-
[show abstract]
[hide abstract]
ABSTRACT: OBJECTIVE: This study investigated the correlation of oestrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) status with the probability of malignancy (POM) of mammographic calcifications in ductal carcinoma in situ (DCIS). METHODS: A total of 101 women (age range, 27-83 years) with pure DCIS that presented as mammographic calcifications were included. Three radiologists independently reviewed mammograms according to the BI-RADS lexicon and provided 100-point POM scores and a BI-RADS category. ER, HER2 and breast cancer subtypes were determined using immunohistochemistry (IHC) and fluorescence in situ hybridisation. Pairwise correlations between POM and IHC biomarker scores were calculated, and mammographic features were compared between breast cancer subtypes. RESULTS: HER2 level positively correlated with the POM score (P < 0.0001) and BI-RADS category (P < 0.0001), and ER level inversely correlated with the POM score (P < 0.013) and BI-RADS category (P < 0.010). Fine linear branching (P = 0.004) and segmental (P = 0.014) calcifications were significantly associated with HER2-positive cancers, and clustered calcifications were more frequently observed in ER-positive cancers (P = 0.014). CONCLUSION: HER2 status in DCIS correlated positively with the POM of mammographic calcifications, as determined by radiologists on the basis of the BI-RADS lexicon. KEY POINTS : • Prediction of malignancy on mammographic ductal carcinoma in situ is difficult. • HER2 level correlated positively with the probability of malignancy assigned by radiologists. • ER level correlated inversely with the probability of malignancy assigned by radiologists. • HER2-positive DCIS more frequently exhibited fine linear branching or segmental calcifications. • ER-positive DCIS more frequently exhibited clustered calcifications.
European Radiology 03/2013; · 3.22 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Purpose:To retrospectively identify quantitative computed tomographic (CT) features that correlate with epidermal growth factor receptor (EGFR) mutation in surgically resected lung adenocarcinomas stratified by the International Association for the Study of Lung Cancer (IASLC), American Thoracic Society (ATS), and European Respiratory Society (ERS) classification in an East Asian cohort of patients known to have a high prevalence of EGFR mutations.Materials and Methods:An institutional review board approved this study and waived informed consent. In 153 surgically resected lung adenocarcinomas, EGFR mutation was determined by direct DNA sequencing. Histologic subtype was classified according to IASLC/ATS/ERS classification of lung adenocarcinoma. At preoperative chest CT, the percentage of ground-glass opacity (GGO) volume and total tumor volume of each tumor were measured by using a semiautomated algorithm. Distribution of EGFR mutation according to histologic subtype, percentage of GGO volume, and total tumor volume was evaluated by using the Fisher exact test, the Student t test, trend analysis, and multiple logistic regression analysis.Results:Exon 21 missense mutation was more frequent in lepidic predominant adenocarcinomas than in other histologic subtypes (odds ratio, 3.44; 95% confidence interval: 1.53, 7.74; P = .003). GGO volume percentage in tumors with exon 21 missense mutation (61.7% ± 31.9 [standard deviation]) was significantly higher than that in EGFR wild-type tumors (30.0% ± 38.5) (P = .0001) and exon 19-mutated tumors (28.9% ± 37.7) (P = .0006). A significant trend of prevalence of exon 21 missense mutation increasing along with increasing GGO volume (P = .0008) was found.Conclusion:GGO volume percentage in tumors with exon 21 missense mutation was significantly higher than that in tumors with other EGFR mutation status. This can be related to the fact that exon 21 missense mutation was significantly more frequent in lepidic predominant adenocarcinomas, including adenocarcinoma in situ, minimally invasive adenocarcinoma, and lepidic predominant invasive adenocarcinoma, according to IASLE/ATS/ERS classification.© RSNA, 2013Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.13112553/-/DC1.
