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ABSTRACT: Podoplanin, a type-1 transmembrane glycoprotein, was originally named due to its expression in renal podocytes of rats. It was subsequently detected in a variety of normal human tissues, including lymphatic endothelium. Although podoplanin has been identified as the endogenous ligand of C-type lectin-like receptor 2 (CLEC-2) on platelets, its physiological functions and pathways remain largely unknown. A role in lymphangiogenesis has been suggested, since podoplanin-deficient mice were found to die at birth with a phenotype of dilated, malfunctioning lymphatic vessels and lymphedema. Podoplanin is invariably expressed in some tumors, such as lymphangioma, seminoma and follicular dendritic cell tumor, but tumor cell expression of podoplanin is highly variable in squamous cell carcinoma (SCC). It has been found that high podoplanin expression is associated with lymph node metastasis and poor prognosis in SCC of the upper aerodigestive tract. Now there is growing evidence that podoplanin is also involved in carcinogenesis, cell motility, tumor invasiveness, platelet aggregation and hematogenous metastasis. Additionally, animal studies confirmed some in vivo effects of podoplanin-overexpressing tumors, including formation of more tumor lymphatic vessels, larger lymph node metastases, more platelet aggregation, and more pulmonary metastases. Several recently developed anti-podoplanin antibodies, such as NZ-1, P2-0 and hP2-0, have been shown to attenuate podoplanin-induced platelet aggregation and prevent experimental hematogenous metastasis in nude mice. These antibodies may be applied in preclinical and clinical studies to evaluate the possibility of podoplanin-targeted therapy.
Histology and histopathology 03/2013; 28(3):293-9. · 2.48 Impact Factor
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ABSTRACT: Heterogeneous nuclear ribonucleoprotein K (hnRNP K) mediates antiapoptotic activity in part by inducing downstream antiapoptotic genes. To systematically identify hnRNP K targets in nasopharyngeal carcinoma (NPC), affymetrix chips were used to identify genes that were both overexpressed in primary NPC and downregulated by hnRNP K knockdown in NPC-TW02 cells. The resulting gene set included the antiapoptotic gene, FLIP, which was selected for further study. In cells treated with hnRNP K siRNA, TRAIL-induced apoptosis was enhanced and the FLIP protein level was reduced. Promoter, DNA pull-down and chromatin-immunoprecipitation assays revealed that hnRNP K directly interacts with the poly(C) element on the FLIP promoter, resulting in transcriptional activation. Through iTRAQ-mass spectrometric identification of proteins differentially associated with the poly(C) element or its mutant, nucleolin was determined to be a cofactor of hnRNP K for FLIP activation. Furthermore, FLIP was highly expressed in tumor cells, and this high-level expression was significantly correlated with high-level hnRNP K expression (P=0.002) and poor overall survival (P=0.015) as examined in 67 NPC tissues. A multivariate analysis confirmed that FLIP was an independent prognostic factor for NPC. Taken together, these findings indicate that FLIP expression is transcriptionally regulated by hnRNP K and nucleolin, and may be a potential prognostic and therapeutic marker for NPC.
Cell death and differentiation 03/2010; 17(9):1463-73. · 8.24 Impact Factor
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ABSTRACT: The cytoplasmic level of heterogeneous nuclear ribonucleoprotein K (hnRNP K) is significantly correlated with the elevated expression of thymidine phosphorylase (TP), and high levels of both proteins are predictive of a poor prognosis in nasopharyngeal carcinoma (NPC). We herein show that TP is highly induced by serum deprivation in NPC cells, and that this is due to an increase in the half-life of the TP mRNA, as shown by nuclear run-on and actinomycin D assays. We further show that the CU-rich element of the TP mRNA directly interacts with hnRNP K, as demonstrated by immunoprecipitation RT-PCR assays, and the nucleus-to-cytoplasm translocation of hnRNP K. Blockade of hnRNP K expression reduces TP expression, suggesting that hnRNP K acts in the upregulation of TP. Mechanistically, both MEK inhibitor and the hnRNP K ERK-phosphoacceptor-site mutant decrease cytoplasmic accumulation of hnRNP K, suggesting that ERK-dependent phosphorylation is critical for TP induction. Furthermore, we found that hnRNP K-mediated TP induction allows NPC cells to resist hypoxia-induced apoptosis. Our results collectively establish the regulation and role of ERK-mediated cytoplasmic accumulation of hnRNP K as an upstream modulator of TP, suggesting that hnRNP K may be an attractive candidate as a future therapeutic target for cancer.
