[Show abstract][Hide abstract] ABSTRACT: Metformin is the most widely used anti-diabetic drug in the world. Recent evidence indicates that metformin could potentially inhibit tumorigenesis. In the present study, we found that metformin inhibited cell migration and invasion of phorbol 12-myristate 13-acetate-induced MCF-7 and tamoxifen-resistant MCF-7 breast cancer cells. This inhibition was correlated with the modulation of matrix metalloproteinase-9 (MMP9) via the suppression of its expression and proteolytic activity. These results indicate that metformin leads to the suppression of migration and invasion through regulation of MMP9 and it may have potential as an anticancer drug for therapy in human breast cancer, especially of chemoresistant cancer cells.
Anticancer research 08/2014; 34(8):4127-34. · 1.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: An increased understanding of the genetic pathways involved in renal cell carcinoma has resulted in the development of various drugs that target relevant signaling cascades for the specific treatment of this disease. However, no validated predictive markers have been identified to guide the decision whether patients should receive vascular endothelial growth factor-targeted therapy or mammalian target of rapamycin-targeted therapy. We present what is, to the best of our knowledge, the first case of renal cell carcinoma in a patient with tuberous sclerosis complex who was successfully treated with everolimus.
The patient was a 49-year-old Korean woman with tuberous sclerosis complex and recurrent renal cell carcinoma. The patient was treated with the tyrosine kinase inhibitor sunitinib followed by the mammalian target of rapamycin inhibitor everolimus. This treatment resulted in a prolonged response and significant clinical benefit. Notably, everolimus ameliorated the symptoms related not only to renal cell carcinoma but also to tuberous sclerosis complex.
This case provides a rationale for the use of everolimus as first-line treatment for this specific patient population in order to target the correct pathway involved in carcinogenesis.
[Show abstract][Hide abstract] ABSTRACT: Vascular endothelial growth factor (VEGF) seems to be involved in the pathogenesis of chronic obstructive pulmonary disease (COPD), but its site-specific expression in lung tissue and the relationship with hypoxia inducible factor-1 alpha (HIF-1α) expression in chronic bronchitis (CB) type COPD have not been studied.
We evaluated the expression of VEGF and its receptors in various compartments of lung tissue in three groups: non-smokers with normal lung function (non-smokers, n=10), smokers without COPD (healthy smokers, n=10) and smokers with CB (CB, n=10), using immunohistochemical staining and Western blotting. The expression of HIF-1α was assessed by enzyme-linked immunosorbent assay.
Compared with healthy smokers, VEGF expression in CB was significantly increased in bronchiolar epithelium, vascular endothelium and vascular smooth muscle (p<0.05). VEGF receptor (VEGFR)-2 expression in CB was also increased in bronchiolar smooth muscle, vascular endothelium and vascular smooth muscle compared with healthy smokers (p<0.05). The level of HIF-1α was increased in CB compared with healthy smokers and positively correlated with those of VEGF (r=0.64, p<0.05).
VEGF and VEGFR-2 expression was up-regulated in CB and increased expression of VEGF was related with HIF-1α. HIF-1α-regulated VEGF overexpression may be a characteristic of chronic bronchitis.
[Show abstract][Hide abstract] ABSTRACT: Naked cuticle Drosophila 1 (NKD1) has been related to non-small cell lung cancer in that decreased NKD1 levels have been associated with both poor prognosis and increased invasive quality.
Forty cases of lung adenocarcinoma staged as Tis or T1a were selected. Cases were subclassified into adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and small adenocarcinoma (SAD). Immunohistochemical studies for NKD1 were performed.
Forty samples comprised five cases of AIS (12.5%), eight of MIA (20.0%), and 27 of SAD (67.5%). AIS and MIA showed no lymph node metastasis and 100% disease-free survival, whereas among 27 patients with SAD, 2 (7.4%) had lymph node metastasis, and 3 (11.1%) died from the disease. Among the 40 cases, NKD1-reduced expression was detected in 8 (20%) samples, whereas normal expression was found in 15 (37.5%) and overexpression in 17 (42.5%). Loss of NKD1 expression was significantly associated with lymph node metastasis (p=0.001). All cases with predominant papillary pattern showed overexpression of NKD1 (p=0.026).
Among MIA and SAD, MIA had better outcomes than SAD. Down-regulated NKD1 expression was closely associated with nodal metastasis, and overexpression was associated with papillary predominant adenocarcinoma.
