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J K Lee,
J-Y Shin,
S Kim,
S Lee,
C Park,
J-Y Kim,
Y Koh,
B Keam,
H S Min,
T M Kim, Y-K Jeon,
D-W Kim,
D H Chung,
D S Heo,
S-H Lee,
J-I Kim
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ABSTRACT: Background
The mechanism of primary resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in EGFR-mutant non-small-cell lung cancer (NSCLC) has not been clearly understood.Patients and methodsEleven patients exhibiting primary resistance (disease progression <3 months) were identified among 197 consecutive NSCLC patients with TKI-sensitive EGFR mutations who received EGFR TKIs at Seoul National University Hospital. Treatment-naïve tumors were examined for concurrent genetic alterations using fluorescence in situ hybridization and targeted deep sequencing of cancer-related genes. Deletion polymorphism of Bcl-2-interacting mediator of cell death (BIM) gene was examined to validate its predictive role for TKI outcome.ResultsThe median progression-free survival (PFS) for patients receiving EGFR TKIs was 11.9 months, and the response rate 78.8%. Among the 11 patients exhibiting primary resistance, a de novo T790M mutation was identified in one patient, and two exhibited mesenchymal-epithelial transition amplification and anaplastic lymphoma kinase fusion. Targeted deep sequencing identified no recurrent, coexistent drivers of NSCLC. Survival analysis revealed that patients with recurrent disease after surgery had a longer PFS than those with initial stage IV disease. However, BIM deletion polymorphism, line of treatment, EGFR genotype, and smoking were not predictive of PFS for EGFR TKIs.Conclusions
We identified coexistent genetic alterations of cancer-related genes that could explain primary resistance in a small proportion of patients. Our result suggests that the mechanism of primary resistance might be heterogeneous.
Annals of Oncology 04/2013; · 6.43 Impact Factor
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ABSTRACT: To examine the role of the -667G/T, -618A/C and -148G/C single nucleotide polymorphisms in the promoter region of the human interleukin (IL) 18 gene in the development of pulmonary tuberculosis (PTB), and its radiographic characteristics and severity.
Differences in the allele and genotype distributions of the -667G/T, -618A/C, and -148G/C polymorphisms between 251 patients with PTB and 225 healthy controls, between patients with single- and multilobe involvement, and between patients with and without cavities were explored. Serum IL-18 levels were measured using an enzyme-linked immunosorbent assay.
The -148G/G genotype was more common in patients with cavities than in those without (82.8% vs. 70.9%, P = 0.04), but an analogous trend was not observed for the -667G/T and -618A/C genotypes. However, there were no significant differences in allele and genotype distributions between patients with PTB and healthy controls, or between patients with single- and multilobe involvement (P > 0.05). Serum IL-18 levels were higher in patients with cavities (P = 0.01) and in patients with the -148G/G genotype (P = 0.02).
Considering serum IL-18 levels, the -148G/G genotype is associated with a cavitary formation of PTB rather than its development.
The international journal of tuberculosis and lung disease: the official journal of the International Union against Tuberculosis and Lung Disease 09/2011; 15(9):1246-51, i. · 2.73 Impact Factor
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ABSTRACT: OBJECTIVE: To examine the role of the −667G/T, −618A/C and −148G/C single nucleotide polymorphisms in the promoter region of the human interleukin (IL) 18 gene in the development of pulmonary tuberculosis (PTB), and its radiographic characteristics and severity.DESIGN: Differences in the allele and genotype distributions of the −667G/T, −618A/C, and −148G/C polymorphisms between 251 patients with PTB and 225 healthy controls, between patients with single- and multilobe involvement, and between patients with and without cavities were explored. Serum IL-18 levels were measured using an enzyme-linked immunosorbent assay.RESULTS: The −148G/G genotype was more common in patients with cavities than in those without (82.8% vs. 70.9%, P = 0.04), but an analogous trend was not observed for the −667G/T and −618A/C genotypes. However, there were no significant differences in allele and genotype distributions between patients with PTB and healthy controls, or between patients with single- and multilobe involvement (P > 0.05). Serum IL-18 levels were higher in patients with cavities (P = 0.01) and in patients with the −148G/G genotype (P = 0.02).CONCLUSION: Considering serum IL-18 levels, the −148G/G genotype is associated with a cavitary formation of PTB rather than its development.