Oncogene 04/2009; 28(17):1904-15. · 6.37 Impact Factor
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ABSTRACT: Apoptosis, or programmed cell death, is now recognised as an important cellular event during both normal development and specific disease progression. Apoptosis has been suggested to play a critical role in several cardiovascular diseases, but has not yet been identified as a major influence in primary cardiac tumours. A retrospective review of the achieved material at Chang Gung Memorial Hospital revealed seven patients with cardiac myxoma and one with a tumour originating from the crista terminalis, from January 2002 to December 2002. The medical chart, surgical pathology reports and microscopic slides were available in all cases. All patients, including eight cardiac myxomas and one tumour from crista terminalis, were assessed for apoptosis by terminal deoxynucleotidyl transferase nick-end labelling assay. In this study, apoptosis is well documented in all seven myxoma and has even been reported in tumour from the crista terminalis. Interestingly, apoptosis appears related to the nature of the cell properties rather than the incidence of embolism. In conclusion, apoptosis is important in the progression of the primary cardiac tumours, but the mechanism of cardiac tumour regression still remains uncertain.
International Journal of Clinical Practice 07/2004; 58(6):564-7. · 2.41 Impact Factor
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Transplantation Proceedings 09/2002; 34(5):1462. · 1.00 Impact Factor
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ABSTRACT: To determine the role of ultrasound (US)-guided core needle biopsy as an initial diagnostic test for palpable breast masses.
Ninety-eight consecutive patients, each with a palpable breast mass, were referred for US-guided core biopsy by a multidisciplinary team of physicians who specialize in the care of breast diseases. All palpable breast masses were clearly visible on high-resolution US. Ninety-nine core needle biopsies were performed under local anesthesia with use of freehand technique, mostly in an outpatient setting. Core needle path through each mass was documented in two orthogonal sections. A mean of 3.4 tissue core samples (range, 1-7) were obtained in each patient.
Core needle biopsy resulted in the diagnosis of 66 malignancies, two cases of atypical ductal hyperplasia (ADH), and 30 benign diseases of the breast. Surgery with curative intent was performed in 63 breast malignancies and excisional biopsies were performed for 10 benign diseases (two cases of ADH and eight benign lesions). Twenty-five breast masses were managed nonoperatively: chemotherapy was performed in three locally advanced breast cancers and 3-year follow-up was conducted for 22 benign lesions. Malignancies were correctly diagnosed in all cases. No malignancy was discovered at surgery or during clinical follow-up of ADH and no benign breast lesions were diagnosed by core needle biopsy. US-guided core needle biopsy is 100% sensitive and specific for palpable breast malignancies, with no false-positive results. A puncture site ecchymosis was the only morbidity or complication noted.
US-guided core needle biopsy is a safe and accurate first diagnostic test for palpable breast masses that require tissue proof.
Journal of Vascular and Interventional Radiology 12/2001; 12(11):1313-7. · 2.08 Impact Factor
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ABSTRACT: Hamartoma in the nasal cavity of children is especially rare. Most documented cases occurred in infants, with characteristic histologic features of a mixture of various mesenchymal tissues. McDermott et al designated it nasal chondromesenchymal hamartoma in 1998, and it has since been considered a distinct clinicopathological entity. We report 2 such examples in a full-term male newborn and a 9-month-old boy, respectively. Histologically, both cases were characterized by a mixture of various mesenchymal elements, including spindle cells, collagen fibers, and irregular islands of osseous and chondroid tissue. Immunohistochemical study showed positivity to vimentin and S100 protein. Ultrastructural examination of case 1 demonstrated fibroblastic and myofibroblastic differentiation in tumor cells. There were 11 cases of nasal chondromesenchymal hamartoma in children published to date. The tumor has a benign biological behavior, and complete resection is the treatment of choice. It is apt to be misdiagnosed because of overlapping histologic features shared with a number of benign and malignant soft tissue tumors. Awareness of this entity is essential for correct diagnosis and adequate therapy.
