Publications by authors named "Tzu-Cheng Su"

24 Publications

  • Page 1 of 1

High Expression of MTA1 Predicts Unfavorable Survival in Patients With Oral Squamous Cell Carcinoma.

In Vivo 2021 Jul-Aug;35(4):2363-2368

School of Medicine, Chung Shan Medical University, Taichung, Taiwan, R.O.C.;

Background/aim: Metastasis-associated protein 1 (MTA1) plays a role in ATP-dependent nucleosome disruption activity and histone deacetylase activity and may indicate DNA methylation activity. MTA1 may also be involved in the progression of oral squamous cell carcinoma (OSCC).

Patients And Methods: MTA1 immunoreactivity was analyzed using immunohistochemical (IHC) staining analysis in specimens from 281 OSCC patients. Kaplan-Meier analysis was used to determine the prognostic value of MTA1 for overall survival.

Results: High MTA1 expression was significantly associated with female gender and lymph node metastasis. Multivariate analyses showed the independent prognostic role of high MTA1 expression in patients with OSCC of poorer mean survival.

Conclusion: MTA1 expression, detected by IHC staining, could be an independent prognostic marker for patients of OSCC.
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http://dx.doi.org/10.21873/invivo.12513DOI Listing
June 2021

Heat Shock Protein-70 Levels Are Associated With a State of Oxidative Damage in the Development of Bronchopulmonary Dysplasia.

Front Pediatr 2021 26;9:616452. Epub 2021 May 26.

Department of Pediatrics, Changhua Christian Children's Hospital, Changhua, Taiwan.

Heat shock protein-70 (Hsp-70) exhibits cytoprotective effects against oxidative stress-induced airway injury. This study aimed to examine Hsp-70 and 8-hydroxy-2'-deoxyguanosine (8-OHdG) from tracheal aspirates (TA) in very low-birth weight (VLBW) preterm infants to predict the development of bronchopulmonary dysplasia (BPD). This birth cohort study enrolled 109 VLBW preterm infants, including 32 infants who developed BPD. Hsp-70 and 8-OHdG concentrations from TA were measured by immunoassay. The apoptosis of TA epithelial cells obtained on Day 28 after birth was measured using annexin-V staining assay. Hsp-70 and 8-OHdG levels in TA fluid were persistently increased from Day 1 to Day 28 of life in the BPD group. Multiple linear regression analysis demonstrated that BPD was significantly associated with gestational age, respiratory distress syndrome, and TA Hsp-70 and 8-OHdG levels on post-natal Day 28. The TA Hsp-70 level positively correlated with TA 8-OHdG level on the Day 1 ( = 0.47) and Day 28 of life ( = 0.68). Incubation of recombinant Hsp-70 with primary epithelial cells derived from TA of patients decreased hydrogen peroxide-induced epithelial cell death. Hsp-70 levels are associated with a state of oxidative injury in the development of BPD.
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http://dx.doi.org/10.3389/fped.2021.616452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187579PMC
May 2021

Subcutaneous injection of recombinant heat shock protein 70 ameliorates atopic dermatitis skin lesions in a mouse model.

Kaohsiung J Med Sci 2020 Mar 6;36(3):186-195. Epub 2020 Jan 6.

Frontier Molecular Medical Research Center in Children, Changhua Christian Children Hospital, Changhua County, Taiwan.

Atopic dermatitis (AD) is a chronic inflammatory skin disease and sometimes is a tough challenge for physicians. We previously reported that in Th2 environment, the production and secretion of thymic stromal lymphopoietin (TSLP) from human keratinocytes was inhibited by recombinant heat shock protein 70 (rHSP70). The present study assessed the therapeutic effectiveness of rHSP70 in a mouse model of AD. An experimental model of AD was reproduced by systemic sensitization and local epicutaneous challenge with ovalbumin (OVA). Treatment of rHSP70 was performed by subcutaneous administration. The levels of OVA-specific IgE, as well as cytokines, were detected by ELISA. Skin samples from patch areas were also taken for histologic examination. Injection of rHSP70 improved the histologic picture by reducing the thickness of epidermis and allergic inflammation. Skin sonography revealed rHSP70 ameliorated skin remodeling. rHSP70 also significantly decreased the protein expression of TSLP of skin from patch areas. Furthermore, in ex vivo studies also showed group of rHSP70 treatment decreased IL-13, RANTES, MIP-1β and increased IFN-γ secreted from splenocytes stimulated with OVA. The rHSP70 intervention in the mouse model of AD reduced the skin expression of TSLP and attenuated the clinical appearance of OVA-induced AD mice. The effect was achieved by suppressed Th2 immune response in injected skin tissue and enhanced systemic Th1 immune response. These results suggest that rHSP70 have potential as a promising protein for the treatment of AD.
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http://dx.doi.org/10.1002/kjm2.12163DOI Listing
March 2020

Renal Tubular TRPA1 as a Risk Factor for Recovery of Renal Function from Acute Tubular Necrosis.