Radiology 03/2013; · 5.73 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Abstract We analyzed clinicopathologic implication of A20/Tumor necrosis factor alpha-induced protein 3 deletion in diffuse large B-cell lymphoma (DLBCL) using fluorescence in situ hybridization, according to germinal center B-cell (GCB) vs. non-GCB/activated B-cell (ABC) phenotypes and rituximab treatment. Excluding primary CNS and EBV-positive lymphomas, 134 DLBCLs were analyzed. A20 was deleted in 23.1% (31/134) of DLBCLs containing 21.6% (29/134) of monoallelic and 1.5% (2/134) of biallelic deletion with no predilection for GCB vs. non-GCB/ABC. In univariate analysis, A20 deletion was marginally associated with good prognosis in rituximab-treated subgroup (n=109; p=0.0454), non-gastrointestinal lymphoma (n=108; p=0.0320) and nodal lymphoma (n=46; p=0.0411). In multivariate analysis in rituximab-treated DLBCL, MUM1 and international prognostic index (IPI) were independent prognostic factors (p=0.021 [IPI]; p=009 [MUM1]) with a marginal good prognostic effect for A20 deletion (p=0.047). Taken together, A20 deletion was observed in similar frequencies in GCB and non-GCB/ABC, and was not a poor prognostic factor in DLBCL.
Leukemia & lymphoma 01/2013; · 2.40 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND: Although activating epidermal growth factor receptor (EGFR) mutations are excellent predictors of gefitinib outcome in non-small-cell lung cancer (NSCLC), most patients become resistant to gefitinib. Despite our knowledge of the molecular basis of acquired resistance, clinical predictors have not been well elucidated. This study was undertaken to evaluate predictors of clinical outcome in patients with NSCLC and with EGFR mutations treated with gefitinib. PATIENTS AND METHODS: A total of 170 patients with NSCLC and with EGFR mutations received gefitinib as a first-line (n = 50) and a second-line or more (n = 120) treatment at Seoul National University Hospital. Treatment outcomes were compared between groups based on clinicopathologic factors, such as treatment line, metastatic site, and mutation subtype. RESULTS: Survival outcomes were similar between first-line and second-line or greater gefitinib treatment (overall response rate, 2P = .832; progression-free survival [PFS], 2P = .373; and overall survival [OS], 2P = .290). When the number of metastatic sites was at least 3, significantly reduced survival was observed (median PFS 8.5 vs. 14.0 months, 2P < .001; median OS 21.4 vs. 25.6 months, 2P = .002). In addition, the presence of at least 3 organs with metastases was an independent predictor of PFS (hazard ratio [HR] 1.97 [95% CI, 1.37-2.85]; 2P < .001) and OS (HR 2.00 [95% CI, 1.18-3.39]; 2P = .010). Patients who failed to respond to gefitinib within 6 months of treatment had more lymph node metastases and more sites of metastasis than those who responded later. CONCLUSIONS: Tumor burden, expressed as the number of metastatic sites, is predictive of inferior survival in patients with NSCLC and with activating EGFR mutations who are treated with gefitinib.
Clinical Lung Cancer 01/2013; · 2.94 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND:: The presence of mutation in EGFR gene is known as a predictive marker for the response to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment. However, whether or not these EGFR mutations are prognostic factors for non-small-cell lung cancer (NSCLC) is debatable. METHODS:: We retrospectively collected a series of samples from patients whose EGFR mutation status had been tested, and analyzed their survival. The pathologic cell types of 863 patients (520 men, 343 women) were squamous cell carcinoma in 227, adenocarcinoma in 636 patients. RESULTS:: EGFR mutations were detected in 354 patients and it was frequently observed in adenocarcinoma in younger, early-stage, female never-smokers. In univariate analysis of younger, early-stage, never-smoker women, bronchioloalveolar carcinoma pattern and the presence of EGFR mutation showed better long-term survival. However, in multivariate analysis, age, pathologic stage, and smoking status remained significant prognostic