Archives of pathology & laboratory medicine 04/2001; 125(3):400-3. · 2.58 Impact Factor
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ABSTRACT: Langerhans cell histiocytosis (LCH) is an enigmatic disease usually occurring in children. Tumor lysis syndrome (TLS) is a clinical syndrome associated with severe metabolic derangement and oliguric acute renal failure. In this report, we present the clinical course of an infant with advanced LCH who had TLS develop after chemotherapy. Treatment with continuous arteriovenous hemofiltration resulted in effective control of serum uric acid, potassium, creatinine, phosphorus, and blood urea nitrogen levels in the blood.
Journal of Pediatric Hematology/Oncology 03/2001; 23(2):142-4. · 1.16 Impact Factor
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ABSTRACT: The extent of human sodium iodide symporter (hNIS) expression in different kinds of human thyroid cancer tissues and cell lines remains controversial. In this study, polyclonal antibodies to hNIS were used to analyze the expression of symporter protein in benign and malignant human thyroid tissues. Formalin-fixed, paraffin wax-embedded tissue sections were used. Staining was performed using primary polyclonal antibody of rabbit anti-human hNIS diluted in PBS (1:500). Results showed that 2 of 3 normal tissue, 3 of 6 nodular hyperplasia, one follicular adenoma, 3 of 11 papillary thyroid carcinoma, 1 of 5 follicular carcinoma and none of 3 metastatic thyroid epithelial tissue specimens stained positively for hNIS. A higher percentage of positive staining for symporter protein was found in benign thyroid tissues including normal thyroid tissue, nodular hyperplasia, and adenoma (60%). In contrast, papillary and follicular thyroid carcinomas demonstrated lower symporter protein expression (20%). In conclusion, although the number of tissue samples examined in this study was small, hNIS staining found a higher ratio of symporter protein expression in normal and benign thyroid tissues compared with malignant tissues. Determination of the reason for discrepancies in the expression of hNIS in in vivo and in vitro studies will require further investigation.
Endocrine Pathology 02/2001; 12(1):15-21. · 1.36 Impact Factor
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ABSTRACT: Patients with follicular thyroid carcinoma have a higher incidence of metastasis than papillary thyroid carcinoma when thyroid cancer is diagnosed. The cDNA expression array technology is utilized herein to profile differentially expressed genes from metastatic human follicular thyroid carcinoma and reveal new tumor markers as well as target genes for therapeutic intervention. Tissue samples were obtained during surgical resection of the thyroid follicular carcinoma and metastatic tissue in the brain of the same patient. Two identical Atlas human cDNA expression arrays were hybridized with 32P-labeled cDNA probes derived from RNA of either primary thyroid cancer or metastatic tissue. Parallel analysis of the hybridized signals allowed us to identify the alteration of gene expression in the metastasis process. Eighteen genes significantly overexpressed and 40 genes significantly underexpressed were identified in the metastatic thyroid cancer. Genes that displayed an altered expression were associated with the processes of cell cycle regulation, apoptosis, DNA damage response, angiogenesis, cell adhesion and mobility, invasion, and immune response. An expression profile of genes that are associated with metastasis process of follicular thyroid cancer was also discussed. Further investigation is required to understand the precise relationship between the altered expression of these genes and the metastasis process of follicular thyroid cancer.
Thyroid 02/2001; 11(1):41-6. · 4.79 Impact Factor
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ABSTRACT: We evaluated the value of ultrasound-guided needle biopsy in 20 soft tissues masses about superficial bone lesions in 20 oncology patients. Sonographically guided needle biopsies were performed without an on-site pathologist. A diagnostic sensitivity of 95% and specificity of 100% in separating a benign or a malignant lesion was obtained. Fine needle aspiration cytology allowed the specific cell type of malignancy to be diagnosed in 80% of cases, while core needle biopsy allowed it in 91%. Real-time ultrasonographic guidance permits precise needle placement into the targets, avoidance of hypervascular areas, and flexibility of patient positioning so that needle biopsy can be performed quickly and safely on soft tissue masses about superficial bone lesions.
