[Show abstract][Hide abstract] ABSTRACT: Hepatoma-derived growth factor (HDGF) is a unique nuclear/growth factor that plays an important role in the progression of different types of cancer. A total of 63 patients with early-stage cervical adenocarcinoma (Cx) were enrolled in this retrospective study. The expression of HDGF was significantly increased compared with adjacent non-tumor tissue samples (p < 0.001). Moreover, elevated nuclear HDGF levels were correlated with lymph-vascular space invasion (LVSI; p < 0.05), lymph node metastasis (LNM; p < 0.001), recurrence (p < 0.001) and advanced grade (AG; p < 0.001). The growth of cervical cancer cells (Hela cells) was enhanced by HDGF treatment. The HDGF mRNA and protein level were significantly higher in malignant cervical cancer cells compared with primary ones. By adenovirus gene delivery, HDGF overexpression enhanced, whereas HDGF knockdown perturbed the tumorigenic behaviors of cervical cancer cells. HDGF overexpression is common in early-stage cervical adenocarcinoma and is involved in the carcinogenesis of cervical adenocarcinoma. Cytoplasmic HDGF expression is strongly correlated with pelvic lymph node metastasis and recurrence, indicating that HDGF may serve as a novel prognostic marker for patients with Cx.
Preview · Article · Nov 2014 · International Journal of Molecular Sciences
[Show abstract][Hide abstract] ABSTRACT: Background:
Hypertrophic mediastinal parathyroid glands (HMPGs) play a role in recurrent secondary hyperparathyroidism (SHPT). Thoracoscopic retrieval of HMPGs has been proposed.
Twelve patients with recurrent SHPT owing to HMPGs were enrolled. We divided the locations of HMPGs below the innominate vein and right to the ascending aorta as Zone I, those below the innominate vein and left to the ascending aorta as Zone II, and those between the aortic arch and pulmonary artery as Zone III. Sestamibi scans combined with computed tomography (CT) scans were arranged to identify the location of HMPGs. Three trocars of the right or left thoracoscopic approach were applied for Zone I or Zone II; four trocars of the left thoracoscopic approach were applied for Zone III.
Sestamibi and CT scans could positively find the 15 parathyroid glands of the 12 patients. Thirteen HMPGs were retrieved successfully with a thoracoscopic approach. The mean operation time was 155 min (range 80-292) and the mean hospital stay was 5.9 days (4-8). After a mean follow-up of 29.6 months (3-61), calcium and intact parathyroid hormone levels returned to normal ranges in all patients except for one who preferred two-stage surgery. Neither perioperative mortality, nor major complications occurred.
HMPGs in recurrent SHPT may be multiple. Sestamibi scans combined with CT scans can guide optimal approaches. The thoracoscopic approach provides a safe and feasible technique in retrieving HMPGs in Zones I or II using 3 trocars. For HMPGs in Zone III, they should be handled with care using 4 trocars.
No preview · Article · Sep 2014 · World Journal of Surgery
[Show abstract][Hide abstract] ABSTRACT: Mucosa associated lymphoid tissue lymphoma (MALT lymphoma) is mostly seen in the gastrointestinal tract; origin from the kidney is extremely rare. Waldenström macroglobulinemia (WM) is a clinicopathologic syndrome denoted by the presence of monoclonal gammopathy in the serum, typically caused by lymphoproliferative disorder. Literature review did not find any report of renal MALT lymphoma accompanied by WM. Herein, for the first time, we report a 72 year-old female patient with a history of chronic kidney disease, presenting with solitary renal mass; MALT lymphoma was confirmed by pathological examination. A serology study identified the presence of WM. No manifestation of hyperviscosity syndrome was noted. Bone marrow biopsy disclosed the concurrent systemic involvement. Her treatment response was uneventful and the renal mass responded with regressive change in size after chemotherapy. The renal function remained stable during follow-up. MALT lymphoma should be considered as an underlying pathology of isolated renal mass. Furthermore, patients with MALT lymphoma should be screened for Waldenström macroglobulinemia and hyperviscosity syndrome.