J Clin Med 2019 Dec 11;8(12). Epub 2019 Dec 11.

Institute of Clinical Medicine, National Yang-Ming University, Taipei 11221, Taiwan.

Background: Transient receptor potential ankyrin 1 (TRPA1), a redox-sensing Ca-influx channel, serves as a gatekeeper for inflammation. However, the role of TRPA1 in kidney injury remains elusive.

Methods: The retrospective cohort study recruited 46 adult patients with acute kidney injury (AKI) and biopsy-proven acute tubular necrosis (ATN) and followed them up for more than three months. The subjects were divided into high- and low-renal-tubular-TRPA1-expression groups for the comparison of the total recovery of renal function and mortality within three months. The significance of TRPA1 in patient prognosis was evaluated using Kaplan-Meier curves and logistic regression analysis.

Results: Of the 46 adult AKI patients with ATN, 12 totally recovered renal function. The expression level of tubular TRPA1 was detected by quantitative analysis of the immunohistochemistry of biopsy specimens from ATN patients. The AKI patients with high tubular TRPA1 expression showed a high incidence of nontotal renal function recovery than those with low tubular TRPA1 expression (OR = 7.14; 95%CI 1.35-37.75; = 0.02). High TRPA1 expression was independently associated with nontotal recovery of renal function (adjusted OR = 6.86; 95%CI 1.26-37.27; = 0.03).

Conclusion: High tubular TRPA1 expression was associated with the nontotal recovery of renal function. Further mechanistic studies are warranted.
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http://dx.doi.org/10.3390/jcm8122187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6947213PMC
December 2019

Cytoplasmic, nuclear, and total PBK/TOPK expression is associated with prognosis in colorectal cancer patients: A retrospective analysis based on immunohistochemistry stain of tissue microarrays.

PLoS One 2018 4;13(10):e0204866. Epub 2018 Oct 4.

Department of Surgical Pathology, Changhua Christian Hospital, Changhua, Taiwan.

Objective: PDZ-binding kinase/T-LAK cell-originated protein kinase (PBK/TOPK) regulates components of the cell cycle, including cell growth, immune responses, DNA damage repair, apoptosis, and inflammation. PBK/TOPK may also accelerate tumorigenesis in colorectal cancer.

Methods: We investigated the impact of PBK/TOPK on the clinical outcome of colorectal cancer patients to further identify its role in colorectal cancer. PBK/TOPK immunoreactivity was analyzed by immunohistochemistry in 162 cancer specimens from primary colorectal cancer patients.

Results: The mean follow-up time after surgery was 5.4 years (medium: 3.9 years; range 0.01 to 13.1 years). The prognostic value of PBK/TOPK on overall survival was determined by Kaplan-Meier analysis and Cox proportional hazard models. PBK/TOPK was expressed in both the cytoplasm and nucleus. High PBK/TOPK expression in tumor cells was significantly associated with advanced T value. The 5-year survival rate was greater for patients with high total PBK/TOPK expression than with low PBK/TOPK expression (58.3% vs 34.4%, P = 0.005). Multivariate analyses showed that low-scoring cytoplasmic PBK/TOPK, negative nuclear PBK/TOPK, low total PBK/TOPK, and advanced tumor stage were correlated with poor overall patient survival.

Conclusions: We suggest that PBK/TOPK expression, detected by IHC staining, could be used as an independent prognostic marker for colorectal cancer patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0204866PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6171876PMC
March 2019

Effects of vitamin B-6 supplementation on oxidative stress and inflammatory response in neonatal rats receiving hyperoxia therapy.

J Food Drug Anal 2018 07 2;26(3):1086-1096. Epub 2018 Feb 2.