Journal of ultrasound in medicine: official journal of the American Institute of Ultrasound in Medicine 01/2001; 19(12):849-55. · 1.25 Impact Factor
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The Journal of otolaryngology 09/2000; 29(4):257-9. · 0.50 Impact Factor
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S R Shih,
M S Ho,
K H Lin,
S L Wu,
Y T Chen,
C N Wu,
T Y Lin,
L Y Chang,
K C Tsao,
H C Ning,
P Y Chang,
S M Jung, C Hsueh,
K S Chang
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ABSTRACT: A large scale outbreak of hand-foot-and-mouth disease (HFMD) occurred in Taiwan in 1998, in which more than 80 children died of shock syndrome with pulmonary edema/hemorrhage. Enterovirus 71 was implicated as the cause of this outbreak. In order to understand the virological basis responsible for mortality on this scale, nucleotide sequences of VP1 that is important for serotypic specificity, and the 5'-non-coding region (5'-NCR) that is important for replication efficiency, were analyzed comparatively. Phylogenetic analysis of both VP1 and 5'-NCR of nine EV71 isolates derived from specimens of fatal patients and seven isolates derived from uncomplicated HFMD patients showed that all but one isolate fell into genotype B. The one distinct isolate from a case of uncomplicated HFMD belonged to genotype C that was clustered along with one isolate from Taiwan in 1986. Complete sequence analysis of two selected isolates, one from the spinal cord of a fatal case and one from the vesicle fluid of a patient with mild HFMD, confirmed a high degree (97-100%) of identity in nucleotide sequence throughout the entire genome, except focal regions of 3C and 3'-NCR where the nucleotide homology was 90-91%. The identity of the deduced amino acid sequence in the 3C region that encodes viral proteinase dropped further to 86%, a result of missense mutations at the first nucleotide position of many codons.
Virus Research 08/2000; 68(2):127-36. · 2.94 Impact Factor
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ABSTRACT: Active iodide uptake across the basal membrane mediated by human sodium iodide symporter (hNIS) has been shown to be a process coupled with the flow of sodium. There is still controversy as to the amount of hNIS expression present in different kinds of human thyroid cancer tissues. In this study, we present a 58-year-old women with follicular thyroid carcinoma with vertebra and skull metastases. 201Tl and 5 mCi 131I scans clearly demonstrated the metastatic lesions in the brain of this patient. Thyroid and metastatic tissues were then obtained for this study, which is aimed at comparing the iodide trapping ability in vivo and in vitro of hNIS, and then comparing their expression in both thyroid tissue and metastatic tissues. Polyclonal antibodies to hNIS and competitive RT PCR were used to analyze the symporter protein and mRNA expressed in follicular human thyroid and metastatic tissues. Positive staining of the symporter protein was performed in the follicular thyroid carcinomas, otherwise, the metastatic tissues could not have demonstrated the protein in the staining. Follicular thyroid carcinoma tissues from thyroid were revealed around 5 pg hNIS expressed in follicular thyroid carcinoma tissues from the thyroid. Otherwise, there was almost an absence of hNIS expression in the metastatic tissue. These discrepancies of the expression in hNIS in vivo and in vitro studies need further investigation.
Annals of Oncology 06/2000; 11(5):625-9. · 6.43 Impact Factor
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ABSTRACT: Screening programs using urinary vanillylmandelic acid have detected neuroblastomas in early infancy with some success. With the widespread use of ultrasonography in modern obstetric practice, use of ultrasonography to screen for fetal neuroblastoma seems to be reasonable and practical.
Seven fetuses had suprarenal masses detected by maternal ultrasound scan at 32 to 37 weeks' gestation between 1993 and 1998. They were delivered normally if the pregnancy was uncomplicated, especially if it was without maternal preeclampsia or fetal hydrops. Each mass was further confirmed by ultrasound scan, computed tomography, or magnetic resonance imaging in the neonatal period. Tumor excision was performed at the age of 6 to 38 days of life.
