• Molecules and Cells
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• v.39 no.12
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• pp.877-887
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• 2016

Tazarotene-induced gene 1 (TIG1) is a retinoic acid-inducible protein that is considered a putative tumor suppressor. The expression of TIG1 is decreased in malignant prostate carcinoma or poorly differentiated colorectal adenocarcinoma, but TIG1 is present in benign or well-differentiated tumors. Ectopic TIG1 expression led to suppression of growth in cancer cells. However, the function of TIG1 in cell differentiation is still unknown. Using a yeast two-hybrid system, we found that transmembrane protein 192 (TMEM192) interacted with TIG1. We also found that both TIG1A and TIG1B isoforms interacted and co-localized with TMEM192 in HtTA cervical cancer cells. The expression of TIG1 induced the expression of autophagy-related proteins, including Beclin-1 and LC-3B. The silencing of TMEM192 reduced the TIG1-mediated upregulation of autophagic activity. Furthermore, silencing of either TIG1 or TMEM192 led to alleviation of the upregulation of autophagy induced by all-trans retinoic acid. Our results demonstrate that the expression of TIG1 leads to cell autophagy through TMEM192. Our study also suggests that TIG1 and TMEM192 play an important role in the all-trans retinoic acid-mediated upregulation of autophagic activity.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.6
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• pp.2385-2390
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• 2015

Background: Invasive ductal (IDC) and lobular (ILC) carcinomas are the common histological types of breast carcinoma which are difficult to distinguish when poorly differentiated. Discoidin domain receptor (DDR1) and Drosophila dishevelled protein (DVL1) were recently suggested to differentiate IDC from ILC. Objectives: To assess the expression of DDR1 and DVL1 and their association with histological type, grading and hormonal status of IDC and ILC. Materials and Methods: This cross sectional study was conducted on IDC and ILC breast tumours. Tumours were immunohistochemically stained for (DDR1) and (DVL1) as well as estrogen receptor (ER), progesterone receptor (PR) and C-erbB2 receptor. Demographic data including age and ethnicity were obtained from patient records. Results: A total of 51 cases (30 IDCs and 21 ILCs) were assessed. DDR1 and DVL1 expression was not significantly associated with histological type (p=0.57 and p=0.66 respectively). There was no association between DDR1 and DVL1 expression and tumour grade (p=0.32 and p=1.00 respectively), ER (p=0.62 and 0.50 respectively), PR (p=0.38 and p=0.63 respectively) and C-erbB2 expression (p=0.19 and p=0.33 respectively) in IDC. There was no association between DDR1 and DVL1 expression and tumour grade (p=0.52 and p=0.33 respectively), ER (p=0.06 and p=0.76 respectively), PR (p=0.61 and p=0.43 respectively) and C-erbB2 expression (p=0.58 and p=0.76 respectively) in ILC. Conclusions: This study revealed that DDR1 and DVL1 are present in both IDC and ILC regardless of the tumour differentiation. More studies are needed to assess the potential of these two proteins in distinguishing IDC from ILC in breast tumours.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3209-3212
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• 2012

Introduction: Colorectal carcinoma (CRC) is the most common gastrointestinal malignancy in the older population, but it is also quite frequent among young adults in developing countries. The aim of this study was to update the trends of clinicopathological features of CRC in young Nepalese. Methods: A retrospective comparative study on the data retrieved from the surgical records of all patients between 20 to 39 years of age with CRC was carried out for periods of 5 years each from 1999 to 2003 (early) and 2004 to 2008 (recent), treated at Tribhuvan University Teaching Hospital, Kathmandu, Nepal. Results: The number of young adults with CRC increased from 28 to 34. However, the proportion of young patients in both groups was 28% of all CRC patients. The mean ages were $34{\pm}4.7$ and $31.8{\pm}5.1$ years in early and recent 5 years, respectively, and the male female ratio changed from 2:3 to 4:3. Abdominal pain as the most common presenting symptom was replaced by bleeding per rectum in recent years. The mean duration from onset of symptoms to seeking medical advice decreased from 7.8 months to 5.6 months in recent years. More patients (85.3%) were subjected to endoscopic examination in recent years than early years (60.7%) and right colonic cancer increased from 10.7% to 26.5%. However, the rectum was the commonest site in both early (71.4%) and recent (50%) groups. CRC was detected significantly at an earlier stage (7.1% vs 32.4%) in recent years with large proportion of modified Dukes B stage. Poorly differentiated adenocarcinoma was the predominant histology in both groups (50% vs 60.7%). Curative resection had risen in recent years (39.3% vs 73.6%). Conclusion: CRC among Nepalese young adults accounts for a high incidence (28%) of all CRC cases. Although right sided colonic cancer has been increasing, rectum is the commonest site. There is also an increasing trend for diagnosis at earlier stages of the disease which can be treated with curative intent.