No preview · Article · Apr 2014 · Journal of the Formosan Medical Association
[Show abstract][Hide abstract] ABSTRACT: Nasopharyngeal carcinoma (NPC) is known for its high metastatic potential and locoregional recurrence, although the molecular alterations that are driving NPC metastasis remain unclear at this time. This study aimed to examine the expression of fibulin-5 in NPC, correlate the results with clinicopathological variables and survival, and to investigate the role of fibulin-5 in human NPC cell lines.
Standard semi-quantitative-RT-PCR, quantitative-RT-PCR, immunoblotting, and immunohistochemistry were used to investigate the mRNA and protein expression profiles of fibulin-5 in normal and NPC tissues. Immunohistochemistry of fibulin-5 was correlated with clinicopathological characteristics by univariate analyses. NPC cells overexpressing fibulin-5 or fibulin-5-siRNA cells were generated by stable transfection to characterize the molecular mechanisms of fibulin-5-elicited cell growth and metastasis.
Our results demonstrated that fibulin-5 overexpression in NPC specimens and significantly correlated with advanced tumor metastasis indicating a poor 5-year overall survival. Fibulin-5 was mainly expressed in the nucleus in human NPC specimens and cell lines. Functionally, fibulin-5 overexpression yielded fast growth in NPC cells. In addition, fibulin-5 promotes cell metastasis in NPC cells through increased FLJ10540 and phosphor-AKT activity. In contrast, siRNA depletion of fibulin-5 suppressed FLJ10540 expression and phosphor-AKT activity. Suppression of either fibulin-5 or FLJ10540 can cause significant inhibition with regards to cell motility in NPC cells. Finally, immunohistochemical analysis of human aggressive NPC specimens showed a significant and positive correlation between fibulin-5 and FLJ10540 expression.
Higher fibulin-5 expression is not only an important indicator of poor survival, but also contributes to the development of new therapeutic strategies in the FLJ10540/AKT pathway for NPC treatment.
[Show abstract][Hide abstract] ABSTRACT: Follicular thyroid carcinoma (FTC) with sternum metastasis is rarely reported. Conservative treatments always result in a poor prognosis. We report two cases of FTC presenting with a large symptomatic solitary metastatic lesion in the sternum. Surgical intervention included total thyroidectomy, combined with wide composite resection of the sternal manubrium, as well as the adjacent clavicular head and ribs. A large defect with exposed pericardium and great vessels was found post resection in both cases. Because the ipsilateral vessels were sacrificed, a contralateral extended pedicled pectoralis major adipofascial flap was designed and transposed to cover the underlying vital organs. The patients received both adjuvant I-131 and radiotherapy postoperatively. The treatment was uneventful, and the patients are well and asymptomatic 5 years after the treatment. Wide composite resection and appropriate adjuvant therapies may offer a survival benefit in patients with advanced FTC with sternum metastasis.
[Show abstract][Hide abstract] ABSTRACT: Expression of toll-like receptor-4 (TLR4) on tumor cells is known to mediate innate immune responses that influence tumor cell growth and migration. This study aimed to characterize TLR4 expression and elucidate its functional significance in human hepatoblastoma (HB) cells.
Immunohistochemistry (IHC) was used to determine TLR4 expression level and its distribution pattern in HB liver tissues. Transcripts of tumor necrosis factor (TNF)-α, interleukin (IL)-8, matrix metalloproteinase (MMP)-2, MMP-13, tissue inhibitor of metalloproteinases (TIMP)-1, and TIMP-2 in HB HepG2 cells with lipopolysacharide (LPS) treatment were measured by quantitative PCR. Soluble cytokines and peptides in conditioned media were measured by ELISA. MMP-2 activity was determined by using gelatin zymography. Cell motility and invasiveness was determined using wound healing migration and Matrigel invasion assays, respectively.
TLR4 IHC staining demonstrated that TLR4 overexpression in HB liver tissues dramatically vanished after chemotherapy. In vitro study using an HB cell line, HepG2, showed that TLR4 agonist, LPS, significantly decreased transcripts of IL-8 and TNF-α, but did not affect MMP-13 mRNA level. By contrast, LPS only down-regulated IL-8 production and MMP-2 gelatinolytic activity. The latter might be in part due to the increased levels of MMP-2/TIMP-2 complex in conditioned media, thus leading to the decreased motility and invasiveness of HepG2 cells.