Department of Nutrition, Chung Shan Medical University, Taichung, Taiwan; Department of Nutrition, Chung Shan Medical University Hospital, Taichung, Taiwan. Electronic address:

Hyperoxia is often used in the treatment of neonates. However, protracted use of hyperoxia leads to significant morbidity. The purpose of this study was to evaluate the effects of vitamin B-6 supplementation on oxidative stress and inflammatory responses in neonatal rats undergoing hyperoxia therapy. The study consisted of 2 parts: a survival study and a vitamin B-6 efficacy study for 16 days. Neonatal rats were randomly divided into either the control group, B-6 group (subcutaneously injected with 90 mg/kg/d of pyridoxal 5'-phosphate [PLP]), O group (treated with 85% oxygen), or O + B-6 group (simultaneously treated with 85% oxygen and 90 mg/kg/d PLP). After the survival study was done, the vitamin B-6 efficacy study was performed with duplicate neonatal rats sacrificed on the 3rd, 6th, 9th, and 16th day. Serum inflammatory cytokines, tissue pathology, and malondialdehyde (MDA) levels were measured. In the survival study, the survival rate of neonatal rats in the control, B-6, O, and O + B-6 group on the 16th day were 100%, 100%, 25%, and 62.50%, respectively. The efficacy study showed lung polymorphonuclear granulocyte (PMN) and macrophage infiltration, increased liver hemopoiesis, and higher MDA levels in liver homogenates at days 3 through 16 in the O group. Vitamin B-6 supplementation considerably increased serum inflammatory cytokines in either the 6th or 9th day and decreased liver MDA level before the 6th day. These results indicate that neonatal rats receiving hyperoxia treatment suffered divergent serum inflammatory responses and were in increased liver oxidative stress. Vitamin B-6 supplementation seemed to improve survival rates, change systemic inflammatory response, and decrease liver oxidative stress while neonatal rats were under hyperoxia treatment.
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http://dx.doi.org/10.1016/j.jfda.2018.01.004DOI Listing
July 2018

Tubular Peroxiredoxin 3 as a Predictor of Renal Recovery from Acute Tubular Necrosis in Patients with Chronic Kidney Disease.

Sci Rep 2017 02 27;7:43589. Epub 2017 Feb 27.

Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.

Peroxiredoxin 3 (PRX3) is a mitochondrial antioxidant that regulates apoptosis in various cancers. However, whether tubular PRX3 predicts recovery of renal function following acute kidney injury (AKI) remains unknown. This retrospective cohort study included 54 hospitalized patients who had AKI with biopsy-proven acute tubular necrosis (ATN). The study endpoint was renal function recovery within 6 months. Of the 54 enrolled patients, 25 (46.3%) had pre-existing chronic kidney disease (CKD) and 33 (61%) recovered renal function. Tubular PRX3 expression was higher in patients with ATN than in those without renal function recovery. The level of tubular but not glomerular PRX3 expression predicted renal function recovery from AKI (AUROC = 0.76). In multivariate Cox regression analysis, high PRX3 expression was independently associated with a higher probability of renal function recovery (adjusted hazard ratio = 8.99; 95% CI 1.13-71.52, P = 0.04). Furthermore, the discriminative ability of the clinical model for AKI recovery was improved by adding tubular PRX3. High tubular PRX3 expression was associated with a higher probability of renal function recovery from ATN. Therefore, tubular PRX3 in combination with conventional predictors can further improve recovery prediction and may help with risk stratification in AKI patients with pre-existing CKD.
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http://dx.doi.org/10.1038/srep43589DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5378910PMC
February 2017

The Prognostic Role of STEAP1 Expression Determined via Immunohistochemistry Staining in Predicting Prognosis of Primary Colorectal Cancer: A Survival Analysis.

Int J Mol Sci 2016 Apr 19;17(4). Epub 2016 Apr 19.

Department of Medical Technology, Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli 356, Taiwan.

STEAP1 (six transmembrane epithelial antigen of the prostate 1) is a transmembrane protein that functions as a potential channel or transporter protein. It is overexpressed in certain cancers and is viewed as a promising therapeutic target. However, the prognostic role of STEAP1 is still controversial, and no role for STEAP1 has yet been indicated in colorectal cancer. The aim of this study was to investigate the possible association of STEAP1 expression with colorectal cancer prognosis. STEAP1 expression was analyzed by immunohistochemical staining of a tissue array of 165 cancer specimens from primary colorectal cancer patients. The mean and medium follow-up times after surgery were 5.1 and 3.9 years, respectively. A total of 139 patients died during the 13 years of follow-up in the survey period. The prognostic value of STEAP1 with respect to overall survival was analyzed by Kaplan-Meier analysis and Cox proportional hazard models. In total, 164 samples displayed detectable STEAP1 expression in the cytoplasm and membrane. Low STEAP1 expression was correlated with poor overall survival (five-year survival: 33.7% vs. 57.0%, low expression vs. high expression, p = 0.020). Accordingly, multivariate analysis identified low STEAP1 expression as an independent risk factor (hazard ratio = 1.500, p = 0.018), especially in elderly patients or those with late stage cancers, late T values, and early N values. We suggest that analysis of STEAP1 expression by immunohistochemical staining could serve as an independent prognostic marker for colorectal patients. This finding should be validated by other investigative groups.
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http://dx.doi.org/10.3390/ijms17040592DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4849046PMC
April 2016

The Nitric Oxide Synthase Inhibitor NG-Nitro-L-Arginine Methyl Ester Diminishes the Immunomodulatory Effects of Parental Arginine in Rats with Subacute Peritonitis.