factors, whereas EGFR mutation was not. For recurrence, pathologic stage was the only independent prognostic factor. After recurrence, smoking status was the only significant risk factor that affected postrecurrence survival. However, when EGFR TKIs were used in EGFR-mutated patients, survival was longer than for those treated with conventional chemotherapy. CONCLUSIONS:: Although the EGFR mutation is a predictive marker for EGFR TKI response, it is not a prognostic factor in NSCLC. The clinical observation that patients with EGFR mutation seem to survive longer may be because EGFR mutation is more frequently associated with other good prognostic factors. Once there is a recurrence, administration of EGFR TKI for patients with EGFR mutation may increase survival.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 01/2013; · 4.55 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: MicroRNAs (miRNAs) participate in diverse biological functions and carcinogenesis by inhibiting specific gene expression. We previously reported that suppression of adenine nucleotide translocase 2 (ANT2) by using the short hairpin RNA (shRNA) approach has an antitumor effect in several cancer cells. We here examined the influence of ANT2 on expression of miRNAs in hepatocellular carcinoma (HCC) to further elucidate the tumor-suppressive mechanism of ANT2 shRNA. We first carried out screening for miRNAs, whose expression is regulated by ANT2 suppression in the Hep3B HCC cell line using miRNA microarrays. Validation of candidate miRNAs was done by incorporating clinical samples, and their effects on the tumorigenesis of HCC were studied in vitro and in vivo. miR-636 was one of the miRNAs whose expression was highly upregulated by ANT2 suppression in miRNA microarray analysis, as confirmed by real-time reverse transcription-polymerase chain reaction. Notably, miR-636 was markedly downregulated in HCC tissues compared with matched non-neoplastic liver in clinical samples. Restoration of miR-636 in Hep3B cells led to significant reduction of cell proliferation and colony formation. miR-636 restoration resulted in a decreased level of Ras, one of the putative targets of miR-636, and inactivation of its signaling pathway. Moreover, tumorigenesis was efficiently suppressed by miR-636 in an in vivo tumor xenograft model of HCC. The data suggest that miR-636 might function as a tumor suppressor miRNA affecting HCC tumorigenesis via downregulation of Ras, and that ANT2 suppression by shRNA could exert an anticancer effect by restoring miR-636 expression in HCC.
Experimental & molecular medicine. 01/2013; 45:e3.
-
[show abstract]
[hide abstract]
ABSTRACT: To identify CT and FDG-PET features associated with epidermal growth factor receptor (EGFR) protein overexpression, and to evaluate whether imaging features and EGFR-overexpression can help predict clinical outcome.
In 214 patients (M : F = 129 : 85; mean age, 63.2) who underwent curative resection of stage I non-small cell lung cancer, EGFR protein expression status was determined through immunohistochemical analysis. Imaging characteristics on CT and FDG-PET was assessed in relation to EGFR-overexpression. Imaging features and EGFR-overexpression were also evaluated for clinical outcome by using the Cox proportional hazards model.
EGFR-overexpression was found in 51 patients (23.8%). It was significantly more frequent in tumors with an SUVmax > 5.0 (p < 0.0001), diameter > 2.43 cm (p < 0.0001), and with ground glass opacity ≤ 50% (p = 0.0073). SUVmax > 5.0 (OR, 3.113; 95% CI, 1.375-7.049; p = 0.006) and diameter > 2.43 cm (OR, 2.799; 95% CI, 1.285-6.095; p = 0.010) were independent predictors of EGFR overexpression. Multivariate analysis showed that SUVmax > 4.0 (hazard ratio, 10.660; 95% CI, 1.370-82.966; p = 0.024), and the presence of cavitation within a tumor (hazard ratio, 3.122; 95% CI, 1.143-8.532; p = 0.026) were factors associated with poor prognosis.
EGFR-overexpression is associated with high SUVmax, large tumor diameter, and small GGO proportion. CT and FDG-PET findings, which are closely related to EGFR overexpression, can be valuable in the prediction of clinical outcome.