The Korean Journal of Pathology 06/2013; 47(3):211-8. · 0.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Myxoid liposarcoma is a subtype of liposarcoma. This specific subtype can be identified based on its characteristic histological and cytogenetical features. The tumor has a fusion transcript of the CHOP and TLS genes, which is caused by t(12;16)(q13;p11). Most of the fusion transcripts that have been identified fall into three categories, specifically type I (exons 7-2), type II (exons 5-2), and type III (exons 8-2). A total of seven myxoid liposarcomas associated with the rare phenomenon of cartilaginous differentiation have been documented in the literature. Currently, only one of these cases has been cytogenetically analyzed, and the analysis indicated that it was a type II TLS-CHOP fusion transcript in both the typical myxoid liposarcoma and cartilaginous areas. This study presents a second report of myxoid liposarcoma with cartilaginous differentiation, and includes a cytogenetical analysis of both the myxoid and cartilaginous areas.
The Korean Journal of Pathology 06/2013; 47(3):284-8. · 0.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The epidermal growth factor receptor (EGFR) is a surrogate marker for basal-like breast cancer. A recent study suggested that EGFR may be used as a target for breast cancer treatment.
A total of 706 invasive ductal carcinomas (IDC) of the breast were immunophenotyped, and 82 cases with EGFR protein expression were studied for EGFR gene amplification.
EGFR protein was expressed in 121 of 706 IDCs (17.1%); 5.9% were of luminal type, 25.3% of epidermal growth factor receptor 2 (HER-2) type, and 79.3% of basal-like tumors. EGFR gene amplification and high polysomy (fluorescent in situ hybridization [FISH]-positive) were found in 18 of 82 cases (22.0%); 41.2% of the HER-2(+), EGFR(+), cytokeratin 5/6(-) (CK5/6(-)) group, 11.2% of the HER-2(-), EGFR(+), CK5/6(-) group, and 19.1% of the HER-2(-), EGFR(+), CK5/6(+) group. FISH-positive cases were detected in 8.3% of the EGFR protein 1(+) expression cases, 15.9% of 2(+) expression cases, and 38.5% of 3(+) expression cases. In group 2, the tumors had a high Ki-67 labeling (>60%), but the patients showed better disease-free survival than those with tumors that co-expressed HER-2 or CK5/6.
EGFR-directed therapy can be considered in breast cancer patients with EGFR protein overexpression and gene amplification, and its therapeutic implication should be determined in HER-2 type breast cancer patients.
The Korean Journal of Pathology 04/2013; 47(2):107-15. · 0.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Increased expression of thymidylate synthase (TS) is thought to be associated with resistance to antifolate drugs such as pemetrexed. Excision repair cross-complementation group 1 (ERCC1) is a predictive marker for platinum-based chemotherapy. This study evaluated whether the expression of TS and ERCC1 proteins is associated with clinical outcomes of the patients with pulmonary adenocarcinoma who were treated with pemetrexed/cisplatin as first-line chemotherapy. The expressions of TS and ERCC1 were evaluated by immunohistochemistry in biopsy specimens obtained from patients with pulmonary adenocarcinoma who had received pemetrexed/cisplatin as first-line treatment. Patients were categorized according to median H-score. Response rate (RR), progression-free survival (PFS) and overall survival (OS) were analyzed retrospectively. Both low TS and ERCC1 expressions were significantly associated with better RR (p=0.037 and p=0.015, respectively) and longer PFS (p<0.001 and p=0.004, respectively). Low ERCC1 expression was also associated with longer OS (p=0.003) while TS only showed a trend (p=0.105). TS expression was independent predictor for the better PFS in multivariate analysis (hazard ratio [HR]=0.32, 95% confidence interval [CI]: 0.14-0.76). Combining the two markers, the low TS/low ERCC1 group showed significantly longer PFS (HR=0.48, 95% CI: 0.26-0.75) and OS (HR=0.57, 95% CI: 0.36-0.89) compared with high TS/high ERCC1 group. Protein expressions of TS and ERCC1 were associated with clinical outcomes in patients with pulmonary adenocarcinoma who were treated with pemetrexed/cisplatin as first-line chemotherapy. TS and ERCC1 protein expressions can be potential predictive markers in this setting.
Lung cancer (Amsterdam, Netherlands) 03/2013; · 3.14 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigated the incidence of diversion colitis (DC) and impact of DC symptoms on quality of life (QoL) after ileostomy reversal in rectal cancer.
We performed a prospective study with 30 patients who underwent low anterior resection and the creation of a temporary ileostomy for the rectal cancer between January 2008 and July 2009 at the Department of Surgery, Korea University Anam Hospital. The participants totally underwent two rounds of the examinations. At first examination, endoscopies, tissue biopsies, and questionnaire survey about the symptom were performed 3-4 mo after the ileostomy creations. At second examination, endoscopies, tissue biopsies, and questionnaire survey about the symptom and QoL were performed 5-6 mo after the ileostomy reversals. Clinicopathological data were based on the histopathological reports and clinical records of the patients.
