• Tuberculosis and Respiratory Diseases
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• v.57 no.4
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• pp.345-350
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• 2004

Background : To evaluate the frequency and clinical significance of lymph node micrometastasis in patients of non-small-cell lung cancer pathologically staged to be T1-2,N0. Method : From consecutive 29 patients of non-small-cell lung cancer who received curative operation and routine systemic nodal dissection, we immunohistochemically examined 806 lymph nodes from mediastinal, hilar and peribronchial lesion. All slides were stained with hematoxylin and eosin staining for one section and with cytokeratin AE1/AE3 antibody for another consecutive section of same lymph node to find out micrometastasis. Results : In 806 lymph nodes examined, no tumor cell was seen on hematoxylin and eosin staining and micrometastic foci were shown to be on 0.37%(3) of 806 lymph nodes, in which were upper paratracheal, interlobar and peribronchial lymph node. These three positive stains constitute 10.3%(3) of the 29 patients with non-small-cell lung cancer. Nine patients died from disease progression(4), postoperative complication(3) and concomitant diseases(2). The four patients with disease progression did not show evidence of micrometastasis on their lymph node examination. Conclusion : The frequency of lymph node micrometastasis was in 0.37% of 806 lymph nodes examined. The study results might suggested that routine analysis of micrometastasis on the lymph node didn't give any clinical implication on patients with non-small-cell lung cancer.

• Journal of Chest Surgery
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• v.37 no.8
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• pp.691-701
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• 2004

Background: Tissue hypoxia is a characteristic of many human malignant neoplasms, and hypoxia inducible factor-1 (HIF-1) plays a pivotal role in essential adaptive response to hypoxia, and activates a signal pathway for the expression of the hypoxia-regulated genes, resulting in increased oxygen delivery or facilitating metabolic adaptation to hypoxia. Increased level of HIF-1 a has been reported in many human malignancies, but in esophageal squamous cell carcinoma, the influence of HIF-1 a on tumor biology, including neovascularization, is not still defined. Material and Method: The influence of HIF-1 a expression on angiogenic factors, correlation between the tumor proliferation and HIF-1 a expression, interaction of HIF-1 a expression and p53, and correlation between HIF-1 a expression and clinicopathological prognostic parameters were investigated, using immunohistochemical stains for HIF-1 a, VEGF, CD34, p53, and Ki-67 on 77 cases of resected esophageal squamous cell carcinoma. Result: HIF-1 a expression in cancer cells was found in 33 of 77 esophageal squamous cell carcinoma cases. The 33 cases (42.9%) showed positive stain for HIF-1 a. High HIF-1 a expression was significantly associated with several pathological parameters, such as histologic grade (p=0.032), pathological TMN stage (p=0.002), the depth of tumor invasion (p=0.022), regional lymph node metastasis (p=0.002), distant metastasis (p=0.049), and lymphatic invasion (p=0.004). High HIF-1 a expression had significant VEGF immunoreactivity (p=0.008) and Ki-67 labeling index (p<0.001), but was not correlated with microvascular density within tumors (p=0.088). The high HIF-1 a expression was correlated with aberrant p53 accumulation with a marginal significance (p=0.056). The overall 5-year survival rate was 34.9%. The survival rate of patients with a high HIF-1 a expression was worse than that of patients with low-expression tumors (log-rank test, p=0.0001). High HIF-1 a expression was independent unfavorable factors although statistical significance is marginal in multivariate analysis. Conclusion: It is suggested that (1) high HIF-1 a expression in esophageal squamous cell carcinoma is associated with tumor hypoxia, or with genetic alteration in early carcinogenesis and progressive stages, (2) high HIF-1 a expression may be associated with intratumoral neovascularization through HIF-VEGF pathway, and (3) high HIF-1 a expression is associated with poor prognosis in patients with esophageal squamous cell carcinoma and may playa role as biomarker for regional lymph node metastasis.

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

• The Journal of the Korean Society for Microbiology
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• v.21 no.3
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• pp.311-329
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• 1986