Korean journal of radiology: official journal of the Korean Radiological Society 01/2013; 14(2):375-383. · 1.32 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Suppressor of cytokine signaling 1 (SOCS1) is a negative regulator of Janus kinase and the signal transducer and activation of transcription (Jak-STAT) pathway. SOCS-1 is known to be silenced by aberrant promoter methylation in human hepatocellular carcinoma (HCC) during early tumorigenesis, therefore, a strategy to restore SOCS1 expression can be utilized for cancer therapy. Here, we examined the influence of adenine nucleotide translocase 2 (ANT2) suppression by short-hairpin RNA (shRNA) on SOCS1 expression and its downstream effect in HCC. ANT2 shRNA treatment led to restoration of SOCS1 expression along with its promoter demethylation in Hep3B cells, which was accompanied by decreased DNA methyltransferase 1 (DNMT1) activity through the suppression of Ras/PI3K/Akt signaling. Restoration of SOCS1 by ANT2 knockdown, subsequently, inhibited STAT3 activity and downregulated the expression of miR-21, which has been reported to be an important onco-miR in HCC. Downregulation of miR-21 efficiently suppressed Hep3B cell proliferation in vitro with a comparable level to ANT2 shRNA treatment. ANT2 suppression by shRNA may be able to exert anticancer effects in HCC further by restoring SOCS1 expression.
International Journal of Oncology 12/2012; · 2.40 Impact Factor
-
Tae Min Kim,
Jin Chul Paeng,
In Kook Chun,
Bhumsuk Keam, Yoon Kyung Jeon,
Se-Hoon Lee,
Dong-Wan Kim,
Dong Soo Lee,
Chul Woo Kim,
June-Key Chung,
Il Han Kim,
Dae Seog Heo
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND: This study was undertaken to evaluate the prognostic value of quantitative metabolic parameters in [(18) F]2-fluoro-2-deoxyglucose (FDG)-positron emission tomography (PET) for diffuse large B cell lymphoma (DLBCL). METHODS: A total of 140 DLBCL patients underwent FDG-PET scans before rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) chemotherapy. The maximal standardized uptake value (SUV(max) ) and total lesion glycolysis (TLG) were calculated, with the margin thresholds as 25%, 50%, and 75% of SUV(max) of all lesions. Treatment outcomes were compared between groups according to metabolic parameters and the International Prognostic Index (IPI). RESULTS: After a median follow-up of 28.5 months (range, 5-81 months), the 2-year progression-free survival (PFS) and overall survival (OS) were 83% and 87%, respectively. Among metabolic parameters, TLG at the threshold of 50% (TLG(50) ) was significantly associated with treatment outcomes. High TLG(50) values (>415.5) were associated with reduced survivals compared with low TLG(50) values (≤415.5) (2-year PFS of 73% versus 92%, P = .007; and 2-year OS of 81% versus 93%, P = .031). High IPI score (≥3) significantly reduced OS (2-year OS of 79% versus 90%, P = .049). Ann Arbor stage III/IV adversely affected PFS (P = .013). However, high IPI score and Ann Arbor stage of III/V did not significantly shorten PFS (P = .200) and OS (P = .921), respectively. High TLG(50) values independently predicted survivals by multivariate analysis (hazard ratio = 4.4; 95% confidence interval = 1.5-13.1; P = .008 for PFS and hazard ratio = 3.1; 95% confidence interval = 1.0-9.6; P = .049 for OS). CONCLUSIONS: Combined assessment of volume and metabolism (ie, TLG) is predictive of survivals in DLBCL patients who are treated with R-CHOP. Cancer 2012. © 2012 American Cancer Society.
Cancer 12/2012; · 4.77 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To describe our initial experience with CT-guided percutaneous barium marking for the localization of small pulmonary nodules prior to video-assisted thoracoscopic surgery (VATS).
From October 2010 to April 2011, 10 consecutive patients (4 men and 6 women; mean age, 60 years) underwent CT-guided percutaneous barium marking for the localization of 10 small pulmonary nodules (mean size, 7.6 mm; range, 3-14 mm): 6 pure ground-glass nodules, 3 part-solid nodules, and 1 solid nodule. A 140% barium sulfate suspension (mean amount, 0.2 mL; range, 0.15-0.25 mL) was injected around the nodules with a 21-gauge needle. The technical details, surgical findings and pathologic features associated with barium localizations were evaluated.