At the first examination, all of the patients presented with inflammation, which was mild in 15 (50%) patients, moderate in 11 (36.7%) and severe in 4 (13.3%) by endoscopy and mild in 14 (46.7%) and moderate in 16 (53.3%) by histology. At the second examination, only 11 (36.7%) and 17 (56.7%) patients had mild inflammation by endoscopy and histology, respectively. There was no significant difference in DC grade between the endoscopic and the histological findings at first or second examination. The symptoms detected on the first and second questionnaires were mucous discharge in 12 (40%) and 5 (17%) patients, bloody discharge in 5 (17%) and 3 (10%) patients, abdominal pain in 4 (13%) and 2 (7%) patients and tenesmus in 9 (30%) and 5 (17%) patients, respectively. We found no correlation between the endoscopic or histological findings and the symptoms such as mucous discharge, bleeding, abdominal pain and tenesmus in both time points. Diarrhea was detected in 9 patients at the second examination; this number correlated with the severity of DC (0%, 0%, 66.7%, 33.3% vs 0%, 71.4%, 23.8%, 4.8%, P = 0.001) and the symptom-related QoL (r = -0.791, P < 0.001).
The severity of DC is related to diarrhea after an ileostomy reversal and may adversely affect QoL.
World Journal of Gastroenterology 01/2013; 19(4):542-9. · 2.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: MicroRNAs (miRs) are small noncoding RNAs that have been reported to be promising diagnostic tools. We used quantitative real-time reverse transcription PCR (RT-qPCR) to analyze differentially expressed miRNAs in prostate tumor samples to determine its prognostic value. From 2007 to 2009, tumor tissues were obtained from 73 radical prostatectomy specimens. Differentially expressed miR-96, -145 and -221 were validated by TaqMan RT-qPCR using all 73 tissues. The prognostic value was assessed in terms of biochemical recurrence using Kaplan-Meier and Cox regression analyses. For our patient cohort, the mean age was 64.7 years (50-76 years) and the mean prostate-specific antigen (PSA) was 7.5 ng ml(-1). During the follow-up period (mean, 19.4 months), 14 of 73 (19.2%) patients developed biochemical recurrence. Expression of miR-96, -145 and -221 correlated strongly with each other, but there were no correlations between miRNA expression and clinicopathologic parameters. Kaplan-Meier survival curves using the log-rank test showed a decreased biochemical recurrence-free interval with pathologic stage (P<0.001). In addition, patients with Gleason scores over 8, compared with those with a Gleason score of 6, showed a decreased biochemical recurrence-free interval in Kaplan-Meier analysis (P=0.001). However, expression of miR-96, -145 and -221 did not correlate with the biochemical recurrence interval in Kaplan-Meier survival curves or by multivariate analysis using the Cox proportional hazard regression model, either. In conclusion, we did not observe a significant correlation between the expression of miR-96, -145 and -221 and clinicopathologic parameters. To utilize miRNA as a diagnostic tool in clinical practice, more research is needed to understand miRNA mechanisms, identify miRNA targets, and further characterize miRNA function.
Asian Journal of Andrology 08/2012; 14(5):752-7. · 2.14 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cryptogenic organizing pneumonia (COP) is an idiopathic interstitial pneumonia characterized by fibroblastic tissues that occupy the lumina of alveoli and alveolar ducts or respiratory bronchioles. Although adequate doses and durations of glucocorticoids can improve its condition, COP is sometimes resistant to glucocorticoid therapy and is often lethal.Herein, a very rare case of 'bronchiolar COP' that was confined to the respiratory bronchioles is reported. This case indicates that macrolides may act as anti-inflammatory agents in patients with COP. Timely and precise pathological diagnosis may corroborate clinician diagnoses and eventually improve chances to overcome the disease.
Pathology International 02/2012; 62(2):144-8. · 1.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To report a case of oxaliplatin-combined chemotherapy-induced interstitial lung disease.
A 57-year-old man was referred complaining of dyspnea and fever after treatment with an oxaliplatin-combined chemotherapeutic agent for metastatic colorectal cancer. Fever development and spontaneous subsidence were observed during the chemotherapeutic course repeatedly until the 9th cycle. A computer-tomographic (CT) scan revealed bilateral, peripherally distributed, patchy consolidation suggestive of an interstitial lung disease. As a confirmative step, video-assisted thoracoscopic surgical biopsy was attempted; the characteristic intraluminal organizing fibrous plug in the bronchioles and alveoli was seen. Corticosteroid therapy was administered, which rapidly improved the patient's symptoms and chest CT findings.