The international journal of tuberculosis and lung disease: the official journal of the International Union against Tuberculosis and Lung Disease 08/2011; 15(9):1246-1251. · 2.73 Impact Factor
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British Journal of Dermatology 04/2010; 163(3):651-3. · 3.67 Impact Factor
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Y Koh,
T M Kim, Y K Jeon,
T-K Kwon,
J H Hah,
S-H Lee,
D-W Kim,
H-G Wu,
C-S Rhee,
M-W Sung,
C W Kim,
K H Kim,
D S Heo
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ABSTRACT: Recent researches revealed that class III beta-tubulin (TUBB3) is a prognostic marker in various tumors and role of TUBB3 in head and neck squamous cell carcinoma (HNSCC) is not defined yet. We analyzed the significance of TUBB3 expression along with p53 and ERCC1 in locally advanced HNSCC patients receiving cisplatin-based induction chemotherapy.
Retrospective review of medical records at Seoul National University Hospital between 1998 and 2007 was carried out. Immunohistochemical stain of TUBB3, p53, and ERCC1 was done in paraffin-embedded tumor tissue. We assessed response to treatment, progression-free survival (PFS), overall survival (OS), and cancer-specific survival (CSS).
Eighty-five patients with oropharyngeal, hypopharyngeal, and laryngeal cancers received induction chemotherapy with 5-fluorouracil (5-FU) and cisplatin (n = 55), or 5-FU, cisplatin, and docetaxel (Taxotere) (n = 30). Eighty-three received definitive treatment after induction chemotherapy, where 62 received radiotherapy and 21 received surgery. TUBB3-positive patients showed lower response rate than TUBB3-negative patients (69% versus 88%, P = 0.039). Shorter median PFS was observed in TUBB3-positive group (12 versus 47 months, P = 0.001). Shorter median OS was observed in TUBB-positive group not reaching statistical significance (30 versus 59 months, P = 0.072). TUBB3 status significantly influenced CSS (35 months versus not reached, P = 0.017). Positive p53 status was related to poorer OS and CSS. ERCC1 showed no influence on chemotherapy response, PFS, OS, and CSS.
TUBB3 is a predictive and prognostic marker along with well-known p53 in HNSCC patients receiving cisplatin-based induction chemotherapy. Clinical impact of ERCC1 is not evident in this setting.
Annals of Oncology 06/2009; 20(8):1414-9. · 6.43 Impact Factor
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ABSTRACT: Extranodal natural killer/T-cell lymphoma (NKTCL) is a clinically heterogeneous disease with a poor prognosis, requiring risk-stratified management in affected patients. Recently, tumor microenvironment including regulatory T cells (Tregs) has been implicated as a prognostic marker in certain types of lymphoma.
We collected 64 NKTCL cases and numerically quantified the amount of tumor-infiltrating FOXP3-positive Tregs by automated slide scanning and image analysis program after immunohistochemical staining using anti-FOXP3 antibody.
Patients were able to be classified into two end groups by their level of Tregs. Twenty-eight (44%) patients had Tregs <50/0.40 mm(2), while 36 (56%) had Tregs > or =50/0.40 mm(2) within the tumor. The decreased number of Tregs (<50/0.40 mm(2)) was more common in patients with poor performance status or in those presented in non-upper aerodigestive tract. However, the level of Tregs was not associated with other prognostic factors, including stage, lactate dehydrogenase level, International Prognostic Index, and NKTCL Prognostic Index. Importantly, patients with increased numbers of Tregs (> or =50/0.40 mm(2)) showed prolonged overall and progression-free survival (P = 0.0005 and P = 0.0079, respectively). The number of FOXP3-positive Tregs was an independent prognostic factor (P = 0.001) by multivariate analysis.