All nodules were marked within 3 mm (mean distance, 1.1 mm; range, 0-3 mm) from the barium ball (mean diameter, 9.6 mm; range, 8-16 mm) formed by the injected barium suspension. Pneumothorax occurred in two cases, for which one needed aspiration. However, there were no other complications. All barium balls were palpable during VATS and visible on intraoperative fluoroscopy, and were completely resected. Both the whitish barium balls and target nodules were identifiable in the frozen specimens. Pathology revealed one invasive adenocarcinoma, five adenocarcinoma-in-situ, two atypical adenomatous hyperplasias, and two benign lesions. In all cases, there were acute inflammations around the barium balls which did not hamper the histological diagnosis of the nodules.
CT-guided percutaneous barium marking can be an effective, convenient and safe pre-operative localization procedure prior to VATS, enabling accurate resection and diagnosis of small or faint pulmonary nodules.
Korean journal of radiology: official journal of the Korean Radiological Society 11/2012; 13(6):694-701. · 1.32 Impact Factor
-
Ji-Won Kim,
Jee Hyun Kim,
Seock-Ah Im,
Yu Jung Kim,
Hye-Suk Han,
Jin-Soo Kim,
Sae-Won Han, Yoon Kyung Jeon,
Do-Youn Oh,
Wonshik Han,
Tae-You Kim,
In Ae Park,
Dong-Young Noh,
Yung-Jue Bang
[show abstract]
[hide abstract]
ABSTRACT: Objective: The aim of this study was to elucidate clinical implications of ABCB1, FCGR2A, and FCGR3A polymorphisms in patients with HER2-positive metastatic breast cancer (MBC) after taxane plus trastuzumab (TH) chemotherapy. Methods: Using genomic DNA samples extracted from mononuclear cells of consecutive patients with HER2-positive MBC who received first-line TH, we analyzed five polymorphisms (ABCB1 1236C>T, ABCB1 2677G>T/A, ABCB1 3435C>T, FCGR2A 131H/R, and FCGR3A 158V/F) and then correlated them with the response rate, progression-free survival (PFS), overall survival (OS), and adverse events of patients. Results: A total of 57 women were analyzed. The median age was 46 years (range 27-72). ABCB1 2677T carriers had a longer PFS (p = 0.037) along with a tendency toward a longer OS (p = 0.057). ABCB1 3435CC genotype carriers had a shorter PFS (p = 0.039) along with a tendency toward a shorter OS (p = 0.093). In combined analysis, PFS was significantly longer in ABCB1 1236CC and/or 2677TT carriers compared to the others (p = 0.006). FCGR2A 131H/R and FCGR3A 158V/F polymorphisms were not significantly associated with response rate, PFS, and OS. Conclusions: Our data support that ABCB1 polymorphisms may predict PFS after first-line TH chemotherapy in patients with HER2-positive MBC. In contrast, FCGR2A 131H/R and FCGR3A 158V/F polymorphisms could not predict treatment outcomes.
Oncology 08/2012; 83(4):218-27. · 2.27 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Langerhans cell histiocytosis (LCH) is the collective designation for a group of proliferative disorders of antigen-presenting cells in the epidermis. Over the past several decades, the etiology of LCH has been a controversial issue, particularly with respect to the pathologic process, that is, whether it is a neoplastic or inflammatory process. Recently, it was reported that the JL1 epitope, which encompasses the nonglycosylation site of CD43, is only exposed in the precursor stages of hematopoietic cells or in neoplastic conditions. We sought to investigate the possible utility of the JL1 monoclonal antibody as a diagnostic marker of LCH. In this study, we compared the staining characteristics of antibodies against the JL1 epitope with those of langerin and CD1a, which are widely used for the diagnosis of LCH. We found substantial differences in the staining patterns of these markers. The JL1 epitope could be bound by antibodies in cases of LCH and Langerhans cell (LC) sarcoma. In non-neoplastic lesions, JL1-positive LCs were found only in dermatitis, reflecting the immaturity of LCs in inflamed skin. However, anti-langerin antibodies were able to identify any form of LC, including those in normal skin, dermatitis, dermatopathic lymphadenopathy, and LCH. On the basis of these findings, we propose that the anti-JL1 antibody is a specific marker of immaturity, a feature that is shared in neoplastic LCs, and can be useful in the diagnosis of LCH.