The size of the masses measured ranged from 2.0x2.0 cm to 4.5x4.5 cm. The diagnosis was adrenal hemorrhage in 1 neonate, Evan's stage I neuroblastoma in 3, and stage IV-S neuroblastoma in 3. All of the specimens with a diagnosis of neuroblastoma showed a favorable histology by the Shimada classification system. Infants with stage I disease were treated with tumor excision only, and they had survived without disease by 14, 18, and 25 months of follow-up. One infant with stage IV-S neuroblastoma was treated further with minimal chemotherapy and has survived without disease at the 66-month follow-up examination. Another child with stage IV-S neuroblastoma has survived with local recurrence and increasing liver metastasis and was still on chemotherapy at the 2-month follow-up examination. The third child with stage IV-S disease presented with massive hepatomegaly and bone marrow involvement, and disseminated intravascular coagulopathy had developed. The patient died on the 5th day of life without surgical intervention.
The increasing use of obstetric ultrasonography has made the prenatal screening of neuroblastomas possible. The prognosis of infants with a suprarenal mass may be improved with this early detection and early surgical intervention.
Journal of Pediatric Surgery 12/1999; 34(11):1620-3. · 1.45 Impact Factor
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L Y Chang,
T Y Lin,
K H Hsu,
Y C Huang,
K L Lin, C Hsueh,
S R Shih,
H C Ning,
M S Hwang,
H S Wang,
C Y Lee
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ABSTRACT: In Taiwan, from April to July, 1998, an epidemic of hand, foot, and mouth disease associated with enterovirus 71 (EV71) occurred with fatal complications. We did a clinical study of EV71-related diseases in Taiwan.
We studied 154 children with virus-culture confirmed EV71 infection. Children were divided into three groups: 11 patients with pulmonary oedema; 38 patients with central nervous system (CNS) involvement and no pulmonary oedema; and 105 children without complications. We compared the clinical features, laboratory findings, risk factors, and outcome among these three groups.
Nine children with pulmonary oedema had hand, foot, and mouth disease, one had herpangina, and one had febrile illness with eight children with limb weakness and one with limb hypesthesia. All children had had sudden onset of tachycardia, tachypnoea, and cyanosis 1-3 days after onset of the disease. Nine of 11 children died within 12 h of intubation; one child was braindead within 15 h and died 17 days after intubation; one child was in deep coma and died 3 months later. In children with CNS complication and no pulmonary oedema, one child died of pneumonia after 4 months of ventilator support and four children had sequelae. All 105 children without complications recovered. There was a significant association between CNS involvement and pulmonary oedema (odds ratio 12.4 [95% CI 2.6-60.1], p=0.001). Risk factors for pulmonary oedema after CNS involvement were hyperglycaemia, leucocytosis, and limb weakness. Hyperglycaemia was the most significant prognostic factor for pulmonary oedema (odds ratio 21.5 [3-159], p=0.003).
EV71 can cause hand, foot, and mouth disease, CNS involvement with severe sequelae, and fatal pulmonary oedema. Hyperglycaemia is the most important prognostic factor.
The Lancet 12/1999; 354(9191):1682-6. · 38.28 Impact Factor
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ABSTRACT: Controversies still exist around the diagnosis and management of Hürthle cell tumors. The aim of this study is to reexamine our experience to improve our methods in the future.
We treated 34 patients with verified Hürthle cell carcinoma and adenoma at Chang Gung Memorial Hospital, Linkou from 1990 through 1996. Clinical characteristics, thyroid ultrasonogram, 131I, 201Tl, 99mTc-methoxy-isobutyl-isonitrile (MIBI) and 99mTc-thyroid scan, fine needle aspiration cytology (FNAC) and histology results were analyzed.
Female predominance (82.4%) was noticed among our Hürthle cell tumors. Nine (26.5%) patients had carcinoma. The median size of carcinoma was 4.0 cm, which was significantly larger than the median 3.0 cm for adenoma. No significant differences were found between gender, age, multiplicity or echogenicity between two groups. All 12 adenoma and 3 carcinoma patients who received pre-operative 99mTc and/or 131I thyroid scan showed cold nodules. The sensitivity and specificity of detection Hürthle cell carcinoma as indeterminate and malignant using FNAC was 78% and 18% respectively. These improved to 100% and 86% using frozen sections. One carcinoma patient developed neck lymph node metastasis, with normal serum thyroglobulin, negative 131I but positive 201Tl and 99mTc-MIBI whole body scans. Another one showed mediastinum metastasis with elevated serum thyroglobulin, detected using 131I scan, revealed successful regression after 131I therapeutic scan.