Increased quantity of tumor-infiltrating Tregs predicted improved clinical outcome in NKTCL patients.
Annals of Oncology 06/2009; 20(10):1688-96. · 6.43 Impact Factor
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ABSTRACT: There has been no clear evidence demonstrating whether DNA hypermethylation can affect the prognosis of esophageal cancer. We collected tissue from 50 cases of squamous cell carcinoma of the esophagus and tested them for DNA hypermethylation using methylation-specific polymerase chain reaction. CpG island hypermethylations were observed in 10% for p16, 34% for RARbetaP2, 46% for adenomatosis polyposis coli (APC), 14% for RASSF1A, 84% for FHIT, and 8% for hMLH1. APC promoter hypermethylation was frequently found in patients without lymph node metastasis compared with those with lymph node metastasis (62.5% : 30.8%, P = 0.025). The number of metastatic lymph nodes were lower in patients with APC promoter hypermethylation (0.87 +/- 0.30 : 3.07 +/- 0.72, P = 0.008). Excluding operative mortalities and incomplete resections, 42 patients were analyzed for long-term outcome. During the mean follow-up period of 35 months, 17 developed recurrence and 14 died of cancer. Ten patients died of other causes. In univariable analysis, unmethylation of APC (P = 0.0015) and FHIT (P = 0.0044), as well as presence of lymph node metastasis (P = 0.0038), were risk factors for recurrence. In multivariable analysis, lymph nodes metastasis (P = 0.050) and unmethylation of APC promoter (P = 0.023) remained as significant risk factors. In conclusion, promoter hypermethylation of the APC gene is related to a lower number of metastatic lymph nodes and to superior prognosis in terms of recurrence, which suggests it might be involved in the process of lymph node metastasis in esophageal cancer.
Diseases of the Esophagus 11/2008; 22(2):143-50. · 1.81 Impact Factor
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ABSTRACT: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease with various genetic alterations. The aim was to investigate MYC, Bcl-2 and Bcl-6 translocations and copy number changes in adult DLBCLs to evaluate their clinicopathological features and prognostic implications.
Gene status was examined using fluorescence in situ hybridization (FISH), and the results were analysed in the context of germinal centre B-cell (GCB) and non-GCB type of DLBCL based on immunohistochemistry. MYC translocation was observed in 9% (14 of 156), and an increased copy number (ICN) in 7.1% (11 of 156). MYC translocation was more common in GCB type (22%) than in non-GCB type (4.9%), and associated with advanced International Prognostic Index (IPI). MYC aberration, i.e. translocation or increased copy number (ICN), was significantly associated with shorter overall survival, especially for the GCB type. Bcl-2 translocation was rare (3.4%, five of 145), and ICN was observed in 11.7% (17 of 145), more frequently in non-GCB type (16%) than in GCB type (2.5%). Bcl-2 aberration tended to have an adverse effect on survival. In multivariate analysis, MYC ICN was an independent poor prognostic factor.
Analyses of MYC and Bcl-2 status, i.e. translocation and ICN, in the context of DLBCL phenotype might help predict prognosis and determine therapeutic strategies.
Histopathology 09/2008; 53(2):205-17. · 3.08 Impact Factor
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T M Kim,
S-Y Lee, Y K Jeon,
B-Y Ryoo,
G J Cho,
Y S Hong,
H J Kim,
S-Y Kim,
C S Kim,
S Kim,
J S Kim,
S K Sohn,
H H Song,
J L Lee,
Y K Kang,
C Y Yim,
W S Lee,
Y J Yuh,
C W Kim,
D S Heo
[show abstract]
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ABSTRACT: This national survey was undertaken to propose the classification of extranodal natural killer (NK)/T-cell lymphoma (NTCL) subtypes and to clarify a clinical heterogeneity.
Two hundred and eighty patients newly diagnosed as NTCL were enrolled from 22 Korean medical centers. Two subsets were compared: one involving the upper aerodigestive tract (UAT) and another involving the non-upper aerodigestive tract (NUAT) region, which comprises the skin, gastrointestinal tract, and liver or soft tissues. Clinical prognostic factors, survival outcomes, and independent predictors for survival were compared between each subset.