HB cells overexpress TLR4, whereas TLR4 agonistic treatment inhibits migration and invasion of HB HepG2 cells. These findings suggest that TLR4 signaling pathway is a potential therapeutic target for control of HB tumor progression. Pediatr Blood Cancer 2013;60:248–253.
Full-text · Article · Feb 2013 · Pediatric Blood & Cancer
[Show abstract][Hide abstract] ABSTRACT: Implantation of TheraCyte 4 × 10(6) live parathyroid cells can increase the bone marrow density of the spine of ovariectomized rats. There has been no published study examining the effect of such implantation on spinal fusion outcomes. The purpose of this study was to examine the effect of TheraCyte-encapsulated parathyroid cells on posterolateral lumbar fusions in a rat model.
Forty Sprague-Dawley rats underwent single-level, intertransverse process spinal fusions using iliac crest autograft. The rats were randomly assigned to two groups: Group 1 rats received sham operations on their necks (control; N = 20); Group 2 rats were implanted with TheraCyte-encapsulated 4 × 10(6) live parathyroid cells into the subcutis of their necks (TheraCyte; N = 20). Six weeks after surgery the rats were killed. Fusion was assessed by inspection, manual palpation, radiography, and histology. Blood was drawn to measure the serum levels of calcium, phosphorus, and intact parathyroid hormone (iPTH).
Based on manual palpation, the control group had a fusion rate of 33 % (6/18) and the TheraCyte group had a fusion rate of 72 % (13/18) (P = 0.044). Histology confirmed the manual palpation results. Serum iPTH levels were significantly higher in the TheraCyte group compared with the control group (P < 0.05); neither serum calcium nor phosphorus levels were significantly different between the two groups.
This pilot animal study revealed that there were more fusions in rats that received TheraCyte-encapsulated 4 × 10(6) live parathyroid cells than in control rats without significant change in serum calcium or phosphorus concentrations. As with any animal study, the results may not extrapolate to a higher species. Further studies are needed to determine if these effects are clinically significant.
Preview · Article · Jul 2012 · European Spine Journal
[Show abstract][Hide abstract] ABSTRACT: Kawasaki disease (KD) of unknown immunopathogenesis is an acute febrile systemic vasculitis and the leading cause of acquired heart diseases in childhood. To search for a better strategy for the prevention and treatment of KD, this study compared and validated human KD immunopathogenesis in a mouse model of Lactobacillus casei cell wall extract (LCWE)-induced coronary arteritis.
Recruited subjects fulfilled the criteria of KD and were admitted for intravenous gamma globulin (IVIG) treatment at the Kaohsiung Chang Gung Memorial Hospital from 2001 to 2009. Blood samples from KD patients were collected before and after IVIG treatment, and cardiovascular abnormalities were examined by transthoracic echocardiography. Wild-type male BALB/c mice (4-week-old) were intraperitoneally injected with LCWE (1 mg/mL) to induce coronary arteritis. The induced immune response in mice was examined on days 1, 3, 7, and 14 post injections, and histopathology studies were performed on days 7 and 14.
Both human KD patients and LCWE-treated mice developed coronary arteritis, myocarditis, valvulitis, and pericarditis, as well as elevated plasma levels of interleukin (IL)-2, IL-6, IL-10, monocyte chemoattractant protein (MCP)-1, and tumor necrosis factor (TNF)-α in acute phase. Most of these proinflammatory cytokines declined to normal levels in mice, whereas normal levels were achieved in patients only after IVIG treatment, with a few exceptions. Toll-like receptor (TLR)-2, but not TLR4 surface enhancement on circulating CD14+ monocytes, was augmented in KD patients before IVIG treatment and in LCWE-treated mice, which declined in patients after IVIG treatment.
This result suggests that that not only TLR2 augmentation on CD14+ monocytes might be an inflammatory marker for both human KD patients and LCWE-induced CAL mouse model but also this model is feasible for studying therapeutic strategies of coronary arteritis in human KD by modulating TLR2-mediated immune activation on CD14+ monocytes.
[Show abstract][Hide abstract] ABSTRACT: Nasopharyngeal carcinoma (NPC) is well-known for its highly metastatic characteristics, but little is known of its molecular mechanisms. New biomarkers that predict clinical outcome, in particular the ability of the primary tumor to develop metastatic tumors are urgently needed. The aim of this study is to investigate the role of FLJ10540 in human NPC development.