The American journal of surgical pathology 08/2012; 36(8):1150-7. · 4.06 Impact Factor
-
June Koo Lee,
Tae Min Kim,
Youngil Koh,
Se-Hoon Lee,
Dong-Wan Kim, Yoon-Kyung Jeon,
Doo Hyun Chung,
Seok-Chul Yang,
Young Tae Kim,
Young-Whan Kim,
Dae Seog Heo,
Yung-Jue Bang
[show abstract]
[hide abstract]
ABSTRACT: Epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) translocations in non-small cell lung cancer (NSCLC) are mutually exclusive. However, several exceptional cases harboring both genetic alterations have been reported. In this study, a total of 444 patients with lung adenocarcinoma were examined for their EGFR and ALK status at Seoul National University Hospital between July 2008 and September 2011. EGFR mutations and ALK translocations were detected in 228 (51.4%) and 34 (7.7%) patients, respectively. Four patients (0.9%) had both genetic alterations and three underwent curative surgery. One patient who received both EGFR tyrosine kinase and ALK inhibitors, separately showed an objective response to the ALK inhibitor alone. Considering our and previous studies, patients harboring both EGFR mutation and ALK translocation showed differential sensitivities to both targeted therapies, suggesting a variable dependence on EGFR and ALK oncogenes.
Lung cancer (Amsterdam, Netherlands) 05/2012; 77(2):460-3. · 3.14 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Fluorescence in situ hybridization (FISH) is currently used to detect non-small cell lung cancer (NSCLC) patients with anaplastic lymphoma kinase (ALK) gene rearrangement, who are candidates for ALK inhibitor therapy. However, FISH may not be a practical method for screening for ALK-positive patients in a large population due to its cost and difficulty in interpretation. We investigated the role of immunohistochemistry (IHC) to screen for ALK rearrangement in advanced NSCLC. We identified 1,166 stage IIIB or IV NSCLC patients with non-squamous histology from the Seoul National University Hospital NSCLC database. To enrich ALK-positive cases, we selected 262 patients who were either EGFR wild-type or non-responders to previous EGFR tyrosine kinase inhibitors (TKI). ALK IHC and ALK FISH were performed on formalin-fixed, paraffin-embedded tissue. ALK protein was expressed in 28 (10.7%) tumors in 262 patients. ALK FISH was positive in 25 (9.5%) cases. All patients with IHC score of 3 (n=9) were FISH-positive and all patients with score of 0 (n=234) were FISH-negative. Among patients with IHC scores of 1 and 2, five (83.3%, 5/6) and eleven (84.6%, 11/13) were FISH-positive, respectively. The sensitivity and specificity of ALK IHC with intensity score of 1 or more were 100% and 98.7%, respectively. IHC can be a useful test for screening ALK FISH-positive cases in advanced NSCLC. FISH testing should be considered for advanced NSCLC patients with tumors showing mild to moderate staining for ALK by IHC to confirm ALK translocation.
Lung cancer (Amsterdam, Netherlands) 03/2012; 77(2):288-92. · 3.14 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Making a differential diagnosis of IgG4-related disease from mucosa-associated lymphoid tissue (MALT) lymphoma or any other chronic inflammation is often challenging. Moreover, the association with secondary lymphoma of ocular adnexal IgG4-related disease needs to be elucidated.
We investigated 14 cases of IgG4-related disease, nine MALT lymphomas and 12 other chronic inflammations involving the lacrimal gland and orbit. Bilateral involvement was frequent in IgG4-related diseases. The number of IgG4-positive cells and the ratio of IgG4/IgG-positive cells were higher in patients with IgG4-related disease than in those with MALT lymphoma (P = 0.016; P < 0.001) and other types of inflammation (P < 0.001; P < 0.001). Monoclonal B cell proliferation was suspected in two cases (14.3%) of IgG4-related disease. One of these patients also displayed monomorphous features suggesting secondary MALT lymphoma. In the other case, κ-chain restriction in IgG4-positive cells was observed, raising the possibility of IgG4-producing MALT lymphoma. Trisomy 3, trisomy 18 or MALT1 translocation was observed in none of the IgG4-related cases. Regulatory T-cell infiltration was higher in cases of IgG4-related disease than in MALT lymphomas (P < 0.001) and other types of inflammation (P = 0.006).