• Journal of Life Science
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• v.19 no.6
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• pp.705-710
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• 2009

Sodium butyrate (NaBt), a naturally occurring short chain fatty acid derived from carbohydrate metabolism in the gut, is known to exhibit strong anti-cancer potentials in various human cancer cells; however, its action mechanism is poorly understood. In the present study, we demonstrated that NaBt up-regulates levels of E-cadherin, a key cell adhesion molecule implicated as a tumor suppressor, in a cell type-specific manner. Although levels of p21, a potential activator for E-cadherin expression, were also up-regulated by treatment with NaBt in several types of cells, it does not seem to be associated with the activation of E-cadherin in the NaBt-treated cells. Instead, the data from promoter analysis suggest that NaBt up-regulates expression of E-cadherin at the transcription level by enhancing its promoter strength via a CCAAT-box. The elevated E-cadherin in the presence of NaBt was primarily localized at the cell-cell contacts, converting Hep3B cells into a more differentiated form.

• Tuberculosis and Respiratory Diseases
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• v.82 no.3
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• pp.227-233
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• 2019

Background: Programmed death-ligand 1 (PD-L1), a transmembrane protein, binds to the programmed death-1 (PD-1) receptor, and anti-PD-1 therapy enables immune responses against tumors. This study aimed to assess clinical characteristics of PD-L1 expression using immunohistochemistry among Korean patients with lung cancer. Methods: We retrospectively reviewed the data of patients with pathologically proven lung cancer from a single institution. PD-L1 expression determined by Tumor Proportion Score (TPS) was detected using 22C3 pharmDx (Agilent Technologies) and SP263 (Ventana Medical Systems) assays. Results: From July 2016 to July 2017, 267 patients were enrolled. The main histologic type was adenocarcinoma (69.3%). Most participants were smokers (67.4%) and had clinical stage IV disease (60.7%). In total, 116 (42%) and 58 (21%) patients had TPS ${\geq}1%$ and ${\geq}50%$, respectively. The patients were significantly older in TPS ${\geq}1%$ group than in TPS <1% group ($64.83{\pm}9.38years$ vs. $61.73{\pm}10.78years$, p=0.014), not in TPS ${\geq}50%$ cutoff value ($64.69{\pm}9.39$ vs. $62.36{\pm}10.51$, p=0.178). Regarding histologic grade, higher proportions of poorly differentiated tumor were observed in the TPS ${\geq}1%$ (40.8% vs. 25.8%, p=0.020) and TPS ${\geq}50%$ groups (53.2% vs. 27.2%, p=0.004). Among 34 patients examined with 22C3 and SP263 assays, 27 had positive results in both assays, with a cutoff of TPS ${\geq}1%$ (r=0.826; 95% confidence interval, 0.736-0.916). Conclusion: PD-L1 expression, defined as TPS ${\geq}1%$, was related to older age and poorly differentiated histology. There was a similar distribution of PD-L1 expression in both 22C3 and SP263 results.

• Radiation Oncology Journal
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• v.15 no.4
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• pp.369-377
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• 1997