A bioinformatics approach was used to explore the potentially important regulatory genes involved in the growth/metastasis control of NPC. FLJ10540 was chosen for this study. Two co-expression strategies from NPC microarray were employed to identify the relationship between FLJ10540 and osteopontin. Quantitative-RT-PCR, immunoblotting, and immunohistochemistry analysis were used to investigate the mRNA and protein expression profiles of FLJ10540 and osteopontin in the normal and NPC tissues to confirm microarray results. TW01 and Hone1 NPC cells with overexpression FLJ10540 or siRNA to repress endogenous FLJ10540 were generated by stable transfection to further elucidate the molecular mechanisms of FLJ10540-elicited cell growth and metastasis under osteopontin stimulation.
We found that osteopontin expression exhibited a positive correlation with FLJ10540 in NPC microarray. We also demonstrated comprehensively that FLJ10540 and osteopontin were not only overexpressed in NPC specimens, but also significantly correlated with advanced tumor and lymph node-metastasis stages, and had a poor 5-year survival rate, respectively. Stimulation of NPC parental cells with osteopontin results in an increase in FLJ10540 mRNA and protein expressions. Functionally, FLJ10540 transfectant alone, or stimulated with osteopontin, exhibited fast growth and increased metastasis as compared to vehicle control with or without osteopontin stimulation. Conversely, knockdown of FLJ10540 by siRNA results in the suppression of NPC cell growth and motility. Treatment with anti-CD44 antibodies in NPC parental cells not only resulted in a decrease of FLJ10540 protein, but also affected the abilities of FLJ10540-elicited cell growth and motility in osteopontin stimulated-NPC cells.
These findings suggest that FLJ10540 may be critical regulator of disease progression in NPC, and the underlying mechanism may involve in the osteopontin/CD44 pathway.
Full-text · Article · May 2012 · Journal of Translational Medicine
[Show abstract][Hide abstract] ABSTRACT: Kawasaki disease (KD) is not only the leading cause of childhood acquired heart diseases, but also causes profound coronary artery sequelae due to chronic vascular inflammation in adulthood. Of unknown underlying mechanism, both innate and adaptive immune responses are involved in the pathogenesis of coronary artery lesions (CALs). We investigated the role of dectin-1/spleen tyrosine kinase (Syk) pathway on macrophage in responsive to Lactobacillus casei cell wall extract (LCWE) in vitro and in vivo. We found that LCWE induced in vitro macrophage activation with increased production of IL-6, TNF-α, and MCP-1, concomitantly with Syk activation, and dectin-1 and TLR2 enhancement. In vivo, LCWE induced infiltration of dectin-1(+) macrophages into CALs and cardiac upregulation of IL-6 and MCP-1 on day 14 post-injection. Most importantly, Syk inhibition alleviated LCWE-induced arteritis in BALB/c mice. Blockade of either dectin-1 or Syk significantly inhibited LCWE-induced IL-6 and MCP-1 production both in vitro and in vivo. This study demonstrates that the macrophage dectin-1/Syk-mediated pathway is involved in LCWE-induced CALs and production of IL-6 and MCP-1. Given the functional equivalence of human dectin-1 to murine, the importance of dectin-1/Syk pathway in the development of murine CALs warrants further investigation on their roles in human KD.
[Show abstract][Hide abstract] ABSTRACT: Recent studies have demonstrated an increase in the incidence of HPV-associated oral squamous cell carcinoma. The aim of this study was to investigate the presentation of HPV in verrucous and papillary lesions of the oral mucosa and the relationship with the prognosis of the patients.
Fifty-three biopsy specimens from 31 patients were investigated by polymerase chain reaction using a consensus primer directed to the HPV L1 gene; this was followed by a confirmatory in situ hybridization to identify the HPV types.
Fifteen tumor biopsies (28.3%) were positive for the HPV L1 gene, but only 8 specimens (15.1%) were found to be positive using in situ hybridization. The positive rates of HPV L1 gene were 58.8% and 13.9% in malignant and benign verrucous lesions, respectively. HPV infection is independently associated with malignant transformation and disease-specific survival.
The presence of HPV infection is relatively low; however, the clinical outcome of patients with HPV-positive papillary and verrucous lesions was poor.
