm}239.8$ days after operation. 2) The ages of recurred NSCLC patients were higher ($63.2{\pm}8.8$ years) than those of non-recurred patients ($60.3{\pm}9.8$ years)(p=0.043). The recurrence rate was higher in stage II (46.9%) than in stage I (18.8%) NSCLC p<0.001. The size of primary lung mass was larger in recurred ($5.45{\pm}3.22\;cm$) than that of non-recurred NSCLC ($3.74{\pm}1.75\;cm$, p<0.001). Interestingly, there were no recurrent cases when the resected primary tumor was less than 2cm. 3) Distant recurrence was more frequent than locoregional recurrence (66.1% vs. 33.9%). Distant recurrence rate was higher in females and in cases of adenocarcinoma. Brain metastasis was more frequent in patients with adenocarcinoma than in those with squamous cell carcinoma (p=0.024). Conclusion: The tumor size and stage were two important factors for determining the possibility of a recurrence. Because distant brain metastasis was more frequent in patients with adenocarinoma, a prospective study should be conducted to evaluate the effectiveness of preoperative brain imaging.

• Tuberculosis and Respiratory Diseases
• /
• v.76 no.3
• /
• pp.114-119
• /
• 2014

Background: Epigallocatechin-3-gallate (EGCG), a major biologically active component of green tea, has anti-cancer activity in human and animal models. We investigated the schedule-dependent effect of EGCG and paclitaxel on growth of NCI-H460 non-small cell lung cancer cells. Methods: To investigate the combined effect of EGCG (E) and paclitaxel (P), combination indices (CIs) were calculated, and cell cycle analysis was performed. For the effect on cell apoptosis, western blot analysis was also performed. Results: CI analysis demonstrated that both concurrent and sequential E ${\rightarrow}$ P treatments had antagonistic effects (CIs >1.0), but sequential P ${\rightarrow}$ E had synergistic effects (CIs <1.0), on the growth inhibition of NCI-H460 cells. In the cell cycle analysis, although paclitaxel induced $G_2/M$ cell cycle arrest and increased the sub-G1 fraction, concurrent EGCG and paclitaxel treatments did not have any additive or synergistic effects compared with the paclitaxel treatment alone. However, western blot analysis demonstrated that sequential P ${\rightarrow}$ E treatment decreased the expression of Bcl-2 and procaspase-3 and increased poly(ADP-ribose) polymerase (PARP) cleavage; while minimal effects were seen with concurrent or sequential E ${\rightarrow}$ P treatments. Conclusion: Concurrent or sequential E ${\rightarrow}$ P treatment had opposite effects to P ${\rightarrow}$ E treatment, where P ${\rightarrow}$ E treatment showed a synergistic effect on growth inhibition of NCI-H460 cells by inducing apoptosis. Thus, the efficacy of EGCG and paclitaxel combination treatment seems to be schedule-dependent.

• Journal of Chest Surgery
• /
• v.43 no.6
• /
• pp.681-686
• /
• 2010

Background: A chest computed-tomography has become more prevalent so that it is more common to detect small sized pulmonary nodules that have not been found in previous simple chest x-ray. If those detected nodules are undersized or located in pulmonary parenchyma, it is difficult to accomplish a biopsy since it is vulnerable to explore them either grossly or digitally. Thus, in our hospital, a thoracoscopic pulmonary wedge resection was performed after locating a lesion by means of hook wire with CT-guided. Material and Method: 31 patients (17 males and 14 female patients) from December in 2006 to June in 2010 became our subjects; their 34 pulmonary nodules were subjected to the thoracoscopic pulmonary wedge resection after locating a lesion by means of hook wire with CT-guided. Also we analyzed a possibility of hook wire dislocation, a frequency of conversion to open thoracotomy, time consumed to operation after location of a lesion, operation time, post operation complication, and histological diagnosis of the lesion. Result: 12 of 34 cases were ground glass lesion, whereas 22 cases of them were solitary pulmonary lesion. The median value of the lesion was 8mm in size (range: 3 to 23 mm), while the median value was 12.5 mm in depth (range: 1 to 34 mm). The median value of time consumed from location of the lesion to anesthetic induction was 86.5 minutes (41~473 minutes); furthermore the mean value of operation time was 103 minutes (25~345 minutes). Intrathoracic wire dislocation was found in one case, but a target lesion was successfully excised. Open thoracotomy was performed in four cases due to pleural adhesion. However, there was no case of conversion to open thoracotomy due to failure to detect a target lesion. In histological diagnosis, metastatic cancer were found in 15 cases, which were the most common, primary lung cancer were in 9 cases, non-specific inflammation were in 3 cases, tuberculosis inflammation were in 2 cases, lymph nodes were in 2 cases, active tuberculosis were in 1 case, atypical adenomatous hyperplasia was in 1 case and normal lung parenchymal finding was in 1 case, respectively. Conclusion: In our hospital, in order to accomplish a precise histological diagnosis of ground-glass lesion and pulmonary nodules in lung parenchyma, location of pulmonary nodules were exactly located with hook wire under chest computed-tomography, which was followed by lung biopsy. We concluded that this was an accurate, minimally invasive and valuable method to minimize the complications and increase of cost of medical service provided.