NUAT-NTCL (59 patients) had significantly higher proportions of disseminated disease, aggressive biologic features, and unfavorable host reactions compared with UAT-NTCL (221 patients). NUAT-NTCL had shortened 5-year overall survival (OS) (22% versus 41%, P = 0.001). Ann Arbor staging, the International Prognostic Index, and the NTCL prognostic index failed to predict the OS of NUAT-NTCL, but did predict the OS in UAT-NTCL. Independent predictors for OS by multivariate analyses differed between each subset. In the NUAT subset, extranodal sites and regional nodes predicted the OS, while Ann Arbor staging, age, performance status, and lactate dehydrogenase level predicted the OS in the UAT subset.
NUAT-NTCL may represent a distinctive disease entity in terms of clinical factors, independent predictors, and survival outcomes.
Annals of Oncology 05/2008; 19(8):1477-84. · 6.43 Impact Factor
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ABSTRACT: Epidermal growth factor receptor (EGFR) expression has been observed in a variety of solid tumours with the potential of new targeted therapeutic agents. The aim was to evaluate the EGFR status of gastric carcinoma (GC) using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH).
The EGFR status was evaluated in GC tissues from 511 patients using IHC and FISH. In addition, the clinicopathological characteristics were examined and the results were compared with the EGFR status. One hundred and forty cases (27.4%) showed EGFR overexpression by IHC. EGFR overexpression was associated with older age (P = 0.001), moderately or poorly differentiated histology (P = 0.001) and higher stage disease (P = 0.046). Sixteen cases (3.1%) showed high polysomy and 12 cases (2.3%) had gene amplification by FISH. The correlation between IHC and FISH results was statistically significant (P < 0.001). The patients with GC who had EGFR overexpression had an unfavourable prognosis and multivariate analysis showed that EGFR overexpression was a possible independent unfavourable prognostic factor.
EGFR overexpression was observed in a subset of cases with GC and was associated with an unfavourable prognosis. It will be important to evaluate EGFR status to interpret future clinical trials properly using EGFR targeted agents.
Histopathology 05/2008; 52(6):738-46. · 3.08 Impact Factor
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D-W Kim,
H S Min,
K-H Lee,
Y J Kim,
D-Y Oh, Y K Jeon,
S-H Lee,
S-A Im,
D H Chung,
Y T Kim,
T-Y Kim,
Y-J Bang,
S W Sung,
J H Kim,
D S Heo
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ABSTRACT: The purpose of this study was to investigate the prognostic value of tumour-associated macrophages with a focus on micro-anatomical localisation and determine whether molecular changes of the epidermal growth factor receptor (EGFR) are related to macrophage infiltration in resected non-small cell lung cancer (NSCLC). One hundred and forty-four patients were included in this study. Immunohistochemistry was used to identify CD68+ macrophages in the tumour islet and surrounding stroma. Epidermal growth factor receptor mutations were studied by direct sequencing. The EGFR gene copy number and protein expression were analysed by fluorescence in situ hybridisation and immunohistochemistry. Patients with a high tumour islet macrophage density survived longer than did the patient with a low tumour islet macrophage density (5-year overall survival rate was 63.9 vs 38.9%, P=0.0002). A multivariate Cox proportional hazard analysis revealed that the tumour islet macrophage count was an independent prognostic factor for survival (hazard ratio 0.471, 95% confidence interval 0.300-0.740). However, EGFR mutations, gene copy number, and protein expression were not related to the macrophage infiltration. In conclusion, tumour islet macrophage infiltration was identified as a strong favourable independent prognostic marker for survival but not correlated with the molecular changes of the EGFR in patients with resected NSCLC.