[Show abstract][Hide abstract] ABSTRACT: Chen T-J, Huang S-C, Huang H-Y, Wei Y-C, Li C-F. Rsf-1/HBXAP overexpression is associated with disease-specific survival of patients with gallbladder carcinoma. APMIS 2011; 119: 808–14.
Dysregulated chromatin remodeling often leads to abnormal gene expression or silencing in cells, thereby implicating tumor development and progression. As a subunit of remodeling and spacing factor (RSF) complex, Rsf-1, a novel nuclear protein with histone chaperon function, mediates ATPase-dependent chromatin remodeling and confer tumor aggressiveness in common carcinomas. We aimed, for the first time, to evaluate the Rsf-1 expression status and its associations with clinicopathological features and patient survival in a well characterized cohort of gallbladder carcinomas. Using tissue microarray-based immunohistochemistry, we assessed Rsf-1 expression in gallbladder carcinomas, yielding 88 cases undergoing surgical intervention with interpretable results. The Rsf-1 overexpression, present in 61 cases (69.3%), was significantly associated with higher histological grades (p = 0.002) and vascular invasion (p = 0.037) and marginally with non-papillary histotypes (p = 0.058). In univariate log-rank analysis, Rsf-1 overexpression was significantly predictive of disease-specific survival (p = 0.0015), which remained prognostically independent [p = 0.0191, risk ratio (RR) = 2.683], along with American Joint Committee on Cancer stages II–IV (p = 0.0265, RR = 2.102). Our findings indicate that Rsf-1 overexpression is common and associated with adverse prognosticators in gallbladder carcinomas. It may confer tumor aggressiveness through chromatin remodeling and represents a potential prognostic biomarker of gallbladder carcinomas.
[Show abstract][Hide abstract] ABSTRACT: Absent pulmonary valve syndrome is rare. We report the case of a child with absent pulmonary valve syndrome noted after birth. Progressive dilatation of the main pulmonary artery and ascending aorta were noted by echocardiography and confirmed by heart computed tomography. He underwent ascending aorta graft replacement and pulmonary artery reduction angioplasty at the age of 6. Good outcome was achieved at 18-month follow-up where subsequent computed tomography revealed a normal size ascending aorta and main pulmonary artery.
No preview · Article · Sep 2010 · Heart and Vessels
[Show abstract][Hide abstract] ABSTRACT: The use of nonionic polymeric micelles orally to protect and deliver plasmid DNA in vivo was investigated. Parathyroid hormone (PTH)(1-34) gene (179 bp) was inserted into a human cytomegalovirus promoter (PCMV) and E. coli competent cells were used to amplify the cDNA. Polymeric micelle formations (100 microl) formed from PCMV-PTH(1-34) cDNA (7.2 microg/microl) and 6% (w/v) polyethylene oxide-polypropylene oxide-polyethylene oxide (PEO-PPO-PEO) was administered at 8-hr intervals for 48 hr and then at 8-hr intervals for 24 hr weekly for 3 weeks. Parathyroidectomized rats receiving 150 microl of EDTA (10 mM) before each dose of formation served as the study group; rats receiving drinking water, EDTA (10 mM), PCMV-PTH(1-34) cDNA and PCMV-PTH(1-34) cDNA plus EDTA at the same amount and time intervals served as the control groups. Serum levels of calcium and PTH(1-34) were measured weekly for 4 weeks. Immunohistochemical stain for PTH(1-34), reverse transcriptase polymerase chain reaction for PTH(1-34) mRNA and the relative density of PTH(1-34) mRNA were performed at 2 and 4 weeks after oral gene therapy in different organs. One third to three of five rats in the control groups died after parathyroidectomy. Serum levels of calcium and PTH(1-34) were higher in the study than in the control groups. In the study group, positive stain of PTH(1-34) and PTH(1-34) mRNA could be found in those organs. Relative densities of PTH(1-34) mRNA were higher in the study than in the drinking water group in different organs. Oral gene therapy can maintain calcium and PTH(1-34) levels in parathyroidectomized rats.