This case showed that oxaliplatin may be implicated in the etiology of interstitial lung disease, since withdrawal of the drug resulted in improvement of interstitial lung disease.
Medical Principles and Practice 01/2012; 21(1):89-92. · 0.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Distant metastasis and recurrence are major prognostic factors associated with breast cancer. Both lymphovascular invasion (LVI) and blood vessel invasion (BVI) are important routes for metastasis to regional lymph nodes and for systemic metastasis. Despite the importance of vascular invasion as a prognostic factor, application of vascular invasion as a histopathological criterion is controversial. The aim of this study was to distinguish LVI from BVI in prognosis and recurrence of breast cancer using an endothelial subtype specific immunohistochemical stain (podoplanin, D2-40, and CD31).
Sections from 80 paraffin-embedded archival specimens of invasive breast cancer were stained for podoplanin, D2-40, or CD31 expression. Immunohistochemical staining results were correlated with clinicopathological features, such as tumor size, status of lymph node metastases, estrogen receptor status, progesterone receptor status, human epidermal growth factor receptor-2 expression, and recurrence. Patients with ductal carcinoma in situ and stage IV breast cancer were excluded.
A significant correlation was found between D2-40 LVI positivity and lymph node metastasis (p=0.022). We found a significant correlation between D2-40 LVI positivity and recurrence of breast cancer (p=0.014). However, no significant correlation was found between BVI and recurrence. A poorer disease free survival was shown for D2-40 positive LVI (p=0.003). In a multivariate analysis, the presence of D2-40 LVI positivity revealed a significant association with decreased disease-free survival.
D2-40 LVI positivity was a more prognostic predictor of breast cancer than BVI.
[Show abstract][Hide abstract] ABSTRACT: We report a case of tuberous sclerosis associated with two histologically different renal cell carcinomas (RCCs) and multiple angiomyolipomas (AMLs) in the same kidney. A 43-year-old female was admitted to our hospital with left flank pain and a huge palpable mass in the left flank area. Abdominal computed tomography revealed two concurrent RCCs and multiple AMLs in the left kidney. Because of the clinical suspicion of RCC, the patient underwent left radical nephrectomy. On gross examination, the total size of the resected left kidney was 30.5×17×8 cm. Microscopically, the upper pole tumor features were consistent with chromophobe RCC and the midpole tumor was a clear-cell RCC. The multifocal masses in the remaining remnant parenchyma were AMLs. Six months after surgery, the patient is healthy without signs of tumor recurrence.
[Show abstract][Hide abstract] ABSTRACT: Dedifferentiated liposarcoma is a high-grade nonlipogenic sarcoma that arises in the background of a preexisting well-differentiated liposarcoma. The purpose of this work is to evaluate the spectrum of radiologic appearance of retroperitoneal dedifferentiated liposarcoma with clinicopathologic features.
Radiologic images and clinical histories of 15 patients with histologically verified retroperitoneal dedifferentiated liposarcoma were retrospectively studied. Patients included 11 men and 4 women, with mean age of 55.8 years (range, 36-74 years), and they underwent computed tomography (CT) (n=15) and magnetic resonance imaging (MRI) (n=5).
The mean size of the tumor was 22.6 cm with a range of 9.5-38 cm. Both CT and MRI showed well-circumscribed, large round, or lobulated retroperitoneal mass. The appearance of the tumor was classified as follows: Category I, nonfatty component within predominant fatty mass (n=5); Category II, focal fatty component within large nonfatty mass (n=6); Category III, well-defined fatty mass and well-defined nonfatty mass (n=1); Category IV, two masses with predominantly nonfatty component (n=3).
Retroperitoneal dedifferentiated liposarcomas present various spectra of imaging findings. While Categories I and III may suggest dedifferentiated liposarcoma, Categories II and IV may appear as other types of liposarcoma or other malignant retroperitoneal tumor.
[Show abstract][Hide abstract] ABSTRACT: To evaluate the characteristics of highly malignant soft tissue sarcoma of the extremity with a delayed diagnosis.
The clinical and radiological characteristics of 18 cases of highly malignant soft tissue sarcomas of the extremity with a delayed diagnosis were determined.