Tumor size of carcinoma is significantly larger than adenoma. All patients with FNAC suggestive of Hürthle cell tumors should receive surgery for histological diagnosis to differentiate carcinoma from adenoma. Therapeutic radioiodine ablation is indicated whenever there is 131I uptake by tumor cells.
Changgeng yi xue za zhi / Changgeng ji nian yi yuan = Chang Gung medical journal / Chang Gung Memorial Hospital. 10/1999; 22(3):445-52.
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ABSTRACT: The incidence of a normal live fetus and a partial molar placenta is extremely rare. Although triploidy is the most frequent association, a fetus with normal karyotype can survive in cases of partial molar pregnancy. We report a case of partial molar placenta in which a live female baby was delivered at 32 weeks gestation by a 30-year-old woman. At the 18th week, ultrasonographic examination revealed a normal fetus with a huge, multicystic placenta. Chromosomal evaluation by amniocentesis revealed a normal female karyotype (46,XX), and serial biometric measurement of the fetus showed normal growth during pregnancy. There were no obstetric complications until the 32nd gestational week when preterm rupture of the membranes occurred. The electronic fetal heart beat tracing showed a repeated sinusoid pattern and late deceleration after admission. The patient underwent emergency Caesarean section and delivered a 1551-g, anaemic female baby with an Apgar score of 1, 4 and 6 at 1, 5 and 10 min, respectively. The baby recovered within 2 weeks after respiratory support and transfusion of packed red blood cells. Although anaemia is one of the risk factors that jeopardize the fetus in the case of partial molar pregnancy, termination is not indicated when the fetus is normal and no complications have occurred.
Human Reproduction 05/1999; 14(4):1122-6. · 4.47 Impact Factor
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ABSTRACT: A previously healthy 18-year-old boy presented with daily spiking fever, polyarthritis, and evanescent skin rashes, as well as hepatomegaly and Raynaud's phenomena for 2 months. He was initially diagnosed with adult-onset Still's disease (AOSD). During the period of follow-up, intermittent fever and migratory polyarthritis persisted and an insidiously growing mass over the right axillary region was noted 1 year after the diagnosis of AOSD. Excisional biopsy of the mass revealed a group of lymph nodes with histological features of the hyaline vascular type of Castleman's disease. The patient's symptoms disappeared soon after excision of the lymph nodes. evanescent rash, lymphadenopathy, hepatosplenomegaly and serositis [5]. A clinical picture compatible with the diagnosis of AOSD has not been described in the localised hyaline vascular type of Castleman's disease. We report such a case in an 18-year-old male patient who presented prolonged fever and polyarthritis with an initial diagnosis of AOSD. The diagnosis of hyaline vascular type of Castleman's disease was made 1 year later, when the patient developed an insidiously growing mass over the right axilla.
Clinical Rheumatology 02/1999; 18(6):485-7. · 2.00 Impact Factor
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ABSTRACT: Although cardiac tamponade is a well-known complication of malignancy, it is uncommon as the initial manifestation. The antemortem diagnosis is difficult and distant metastasis is extremely rare. The presentations of primary pericardial mesothelioma are nonspecific. Pathologically, mesothelioma is the most common in primary tumors of the pericardium. Radical surgery can be used to treat a localized mesothelioma. However, the therapy for advanced primary pericardial mesothelioma is usually palliative because it is resistant to irradiation, and chemotherapy does not markedly improve the outcome. The prognosis is uniformly poor. The median survival from the onset of symptoms is 6 months. We present a 67-year-old woman with cardiac tamponade 4 months prior to a definitive diagnosis of primary pericardial mesothelioma. A computed tomogram confirmed multiple well-enhanced nodules in the pericardium, lungs and liver. Unfortunately, the patient died of multiple organ failure.
Changgeng yi xue za zhi / Changgeng ji nian yi yuan = Chang Gung medical journal / Chang Gung Memorial Hospital. 01/1999; 21(4):498-502.