Some genetically and morphologically complicated cases of ocular adnexal IgG4-related disease emphasize the need for in-depth studies to differentiate this disease from MALT lymphoma, and to exclude secondary lymphoma.
Histopathology 01/2012; 60(2):296-312. · 3.08 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Cancer stem cells (CSCs) are resistant to chemo- and radio-therapy, and can survive to regenerate new tumors. This is an important reason why various anti- cancer therapies often fail to completely control tumors, although they kill and eliminate the bulk of cancer cells. In this study, we determined whether or not adenine nucleotide translocator-2 (ANT2) suppression could also be effective in inducing cell death of breast cancer stem-like cells. A sub-population (SP; CD44+/ CD24-) of breast cancer cells has been reported to have stem/progenitor cell properties. We utilized the adeno- ANT2 shRNA virus to inhibit ANT2 expression and then observed the treatment effect in a SP of breast cancer cell line. In this study, MCF7, MDA-MB-231 cells, and breast epithelial cells (MCF10A) mesenchymally-transdifferentiated through E-cadherin knockdown were used. ANT2 expression was high in both stem-like cells and non-stem-like cells of MCF7 and MDA-MB-231 cells, and was induced and up-regulated by mesenchymal transdifferentiation in MCF10A cells (MCF10A(EMT)). Knockdown of ANT2 by adeno-shRNA virus efficiently induced apoptotic cell death in the stem-like cells of MCF7 and MDA-MB-231 cells, and MCF10A(EMT). Stem-like cells of MCF7 and MDA-MB-231, and MCF10A(EMT) cells exhibited increased drug (doxorubicin) resistance, and expressed a multi-drug resistant related molecule, ABCG2, at a high level. Adeno-ANT2 shRNA virus markedly sensitized the stem-like cells of MCF7 and MDA-MB-231, and the MCF10A(EMT) cells to doxorubicin, which was accompanied by down-regulation of ABCG2. Our results suggest that ANT2 suppression by adeno-shRNA virus is an effective strategy to induce cell death and increase the chemosensitivity of stem-like cells in breast cancer.
Experimental and Molecular Medicine 12/2011; 44(4):251-9. · 2.48 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The BRAF(V600E) mutation is the most common genetic alteration found in papillary thyroid cancer (PTC). Recent studies show that this mutation occurs more frequently in patients with PTC showing aggressive clinicopathologic features. The aim of the present study was to evaluate the prevalence of the BRAF(V600E) mutation in tumor samples and its association with high-risk clinicopathologic features prospectively.
From February 2009 to January 2010, 547 PTC patients who underwent surgery in Seoul National University Hospital were enrolled in the study. Polymerase chain reaction was used to amplify exon 15 of the BRAF gene from paraffin-embedded thyroid tumor specimens, followed by direct sequencing to detect the BRAF(V600E) mutation. Both univariate and multivariate analyses were performed to analyze associations between the BRAF(V600E) mutation and clinicopathologic features.
The BRAF(V600E) mutation was found in 381/547 (69.7%) patients with primary PTC. The BRAF(V600E) mutation was significantly associated with age (≥ 45 years), tumor size (>1 cm), extrathyroidal extension, and cervical lymph node metastases (P < 0.05). Multiple logistic regression showed that it was significantly associated with gender (OR = 1.834; 95% CI 1.021-3.463), tumor size (OR = 1.972; 95% CI 1.250-3.103), and extra-thyroidal extension (OR = 2.428; 95% CI 1.484-3.992), but not with age, multifocality, lymph node metastases, and advanced disease stage. The proportion of BRAF(V600E) mutation was significantly associated with the number of high-risk factors of tumor recurrence (P < 0.001).
The BRAF(V600E) mutation was associated with high-risk clinicopathologic characteristics in patients with PTC. The BRAF(V600E) mutation may be a potential prognostic factor in PTC patients.