The experimental exposure of animals to sources of ultraviolet radiation (UVR) which emit their energy primarily in the UVB region (280-320nm) is known to result in a number of well-described changes in the recipient's immune competence. Two such changes include a depressed capacity to effectively respond immunologically to transplants of syngeneic UVR tumors and a markedly reduced responsiveness to known inducers of delayedtype (DTH) and contact hypersensitivity (CH) reactions. The results of experiments that were designed to elucidate the mechanisms responsible for UVR-induced immunomodulation have implicated: 1) an altered pattern of lymphocyte recirculation, 2) suppressor T cells(Ts), 3) deviations in systemic antigen presenting cell (APC) potential. 4) changes in the production of interleukin-1-like molecules, and 5) the functional inactivation of epidermal Langerhans cells in this process. The exposure of skin to UVR, therefore, causes a number of both local and systemic alterations to the normal host immune system. In spite of this seeming complexity and diversity of responses, our recent studies have established that each of the UVR-mediated changes is probably of equal importance to creating the UVR-induced immunocompromised state. Normal animals were exposed to low dose UVR radiation on their dorsal surfaces under conditions where a $3.0\;cm^2$ area of skin was physically protected from the light energy. Contact sensitization of these animals with DNFB, to either the irradiated or protected back skin, resulted in markedly reduced CH responses. This was observed in spite of a normal responsiveness following the skin sensitization to ventral surfaces of the UVR-exposed animals. Systemic treatment of the low dose UVR recipients with the drug indomethacin (1-3 micrograms/day) during the UVR exposures resulted in a complete reversal of the depressions observed following DNFB sensitization to "protected" dorsal skin while the altered responsiveness found in the group exposed to the skin reactive chemical through directly UVR-exposed sites was maintained. These studies implicate the importance of EC as effective APC in the skin and also suggest that some of the systemic influences caused by UVR exposure involve the production of prostaglandins. This concept was further supported by finding that indomethacin treatment was also capable of totally reversing the systemic depressions in CH responsiveness caused by high dose UVR exposure (30K joules/$m^2$) of mice. Attempts to analyze the cellular mechanisms responsible established that the spleens of all animals which demonstrated altered CH responses, regardless of whether sensitization was through a normal or an irradiated skin site, contained suppressor cells. Interestingly, we also found normal levels of T effector cells in the peripheral lymph nodes of the UVR-exposed mice that were contact sensitized through normal skin. No effector cells were found when skin sensitization took place through irradiated skin sites. In spite of such an apparent paradox, insight into the probable mechanisms responsible for these observations was provided by establishing that UVR exposure of skin results in a striking and dose-dependent blockade of the efferent lymphatic vessels in all peripheral lymph nodes. Therefore, the afferent phases of immune responses can apparently take place normally in UVR exposed animals when antigen is applied to normal skin. The final effector responses, however, appear to be inhibited in the UVR-exposed animals by an apparent block of effector cell mobility. This contrasts with findings in the normal animals. Following contact sensitization, normal animals were also found to simultaneously contain both antigen specific suppressor T cells and lymph node effector cells. However, these normal animals were fully capable of mobilizing their effector cells into the systemic circulation, thereby allowing a localization of these cells to peripheral sites of antigen challenge. Our results suggest that UVR is probably not a significant inducer of suppressor T-cell activity to topically applied antigens. Rather, UVR exposure appears to modify the normal relationship which exists between effector and regulatory immune responses in vivo. It does so by either causing a direct reduction in the skin's APC function, a situation which results in an absence of effector cell generation to antigens applied to UVR-exposed skin sites, inhibiting the capacity of effector cells to gain access to skin sites of antigen challenge or by sequestering the lymphocytes with effector cell potential into the draining peripheral lymph nodes. Each of these situations result in a similar effect on the UVR-exposed host, that being a reduced capacity to elicit a CH response. We hypothesize that altered DTH responses, altered alloresponses, and altered graft-versus-host responses, all of which have been observed in UVR exposed animals, may result from similar mechanisms.

• Radiation Oncology Journal
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• v.21 no.1
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• pp.19-26
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• 2003

Purpose : Maxillary sinus cancers are usually locally advanced, and involve the structures around sinus, but the regional lymphatic spread is uncommon. Therefore, the local control of these cancers is important for their cure. We reviewed our experience of 55 patients with squamous cell carcinomas of the maxillary sinus, treated with radiation therapy, and looked for the role of radiation therapy in maxillary sinus cancers. Materials and Methods : Between November 1982 and October 1999, 55 patients with squamous cell carcinomas of the maxillary sinus underwent either radiation therapy only, or combined with surgery or with concurrent chemoradlation therapy. All patients were restaged according to the 1997 AJCC staging systems. The T classifications of the tumors of the patients were as follows 1.8$\%$ (1/55) for 72, 81.8$\%$ (45/55) for 73 and 16.4$\%$ (9/55) for 74. Thirteen patients were diagnosed with lymph node involvement. With the surgical procedures, 12 patients were managed by biopsy only, 21 were resected by FESS (funclienal endoscopic sinus surgery) and 22 by partial/medical/total rnaxillectomies. The details of the treatments were as follows 8 patients were treated with radiation therapy only, 17 with a combination of FESS and radiation therapy, 22 with a combination of a maxillectomy and radiation therapy, 4 with a combination of preoperative radiation therapy and surgery, and 4 with concurrent chemoradiation therapy. The mean follow-up for all patients was 25 months, ranging from 2.8 to 125 months. Results : The 4-year local control and survival rates for all Patients were 45.5 and 33.3$\%$, respectively. The 4-year local control and suHival rates, due to the extent of surgery, were as follows 32.1, and 21.4$\%$ for biopsy; 41.9, and 31.7$\%$ for FESS; and 56.8, and 52.7$\%$ for maxillectomy, respectively. Twenty-nine (52.7$\%$) patients were not cured, and of these 29 patients, 23 (79.3$\%$) patients had a iocal recurrence following treatment. Conclusions :This study has shown that the major failure sites following treatment to be the local regions, and that the completeness of surgery was important for improving the local control and survival of patients with squamous cell carcinoma of the maxillary sinus.