Purpose : This study was Performed to identify the histopathologic feature by the reevaluation of the Pathologic specimen of the cervical tumors and to evaluate the clinical findings and the treatment results of the patients with small cell carcinoma of the cervix treated by radiotherapy. Materials and Methods : 2890 patients with cervical carcinoma received radiotherapy at the Department of Radiation Oncology. Yonsei Cancer Center, Yonsei University College of Medicine between October 1981 and April 1995. Of the 2890 patients in this data base, sixty were found to have small cell carcinomas $(2.08\%)$. Among them thirty six patients were transferred from other hospitals. the biopsy specimens of those Patients were not available. So we could review the slides of the other twenty four patients who were diagnosed at our hospital. Twenty four patients with small cell carcinoma of the cervix were analyzed retrospectively based on the assessment of H & E staining and other four immunohistochemical stains for neuroendocrine differentiation (neuron specific enolase, chromogranin. synaptophysin and Grimelius stain). And we also evaluate the Patients and tumor characteristics. response to radiation. patterns of failures, 5 year overall and disease free survival rates. Results : Thirteen tumors were neuroendocrine carcinomas(13/24 = $54.2\%$) and eleven tumors were squamous carcinomas, small cell type (11/24 = $47.8\%$) based on the assessment of H & E staining and other four neuroendocrine marker studies. So we classified the Patients two groups as neuroendocrine carcinoma and small cell type of squamous carcinoma, Among the 13 neuroendocrine carcinomas, five were well to moderately differentiated tumors and the other eight were Poorly differentiated or undifferentiated ones. The median age was 54 years old (range 23-79 years). Eight Patients had FIGO stage IB disease, 12 had stage 11, 3 had stage III and one had stage IV disease, Pelvic lymph node metastases were found in five Patients $(20.8\%)$. three of them were diagnosed by surgical histologic examination and the other two were diagnosed by CT scan. There was no difference between two histopathologic groups in terms of patients and tumor characteristics. response to radiation. 5 year overall and disease free survival rates. However the distant metastases rate was higher in neuroendocrine carcinoma Patients (6/13:$46.2\%$) than in small cell type of squamous carcinoma Patients (2/11:$18.2\%$), but there was no statistically significant difference because of the small number of patients (P>0.05). Conclusion : More than half of the small cell carcinoma of the cervix patients were neuroendocrine carcinoma (13/24 : $54.1\%$) by reevaluation of the biopsy specimen of the cervical tumors. The tendency of distant metastases of the neurolndocrine carcinoma was greater than those of the small cell type of squamous carcinoma $(46.2\%\;vs.\;18.2\%)$. But there were no differences in the patients and tumor characteristics and other clinical treatment results in both groups. These data suggest that radical local treatment such as radiotherapy or radical surgery combined with combination systemic cytotoxic chemotherapy might provide these patients with the best chance for cure.

• Korean Journal of Head & Neck Oncology
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• v.16 no.1
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• pp.64-68
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• 2000

Objectives: With the recent advances and increasing use of imaging techniques in examination of the neck, the incidence of incidentally discovered thyroid carcinoma has been increasing. This study was carried out to evaluate the clinicopathologic characteristics of incidental thyroid carcinomas and to find optimal therapeutic strategies for these lesions. Materials & Methods: From Jan. 1988 to Aug. 1998, 1,053 patients were operated on for thyroid cancer, of whom 127(12.1%) had incidentally discovered thyroid cancers which were identified during routine health checkups(n=40), diagnostic procedures for unrelated medical conditions(n=39) and mass screening for thyroid cancer(n=48). The preoperative diagnosis was obtained by ultrasound-guided FNAB and the extent of surgery was determined based on frozen section examinations, as well as prognostic factors and gross findings at the time of surgery. Results: There were 6 men and 121 women with a mean age of 45.9 years. Histopathological diagnosis included papillary carcinomas(n=1l9), follicular carcinomas(n=6), poorly differentiated carcinoma(n=l) and medullary carcinoma(n=1). Thirty patients(23.6%) had multifocallesions. The mean diameter of the tumors was 1.1 cm(0.2-3.4 cm). Capsular invasions were found in 53 patients(41.7%) and nodal metastases in 41(32.3%). The surgical procedures used were: 90 less-than total thyroidectomies and 37 total thyroidectomies with central neck node dissection. Lateral neck dissection was added in 5 patients. According to TNM staging, 79 patients(63.2%) were at stage I, 15(12.0%) at stage II, 31(24.8%) at stage III and 0(0.0%) at stage IV. By AMES scoring system, 102 patients(81.6%) were in the low-risk group and 23(18.4%) in the high-risk group. And by MACIS scoring system, 103(86.6%) of 119 papillary thyroid cancer patients were less than 6. Conclusions: The clinicopathological characteristics of incidentally discovered thyroid carcinomas are similar to ordinary thyroid carcinomas. The treatment of choice should be individualized based on the particular clinical situation encountered, as in ordinary thyroid carcinomas.