World Journal of Surgery 12/2011; 36(2):310-7. · 2.36 Impact Factor
-
Kyeong Cheon Jung,
Chung-Gyu Park, Yoon Kyung Jeon,
Hyo Jin Park,
Young Larn Ban,
Hye Sook Min,
Eun Ji Kim,
Ju Hyun Kim,
Byung Hyun Kang,
Seung Pyo Park, [......],
Il-Hee Yoon,
Yong-Hee Kim,
Jae-Il Lee,
Jung-Sik Kim,
Jun-Seop Shin,
Jaeseok Yang,
Sung Joo Kim,
Emily Rostlund,
William A Muller,
Seong Hoe Park
[show abstract]
[hide abstract]
ABSTRACT: Induction of antigen-specific T cell tolerance would aid treatment of diverse immunological disorders and help prevent allograft rejection and graft versus host disease. In this study, we establish a method of inducing antigen-specific T cell tolerance in situ in diabetic humanized mice and Rhesus monkeys receiving porcine islet xenografts. Antigen-specific T cell tolerance is induced by administration of an antibody ligating a particular epitope on ICAM-1 (intercellular adhesion molecule 1). Antibody-mediated ligation of ICAM-1 on dendritic cells (DCs) led to the arrest of DCs in a semimature stage in vitro and in vivo. Ablation of DCs from mice completely abrogated anti-ICAM-1-induced antigen-specific T cell tolerance. T cell responses to unrelated antigens remained unaffected. In situ induction of DC-mediated T cell tolerance using this method may represent a potent therapeutic tool for preventing graft rejection.
Journal of Experimental Medicine 11/2011; 208(12):2477-88. · 13.85 Impact Factor
-
June Koo Lee,
Heae Surng Park,
Dong-Wan Kim,
Kimary Kulig,
Tae Min Kim,
Se-Hoon Lee, Yoon-Kyung Jeon,
Doo Hyun Chung,
Dae Seog Heo,
Woo-Ho Kim,
Yung-Jue Bang
[show abstract]
[hide abstract]
ABSTRACT: The purpose of this study was to investigate the overall survival (OS) of patients with advanced ALK-positive nonsmall cell lung cancer (NSCLC) who were managed in the pre-ALK inhibitor era and to compare their survival with that of a matched case cohort of ALK wild-type (WT) patients.
Data from 1166 patients who had stage IIIB/IV NSCLC with nonsquamous histology were collected from the NSCLC database of Seoul National University Hospital between 2003 and 2009. ALK fluorescence in situ hybridization (FISH) was used to analyze 262 patients who either had the WT epidermal growth factor receptor (EGFR) or were nonresponders to previous EGFR tyrosine kinase inhibitor (TKI) therapy. Overall survival (OS) was compared between 3 groups: 1) ALK-positive patients, 2) EGFR mutation-positive patients, and 3) ALK-WT/EGFR-WT patients. Progression-free survival (PFS) after first-line chemotherapy and EGFR TKIs also was analyzed.
Twenty-three patients were ALK-positive according to FISH analysis and did not receive ALK inhibitors during follow-up. The median OS for ALK-positive patients, EGFR mutation-positive patients, and WT/WT patients was 12.2 months, 29.6 months, and 19.3 months, respectively (vs EGFR mutation-positive patients, P = .001; vs WT/WT, P = .127). The PFS after first-line chemotherapy for the 3 groups was not different. However, the PFS for patients who received EGFR TKIs was shorter in ALK-positive patients compared with the other 2 groups (vs EGFR mutation-positive patients, P < .001; vs WT/WT, P < .021).
In the pre-ALK inhibitor era, ALK-positive patients experienced the shortest survival, although it did not differ statistically from that of WT/WT patients. Although their responses to platinum-based chemotherapy were not different from comparator groups, ALK-positive patients were even more resistant to EGFR TKI treatment than WT/WT patients.
Cancer 11/2011; 118(14):3579-86. · 4.77 Impact Factor
-
Journal of clinical rheumatology: practical reports on rheumatic & musculoskeletal diseases 10/2011; 17(7):392-4. · 1.19 Impact Factor