• Radiation Oncology Journal
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• v.22 no.3
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• pp.177-183
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• 2004

Purpose: Authors would report the results of sequential CHOP chemotherapy (cyclophosphamide, adriamycin, vincristine, and prednisone) and involved field radiotherapy (IFRT) for early stage nasal natural killer/T-cell Iymphoma (NKTCL). Materials and Methods: Fourteen among 17 patients, who were registered at the Samsung Medical Center tumor registry with stage I and II nasal NKTCL from March 1995 to December 1999 received this treatment protocol. Three to four cycles of CHOP chemotherapy were given at 3 weeks' interval, which was followed by local IFRT including the known tumor extent and the adjacent draining lymphatics. Results: Favorable responses after chemotherapy (before IFRT) were achievable only in seven patients (5 CR's+2 PR's: 50%), while seven patients showed disease progression. There were six patients with local failures, two with distant relapses, and none with regional lymphatic failure. The actuarial overall survival and progression-free survival at 3 years were 50.0% and 42.9%. All the failures and deaths occurred within 13 months of the treatment start. The factors that correlated with the improved survival were the absence of 'B' symptoms, the favorable response to chemotherapy and overall treatment, and the low risk by international prognostic index on univariate analyses. Conclusion: Compared with the historic treatment results by IFRT either alone or followed by chemotherapy, the current trial failed to demonstrate advantages with respect to the failure pattern and survival. Development of new treatment strategy in combining IFRT and chemotherapy is required for improving outcomes.

• Journal of Chest Surgery
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• v.25 no.3
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• pp.247-257
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• 1992

Bronchial adenoma, firstly described by Muller[1882] had been reported on the subject stressed their benign nature prior to 1940`s, but these tumors including carcinoid tumor, mucoepidermoid carcinoma, adenoid cystic carcinoma, pleomorphic adenoma are now known to possess the various degree of malignant natures from benign course, low grade malignant potential to distant lymphatic or hematogenous metastasis or combination. Although histologically diffeerent, four varieties except carcinoid tumor which is a spectrum of neu-roendocrine tumor originating Kulchitsky cell of the bronchial epithelium and form the part of the APUD tumor spectrum, are morphologically and in many respects clinically similar to the corresponding tumor of the salivary gland is a specific varient of adenocarcinoma that occurs most commonly in the major and minor salivary gland and less frequently tra-cheobronchial tree, esophagus etc. To better understand the clinical characteristics and assess more precisely the malignat nature of bronchial adenoma, we studied 17 cases of bronchial adenoma, which had been experienced at the Department of Thoracic and Cardiovascular surgery of Catholic University Medical College from April 1977 to september 1991. Seventeen cases of bronchial adenoma consist of 2 carcinoid tumors, 6 adenoid cystic carcinomas, 8 mucoepidermoid carcinomas and one pleomorphic adenoma. There is a slight predominace of male patients[10/17] and the age of pt studied varied with a higher incidence occurring between the ages of 40 years and 60 years[mean age, 46.5 years]; the youngest being 15 years and oldest 69 years. Their leading complaints were hemoptysis[4], exertional dyspnea[8], fever & chilness [4], and symptoms mimicking the bronchial asthma[4]. Diagnosis was aided by the radiologic studies such as chest X-ray, polytomography, CT scan, brochography and bronchoscopy. The preferred locations of fumor were in the trachea[4], main stem bronchus[3], bronchus intermedius[3], bronchus of RUL[2], LUL[1], RLL[1], LLL[3] with no peripheral location. Modalities of treatments were single or combination of surgical resection, radiation therapy, chemotherapy. Complete resections were permitted in 12 cases with late recurrences of 4 cases ranging from 6 months to 10 years: pneumonectomy[4], lobectomy[4], bil-obectomy[2], sleeve resection[2]. Gross findings of resected specimens in 14 cases showed that 4 cases were polyp-like pedunculated mass[entirely intraluminal mass] with intact mucosa, 8 cases were broad-bas-ed sessile mass[predominatly intraluminal] and the main portions were located below the mucosa similar to tip of iceburg[predominantly extraluminal] in 2 cases. Follow-up information was availble in all 17 cases ; eight were alive without evidence of disese ranging from 1 month to 13 years. But seven cases died of the causes related to tumor[6 cases within 12 months, one case 10 years after pneumonectomy]. We concluded that 8 cases[47%] of 17 cases were metastasizing bronchial adenoma and precise survival rate cannot be answered by the scanty materials available for study.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5199-5205
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• 2013