British Journal of Cancer 04/2008; 98(6):1118-24. · 5.04 Impact Factor
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ABSTRACT: Background. To evaluate the prognostic value of the expressions of epidermal growth factor receptor (EGFR) and cyclin D1 in early glottic cancer treated with radiotherapy only. Methods. One hundred fifty-one patients with T1-2, N0 glottic cancer who had been treated with radiotherapy at Seoul National University Hospital since 1992 through 2004. Immuno-histochemical staining for EGFR and cyclin D1 were performed on the formalin-fixed paraffin-embedded tissues of 25 patients who developed local recurrence and on the tissues of 25 matched patients free from disease. Patterns and degrees of expression were compared between these 2 groups. Results. High EGFR (p = .047) and high cyclin D1 (p = .040) expressions were both found to be significantly associated with a poor prognosis. No association was found between EGFR and cyclin D1 status (p = .158), but EGFR and cyclin D1 status in combination were found to be significantly associated with local control. The patients with both high EGFR and high cyclin D1 expression had the poorest outcome compared with the others (14 months vs 29 months of median time to progression). Patterns of EGFR and cyclin D1 expression changed after recurrence, but these changes were not found to alter the ultimate prognosis. Conclusion. The molecular biomarkers, EGFR and cyclin D1 have a prognostic significance in early glottic cancer. These markers in combination seem to play an important role in tumor relapse and may be useful for selecting patients with a poor outcome after radiotherapy. ©2008 Wiley Periodicals, Inc.
Head and Neck. 01/2008; 30(7):852-857.
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ABSTRACT: NK/T-cell lymphoma (NKTL) is strongly associated with latent Epstein-Barr virus (EBV) infection. Recently, latent membrane protein 1 (LMP1), an EBV oncoprotein, was reported to activate the phosphatidylinositol-3 kinase (PI3K)/Akt pathway for cell survival. Because geldanamycin (GA) and its derivative, 17-allylamino-17-demethoxygeldanamycin (17-AAG), exhibit anti-tumour activity by degrading HSP90 client proteins, including Akt, we investigated the effect of GA and 17-AAG on the survival of NKTL cell lines. EBV-positive NKTL cell lines, Hank-1 and NK-YS, and an EBV-negative NK leukaemia cell line, NK-L, were treated with PI3K and Akt inhibitors, GA, and 17-AAG, and were subjected to apoptosis and cell viability assays, and immunoblot analysis. EBV-positive B-lymphoblastoid cell lines IM9 and LMP1-transfected IM9 (IM9-LMP1) were also included. Hank-1 and NK-YS cell viability was compromised and apoptosis was induced by LY294002 (PI3K inhibitor) or Akt inhibitor II. GA or 17-AAG administration resulted in the apoptosis of NKTL cells, accompanied by Akt and pAkt down-regulation, caspase 3 activation, and mitochondrial membrane potential disruption. The intrinsic level of pAkt was higher in EBV-positive NKTL cells than in EBV-negative NK-L, and GA or 17-AAG decreased the viability of NKTL cells more efficiently than NK-L. Moreover, IM9-LMP1 was more sensitive to Akt inhibitor II or HSP90 inhibitors than IM9. Importantly, GA showed little effect on the viability of normal peripheral NK cells as non-neoplastic counterparts for comparison. In conclusion, this study suggests that the PI3K/Akt pathway is frequently activated in EBV-positive NKTL and that therapeutic modalities based on targeting the PI3K/Akt pathway with HSP90 inhibitors could be useful for achieving NKTL control.
The Journal of Pathology 11/2007; 213(2):170-9. · 6.32 Impact Factor
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ABSTRACT: To evaluate the different expression patterns and the prognostic significance of cell cycle regulatory molecules in diffuse large B-cell lymphomas (DLBCLs) of germinal centre (GC) and non-GC phenotypes.
Tissue microarray slides composed of 126 extranodal and 88 nodal DLBCLs were immunostained for p16, p21, p27, p14 and p53. DLBCLs were classified into GC and non-GC phenotype according to the immunohistochemical expression of bcl-6, CD10, and MUM1. Aberrant expression of p53 was more frequent in the GC phenotype in nodal cases (P = 0.038), and the loss of p16, p21 and p14 expression was significantly more common in the non-GC phenotype (P = 0.004, P = 0.001, P < 0.001). Concurrent disruptions of the p16-Rb and p14-p53 pathways as represented by the immunoprofile of p16/p14/p53 (-/-/+) were associated with a poor prognosis in the GC phenotype [mean survival 31 months in the p16/p14/p53 (-/-/+) group versus 62 months in the other groups, P =0.0485].