No preview · Article · Aug 2009 · Human gene therapy
[Show abstract][Hide abstract] ABSTRACT: The authors present the case of a 55-year-old woman with a nonfunctioning intrapericardial paraganglioma. The tumor was incidentally found during transthoracic echocardiography that was performed because an enlarged cardiac silhouette had been noted on a chest x-ray. Transesophageal echocardiography further elucidated that the left circumflex coronary artery branched and traversed into the intrapericardial mass. Coronary angiography and cardiac multislice computed tomography both confirmed the presence of a vascular intrapericardial mass being fed by the obtuse marginal artery. Moreover, an arterial aneurysmal formation and a coronary arteriovenous fistula were noted within the tumor. After "en bloc" tumor resection, histopathologic and electron microscopic examinations established the diagnosis of a nonfunctioning intrapericardial paraganglioma.
Preview · Article · Feb 2009 · Journal of the American Society of Echocardiography: official publication of the American Society of Echocardiography
[Show abstract][Hide abstract] ABSTRACT: To investigate COX-2 expression in carcinoma and stromal cells in patients with urothelial carcinoma of upper urinary tracts (UCUUT) and determine whether expression patterns are associated with clinical characteristics and survival.
We performed immunohistochemistry for COX-2 on paraffin-embedded tumors of UCUUT specimens from 79 patients. We evaluated the level of expression in carcinoma cells, presence of stromal cell expression, and infiltration of inflammatory cells.
We observed strong and moderate expression of COX-2 in carcinoma cells in 19 (24.1%) and 46 (58.2%) cases, respectively. In 36 (45.6%) cases COX-2 expression was present in stromal cells. The level of COX-2 expression in carcinoma cells was not correlated with pathological stage (P = 0.22) or grade (P = 0.45). COX-2 expression in stromal cells was correlated with high stage (P <0.0001) and high grade (P <0.0001). The patient's survival was reduced if the tumor revealed strong or moderate expression of COX-2 in carcinoma cells (P = 0.03), the presence of COX-2 expression in stromal cells (P <0.0001), and infiltrating inflammatory cells (P = 0.0001), by log-rank test. Prognosis was poor if the tumor was positive for both COX-2 expression in stromal cells and inflammatory cell infiltrate (P <0.0001).
COX-2 expression in stromal cells shows greater correlation with high stage and high grade than COX-2 expression in carcinoma cells. Stromal COX-2 expression may be used as a marker of invasiveness and poor prognosis for patients with UCUUT.
[Show abstract][Hide abstract] ABSTRACT: Valvular heart disease has become an important public health concern. The increased wall stress and underlying disease entity associated with mitral valve disease provide unfavorable circumstances for atrial cardiomyocytes. The expression of the alpha-smooth muscle actin isoform is considered characteristic of cardiomyocyte dedifferentiation (embryonic cardiomyocyte), and cardiomyocyte dedifferentiation may indicate an adaptive state, enabling cardiomyocytes to survive despite unfavorable circumstances.
This study comprised 20 adult patients with symptomatic severe mitral valve disease and moderate to severe tricuspid valve disease and without coronary artery disease undergoing valve operations for congestive heart failure. Ten patients had persistent atrial fibrillation and 10 patients had never been in atrial fibrillation by history and electrocardiograms before surgery. Atrial tissues of the right atrial appendage were obtained during surgery.
Immunohistochemical study demonstrated that alpha-smooth muscle actin protein expression was not altered by atrial fibrillation, and alpha-smooth muscle actin protein expression in atrial tissues was higher in patients with sinus rhythm than in those with atrial fibrillation (the percentage of cells that were alpha-smooth muscle actin-positive was 51.5+/-34.9% for right atria from patients in sinus rhythm vs. 16.2+/-15.0% for right atria from patients with atrial fibrillation) (P<.03). Semiquantitation of alpha-smooth muscle actin by immunoblotting of extracts from atrial tissues showed similar findings as in the immunohistochemical observations: that is, atrial fibrillation did not influence the expression of alpha-smooth muscle actin protein. Interstitial fibrosis represented 43.2+/-13.9% of the right atrial tissue in the sinus group, whereas interstitial fibrosis comprised 49.8+/-8.2% of the right atrial tissue in the atrial fibrillation group (P=.320).
Dedifferentiation of atrial cardiomyocytes occurs in patients with cardiac valve disease, even without atrial fibrillation.
No preview · Article · May 2008 · Cardiovascular Pathology