Background/Aim: The Hippo signaling pathway is a newly discovered and conserved signaling cascade, which regulates organ size control by governing cell proliferation and apoptosis. This study aimed to investigate its effects in human gastric cancer. Methods: Tumor tissues (n=60), adjacent non-tumor tissues (n=60) and normal tissues (n=60) were obtained from the same patients with primary gastric cancer (GC). In addition, 70 samples of chronic atrophic gastritis (CAG) tissues were obtained from patients with intestinal metaplasia (IM) by endoscopic biopsy. Hippo signaling molecules, including Mst1, Lats1, YAP1, TAZ, TEAD1, Oct4 and CDX2, were determined by quantitative polymerase chain reaction (qPCR). Protein expression of Mst1, Lats1, YAP1, TEAD1 and CDX2 was assessed by immunohistochemistry and Western blotting. Results: Mst1, Lats1 and Oct4 mRNA expression showed an increasing tendency from GC tissues to normal gastric tissues, while the mRNA expression of YAP1, TAZ and TEAD1 was up-regulated (all P<0.01). Mst1 and Lats1 protein expression presented a similar trend with their mRNA expression. In addition, YAP1 and TEAD1 protein expression in GC was significantly higher than in the other groups (all P<0.01). CDX2 mRNA and protein expression in the CAG group were higher than in the other groups (all P<0.01). In GC, mRNA expression of Mst1, Lats1, Oct4, YAP1, TAZ, TEAD1 and CDX2 had a close correlation with lymphatic metastasis and tumor TNM stage (all P<0.01). Furthermore, protein expression of Mst1, Lats1, YAP1, TAZ, TEAD1 and CDX2 had a close correlation between each other (P<0.05). Conclusion: The Hippo signaling pathway is involved in the development, progression and metastasis of human gastric cancer. Therefore, manipulation of Hippo signaling molecules may be a potential therapeutic strategy for gastric cancer.

• Journal of Gastric Cancer
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• v.7 no.3
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• pp.160-166
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• 2007

Purpose: Recently, chemosensitivity tests have become widely used for the selection of effective drugs in gastric cancer patients. In this study, a chemosensitivity test was performed to select agents to increase the effectiveness of adjuvant chemotherapy. Materials and Methods: Chemosensitivity testing was performed in 81 gastric cancer patients that received a gastrectomy at the Yeungnam University Hospital. An ATP (adenosine triphosphate) based chemotherapy response assay was used. Clinicopatholgical factors such as sex, age, expression of tumor markers (CEA and CA19-9 levels), location of the tumor, morphology of advanced cancer, histological type, cell differentiation, depth of invasion, Lauren classification, Ming classification, lymphatic invasion, vascular invasion, neural invasion, lymph node metastasis and TNM stage were used to correlate the chemosensitivity and clinicopathological factors. Results: The most effective antitumor agents in gastric cancer patients were (in order of effectiveness) 5-FU, Epirubicin, lrinotecan and Oxaliplatin in our series. The chemosensitivity test showed a significant difference in susceptibility according to clinicopathological factors. Conclusion: Further studies on multidrug therapy are needed to evaluate synergistic effects of drugs. Therefore, for effective chemotherapy, it is more efficacious to select a chemosensitive drug than continue to use the same drug regimen.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.32 no.4
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• pp.420-426
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• 1999

We examined the immune response in flounder, Paralichthys olivaceus, with immunization of formalin killed Edwardsiella tarda as an antigen. The ELISPOT-assay (enzyme-linked immunospot assay) was optimized technically and applied to count the number of total and specific antibody secreting cells (TASC and SASC) in lymphocytes of different lymphatic organs. Incubation of lymphocytes on 96 well plate for more than 2.5hrs came out enough time in ELISPOT-assay for counting the antibody secreting cells in the anterior kidney and spleen. However, too much of plate-coated antigen or rabbit anti-flounder immunoglobulin for SASC or TASC counting, respectively, was appeared to decrease the sensitivity of the assay system. Specificity of the system was also confirmed by the absence of TASC in lymphocytes treated with cycloheximide to prevent protein synthesis. The peak numbers of SASC appeared at wk 3 post immunization after that there was a sharp decrease and reached to almost zero at wk 7. In the spleen and kidney, the timing and numbers of SASC on peak response were concurrent without preferential organ distribution. The specific antibody level in the sera increased rapidly between wk 2 and 3 after immunization, i.e. like the specific cellular response found with ELISPOT-assay on that period, However, the remained high level of specific serum antibody from wk 5 after immunization until the end of experiment was clearly distinguishable from the kinetics of SASC response decreased sharply.