Ten men and eight women of mean age 44.8 years (range, 15-79 years) were included in this study. Seven cases of synovial sarcoma, three cases each of alveolar soft part sarcoma and malignant fibrous histiocytoma, two cases each of highly malignant leiomyosarcoma and myxofibrosarcoma, and one case of clear cell sarcoma were enrolled. Times from tumor detection to diagnosis ranged from 1 to 3 years in most cases; three of the seven synovial sarcoma cases took more than 10 years to diagnose. Of the seven cases of synovial sarcoma, five cases of small, superficial located masses were simply excised without a pre-surgical biopsy. Three cases of alveolar soft part sarcoma showed characteristic T1- and T2-weighted high signal intensities with signal voids in MR images. In addition, one synovial sarcoma patient and one alveolar soft part sarcoma patient showed evidence of calcification on plain radiographs. However, no general characteristic clinical findings were found to be common to the 18 cases.
Contrary to general expectations, some soft tissue tumors that grow slowly are painless, and those that occur in superficial limbs may be highly malignant. Thus, even when a slow growing, painless superficial mass is encountered in a limb, physicians should keep the possibility of highly malignant soft tissue sarcoma in mind.
World Journal of Surgical Oncology 01/2010; 8:84. · 1.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Biomarkers play a key role in risk assessment, assessing treatment response, and detecting recurrence and the investigation of multiple biomarkers may also prove useful in accurate prediction and prognosis of cancers. Immunohistochemistry (IHC) has been a major diagnostic tool to identify therapeutic biomarkers and to subclassify breast cancer patients. However, there is no suitable IHC platform for multiplex assay toward personalized cancer therapy. Here, we report a microfluidics-based multiplexed IHC (MMIHC) platform that significantly improves IHC performance in reduction of time and tissue consumption, quantification, consistency, sensitivity, specificity and cost-effectiveness.
By creating a simple and robust interface between the device and human breast tissue samples, we not only applied conventional thin-section tissues into on-chip without any additional modification process, but also attained perfect fluid control for various solutions, without any leakage, bubble formation, or cross-contamination. Four biomarkers, estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2), progesterone receptor (PR) and Ki-67, were examined simultaneously on breast cancer cells and human breast cancer tissues. The MMIHC method improved immunoreaction, reducing time and reagent consumption. Moreover, it showed the availability of semi-quantitative analysis by comparing Western blot. Concordance study proved strong consensus between conventional whole-section analysis and MMIHC (n = 105, lowest Kendall's coefficient of concordance, 0.90). To demonstrate the suitability of MMIHC for scarce samples, it was also applied successfully to tissues from needle biopsies.
The microfluidic system, for the first time, was successfully applied to human clinical tissue samples and histopathological diagnosis was realized for breast cancers. Our results showing substantial agreement indicate that several cancer-related proteins can be simultaneously investigated on a single tumor section, giving clear advantages and technical advances over standard immunohistochemical method. This novel concept will enable histopathological diagnosis using numerous specific biomarkers at a time even for small-sized specimens, thus facilitating the individualization of cancer therapy.
PLoS ONE 01/2010; 5(5):e10441. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Soft tissue sarcomas are a highly heterogeneous group of malignancies that arise from mesenchymal tissues. Grading of soft tissue sarcomas is an important prerequisite for the choice of therapy and estimation of prognosis. However, incisional biopsy of huge soft tissue sarcoma lesions frequently fails to provide an accurate diagnosis when there is a benign component, cystic changes and/or necrosis. MRI is helpful in evaluating the extent of the sarcoma lesion, vascularization, invasiveness and integrity of surrounding tissue, but definitive differentiation of benignity and malignancy is not possible with it. In this study, positron emission tomography using [(18)F]-2-fluoro-2-deoxy-D-glucose successfully guided surgeons to identify the most hypermetabolic and, therefore, the most suitable biopsy sites of huge soft tissue sarcoma.
Annals of Nuclear Medicine 10/2009; 23(10):887-9. · 1.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Mesonephric rests or mesonephric remnants are vestiges of embryonic structures called mesonephric (wolffian) ducts. It usually can be seen in the lateral wall of the cervix uteri. In males, the mesonephric remnants are seen in epididymis and efferent ductules. Prostate is one of the rare locations, on which the mesonephric remnants can be found. Hyperplasia of mesonephric remnants of prostate is rare but important because sometimes it is difficult to differentiate from adenocarcinoma. The lesion is important in the differential diagnosis from the high grade prostatic intraepithelial neoplasia. Here, we report an additional case of mesonephric hyperplasia, epididymal type, in a 66-year-old man. Microscopically, it showed tubular structures lined by columnar cells with pseudostratified elongated hyperchromatic nuclei. The cells showed negative reaction on high molecular weight cytokeratin and prostate-specific antigen immunostain.
Basic and Applied Pathology 04/2009; 2(2):69 - 71.