The expression and prognostic implications of cell cycle regulatory molecules differ between GC and non-GC phenotypes in DLBCLs. The immunoprofile of p16/p14/p53 (-/-/+) within the GC phenotype of DLBCLs can be defined as a poor prognostic subgroup.
Histopathology 09/2005; 47(3):281-91. · 3.08 Impact Factor
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ABSTRACT: Adult onset Still's disease (AOSD) is a rare systemic inflammatory disorder of unknown aetiology, frequently accompanying multiple lymphadenopathy. It often mimics malignant lymphoma, and immunohistochemical and molecular studies are needed for definite diagnosis.
To aid in diagnosis and understand the pathogenesis of the disease by clarifying lymph node (LN) pathology in AOSD.
Thirteen biopsies (one follow up biopsy) and medical records of 12 patients were reviewed. Immunohistochemistry, polymerase chain reaction for T cell receptor gamma chain (TCRgamma) and immunoglobulin heavy chain gene rearrangement, and Epstein-Barr virus in situ hybridisation were performed.
Histologically, LN lesions were classified into four patterns. The most common (six biopsies) showed paracortical hyperplasia, with prominent vascular proliferation, scattered large B/T immunoblasts, and infiltration by reactive lymphocytes and inflammatory cells. In the second pattern (two biopsies), paracortical hyperplasia was accompanied by massive sinus histiocytosis and S-100 positive histiocyte aggregates. The third pattern (three patients) showed an exuberant immunoblastic reaction, in the form of patchy/diffuse infiltration of large T immunoblasts with high mitotic activity, although clonal rearrangement of the TCRgamma gene was not detected. The fourth pattern showed distinct follicular hyperplasia (two cases). One patient with a follow up biopsy showed a pattern change from pronounced follicular hyperplasia to atypical paracortical hyperplasia.
AOSD LN lesions show a dynamic histological spectrum, including atypical paracortical hyperplasia, burnt out histiocytic reaction, exuberant immunoblastic reaction, and follicular hyperplasia. During the course of disease, LN reactivity changes and mixed B and T cells are involved in the pathogenesis.
Journal of Clinical Pathology 11/2004; 57(10):1052-6. · 2.31 Impact Factor
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K-H Cho,
S-H Lee,
C-W Kim, Y-K Jeon,
I-H Kwon,
Y-J Cho,
S-K Lee,
D-H Suh,
J-H Chung,
T-Y Yoon,
S-J Lee
[show abstract]
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ABSTRACT: There are many reports of patients with a severe hydroa vacciniforme (HV)-like eruption in which cutaneous lesions occur in both sun-exposed and non-exposed areas, unlike in true HV. Several patients have died from a malignant haematological neoplasm. In most cases, a latent Epstein-Barr virus (EBV) infection has been detected in the skin lesions.
To describe the clinical and laboratory features of six additional patients with an EBV-associated HV-like eruption.
The clinical, histological and immunohistochemical features were reviewed. T-cell receptor gamma gene rearrangements were studied using polymerase chain reaction (PCR) and heteroduplex analysis. In-situ hybridization was performed to detect mRNA for EBV in skin biopsy specimens. PCR was performed to screen for EBV infection in the skin lesions of three patients and blood of two patients. Photoprovocation with repeated ultraviolet (UV) A exposure was performed in three patients.
The severity of the skin lesions and the clinical course varied among the patients. Skin lesions were induced by repeated UVA exposure in three patients and a latent EBV infection was demonstrated in the photoprovoked lesions.