• Tuberculosis and Respiratory Diseases
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• v.63 no.2
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• pp.165-172
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• 2007

Background: The pathogenesis of lung cancer includes the accumulation of multiple genetic abnormalities. The CREB-binding protein(CBP) is one of several transcriptional co-activators among various sequence-specific DNA-binding transcription factors. CBP is involved in a wide range of cellular activities, such as DNA repair, cell growth, differentiation, and apoptosis that are suspected of contributing to tumorigenesis. The goal of this study was to evaluate CBP expression in a series of human lung tissues containing normal epithelium, premalignant lesions(hyperplasia and dysplasia) and squamous cell carcinomas. Materials and Methods: Immunohistochemical staining was performed on formalin-fixed paraffin-embedded sections by use of a monoclonal anti-CBP antibody. CBP expression was compared in samples from 120 patients with premalignant and malignant histological types including 20 metaplastic specimens, 40 dysplastic specimens, and 60 squamous cell carcinomas in the lung. Results: CBP expression was seen in 35% (7/20) of the metaplastic specimens. 65% (26/40) of the dysplastic specimens, and 70% (42/60) of the squamous cell carcinomas (p<0.05). According to celluar atypism, CBP expression was 50% (10/20) of the low-grade dysplastic specimens and 80% (16/20) of the high-grade dysplastic specimens(p <0.01). By cellular differentiation, CBP expression was seen in 95% (19/20) of the well differentiated squamous cell carcinomas, 85% (17/20) of the moderately differentiated carcinomas and 30% (6/20) of the poorly differentiated lesions (p <0.05). Conclusion: These results suggest that CBP may have an important role in malignant transformation of precancerous lung lesions and may be a marker for malignancy.

• Journal of Gastric Cancer
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• v.8 no.3
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• pp.136-140
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• 2008

Purpose: Stage IV early gastric carcinoma (EGC) is a rare disease. We report here on 10 cases of EGC that showed metastasis in more than 15 lymph nodes. Materials and Methods: A total of 8354 cases of gastric carcinoma in patients who underwent surgical procedures between January 2001 and January 2007 at Samsung Medical Center were studied, and 10 cases were classified as stage IV EGC. We investigated their clinicopathologic characteristics. Results: There were 5 males and 5 females. Their ages at operation ranged from 46 to 76 years with a mean age of 61. All of the 10 patients had undergone curative resection for gastric cancer. The pathological diagnosis confirmed that all of the patients had tumor confined to the submucosa. The median size of the tumors was 5.3cm and the mean number of dissected nodes was 45.5 with a mean number of 22.2 involved nodes. Six cases were classified as the diffuse type and 4 were classified as the intestinal type by Lauren's classification. Histologically, 3 cases were signet ring cell carcinoma, 3 were poorly differentiated, 2 were moderately differentiated and 2 were well differentiated adenocarcinoma. Endolymphatic invasion was found in 9 cases. The median follow-up was 31 months. Adjuvant chemotherapy was done in 9 patients, and the patient who did not receive chemotherapy died by cerebrovascular accident. 2 patient had recurrence of gastric cancer and 7 survived without recurrence. Conclusion: More cases should be collected and further studies on the molecular and cellular tumor characteristics are required to characterize these tumors that show aggressive lymphatic spread.

• Radiation Oncology Journal
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• v.6 no.1
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• pp.41-47
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• 1988

Thirty-five patients with locally advanced gastric carcinoma were treated with combined modalities of external radiation therapy (RT) and 5-FU based chemotherapy at the Division of Radiation Therapy, Department of Radiology, Kangnam 51. Mary's Hospital, Catholic University Medical College from May 1983 to May 1987. The purpose of this retrospective study is for the evaluation of the palliative response to RT. There were 25 men and 10 women. The age ranged from 38 to 80 years (median: 56 years). The pathologic classification showed $14(40\%)$ poorly differentiated, $12 (34\%)$ moderately differentiated, $3(9\%)$ well differentiated adenocarcinomas, 2 mucinous cystadenocarcinomas, 1 signet ring cell and 3 not specified ones. The time intervals from the initial surgicopathologic diagnosis to the starting day of RT was within 1 year for $18 (51\%)$, 1 to 2 years for $8 (23\%)$ and 2 to 3 years for $5 (14\%)$, respectively. The major symptoms to be treated were pain in $30 (80\%)$, mass for $29 (83\%)$, obstruction for $11 (31\%)$ and jaundice for $9 (20\%)$ patients. The response rate (patient number of positive response/total patient number) according to treated radiation doses were observed as follows; $14/16(88\%)$ for $40\~50Gy,\;8/10(80\%)$ for over $50Gy,6/8 (75\%)\;for\;30\~40Gy\;and\;8/10(53\%)\;for\;20\~30 Gy$ in decreasing order. The over ail survival was 3.0 months and that of 5FU+RT, FAM+RT and RT alone groups were 4.6 months, 3.7 months and 2.5 months respectively. Complications induced by RT were nausea and vomiting in $16(46\%)$, diarrhea in $7(20\%)$, leukopenia in $6(17\%)$ and anemia and intercurrent pneumonia in each $3(9\%)$ patients in decreasing order.