Three different clinical courses were found in six patients with an HV-like eruption associated with chronic EBV infection: (i) spontaneous remission; (ii) clearing after photoprotection; and (iii) continuous recurrence irrespective of sun exposure. It is possible that there are two patterns of HV-like eruption associated with chronic EBV infection. One is characterized by recurrent necrotic papulovesicles of the face and the other by nodules and facial swelling. It was demonstrated that the skin lesions could be triggered by repeated UVA exposure in the patients showing recurrent necrotic papulovesicles of the face.
British Journal of Dermatology 09/2004; 151(2):372-80. · 3.67 Impact Factor
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ABSTRACT: The morphology of calretinin- and tyrosine hydroxylase-immunoreactive (IR) neurons in adult pig retina was studied. These neurons were identified using antibody immunocytochemistry. Calretinin immunoreactivity was found in numerous cell bodies in the ganglion cell layer. Large ganglion cells, however, were not labeled. In the inner nuclear layer, the regular distribution of calretinin-IR neurons, the inner marginal location of their cell bodies in the inner nuclear layer, and the distinctive bilaminar morphologies of their dendritic arbors in the inner plexiform layer suggested that these calretinin-IR cells were AII amacrine cells. Calretinin immunoreactivity was observed in both A-and B-type horizontal cells. Neurons in the photoreceptor cell layer were not labeled by this antibody. The great majority of tyrosine hydroxylase-IR neurons were located at the innermost border of the inner nuclear layer (conventional amacrines). The processes were monostratified and ran laterally within layer 1 of the inner plexiform layer. Some of the tyrosine hydroxylase-IR neurons were located in the ganglion cell layer (displaced amacrines). The processes of displaced tyrosine hydroxylase-IR amacrine cells were also located within layer 1 of the inner plexiform layer. Some processes of a few neurons were located in the outer plexiform layer. A very low density of neurons had additional bands of tyrosine hydroxylase-IR processes in the middle and deep layers of the inner plexiform layer. The processes of tyrosine hydroxylase-IR neurons extended radially over a wide area and formed large, moderately branched dendritic fields. These processes occasionally had varicosities and formed "dendritic rings". These results indicate that calretinin- and tyrosine hydroxylase-IR neurons represent specific neuronal cell types in the pig retina.
Molecules and Cells 05/2001; 11(2):250-6. · 2.18 Impact Factor
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T M Kim,
S Y Lee, Y K Jeon,
B Y Ryoo,
G J Cho,
Y S Hong,
H J Kim,
S Y Kim,
C S Kim,
S Kim, [......],
S K Sohn,
H H Song,
J L Lee,
Y K Kang,
C Y Yim,
W S Lee,
Y J Yuh,
C W Kim,
D S Heo,
for the Lymphoma Subcommittee of the Korean Cancer Study Group
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ABSTRACT: Background: This national survey was undertaken to propose the classification of extranodal natural killer (NK)/T-cell lymphoma (NTCL) subtypes and to clarify a clinical heterogeneity. Patients and methods: Two hundred and eighty patients newly diagnosed as NTCL were enrolled from 22 Korean medical centers. Two subsets were compared: one involving the upper aerodigestive tract (UAT) and another involving the non-upper aerodigestive tract (NUAT) region, which comprises the skin, gastrointestinal tract, and liver or soft tissues. Clinical prognostic factors, survival outcomes, and independent predictors for survival were compared between each subset. Results: NUAT-NTCL (59 patients) had significantly higher proportions of disseminated disease, aggressive biologic features, and unfavorable host reactions compared with UAT-NTCL (221 patients). NUAT-NTCL had shortened 5-year overall survival (OS) (22% versus 41%, P = 0.001). Ann Arbor staging, the International Prognostic Index, and the NTCL prognostic index failed to predict the OS of NUAT-NTCL, but did predict the OS in UAT-NTCL. Independent predictors for OS by multivariate analyses differed between each subset. In the NUAT subset, extranodal sites and regional nodes predicted the OS, while Ann Arbor staging, age, performance status, and lactate dehydrogenase level predicted the OS in the UAT subset. Conclusion: NUAT-NTCL may represent a distinctive disease entity in terms of clinical factors, independent predictors, and survival outcomes.