PLoS One 2016 23;11(3):e0151973. Epub 2016 Mar 23.

Division of General Pediatric Surgery, Department of Surgery, China Medical University Children's Hospital, Taichung, Taiwan.

The combined treatment of parenteral arginine and the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) have been shown to improve liver function and systemic inflammation in subacute peritonitic rats. Here, we investigated the effects of single and combined parenteral arginine and L-NAME treatments on leukocyte and splenocyte immunity. Male Wistar rats were subjected to cecal punctures and were intravenously given total parenteral nutrition solutions with or without arginine and/or L-NAME supplementations for 7 days. Non-surgical and sham-operated rats with no cecal puncture were given a chow diet and parenteral nutrition, respectively. Parenteral feeding elevated the white blood cell numbers and subacute peritonitis augmented the parenteral nutrition-induced alterations in the loss of body weight gain, splenomegaly, and splenocyte decreases. Parenteral arginine significantly increased the B-leukocyte level, decreased the natural killer T (NKT)-leukocyte and splenocyte levels, alleviated the loss in body weight gain and total and cytotoxic T-splenocyte levels, and attenuated the increases in plasma nitrate/nitrite and interferon-gamma production by T-splenocytes. L-NAME infusion significantly decreased NKT-leukocyte level, tumor-necrosis factor (TNF)-alpha production by T-splenocytes and macrophages, and interferon-gamma production by T-leukocytes, monocytes, and T-splenocytes, as well as increased interleukin-6 production by T-leukocytes and monocytes and nitrate/nitrite production by T-leukocytes. Combined treatment significantly decreased plasma nitrate/nitrite, the NKT-leukocyte level, and TNF-alpha production by T-splenocytes. Parenteral arginine may attenuate immune impairment and L-NAME infusion may augment leukocyte proinflammatory response, eliminate splenocyte proinflammatory and T-helper 1 responses, and diminish arginine-induced immunomodulation in combined treatment in subacute peritonitic rats.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0151973PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4805291PMC
August 2016

Opposing prognostic roles of nuclear and cytoplasmic RACGAP1 expression in colorectal cancer patients.

Hum Pathol 2016 Jan 21;47(1):45-51. Epub 2015 Sep 21.

Department of Surgical Pathology, Changhua Christian Hospital, Changhua 50006, Taiwan; Department of Medical Technology, Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli 35664, Taiwan; School of Medicine, Chung Shan Medical University, Taichung 40242, Taiwan. Electronic address:

Rac GTPase activating protein 1 (RACGAP1) plays a regulatory role in initiation of cytokinesis, control of cell growth and differentiation, and tumor malignancy, making it a potential prognostic biomarker. RACGAP1 is present in the nucleus, but a diffuse distribution in the cytoplasm also occurs. The aim of this study was to determine the impact of nuclear and cytoplasmic expression of RACGAP1 on clinical outcome to provide further evidence of a role in colorectal cancer. RACGAP1 expression was analyzed by immunohistochemistry in 166 cancer specimens from primary colorectal cancer patients. The mean follow-up time after surgery was 5.4 years (range, 0.01-13.10 years). The prognostic value of RACGAP1 on overall survival was validated by Kaplan-Meier analysis and Cox regression models. RACGAP1 is expressed in colorectal specimen and is present in both the nucleus and cytoplasm in different amounts. Colorectal cancer patients had opposite prognoses depending on the site of RACGAP1 expression. Patients with high nuclear RACGAP1 expression had poor outcomes, whereas those with high cytoplasmic RACGAP1 expression had favorable prognosis (P = .003 and P = .001, respectively). Patients with low nuclear but high cytoplasmic RACGAP1 expression had better survival compared with those with other combinations (P < .001). We suggest that RACGAP1 expression levels in the nucleus and cytoplasm, determined by immunohistochemical staining, predict opposite clinical outcomes and that both could be independent prognostic markers for colorectal cancer.
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http://dx.doi.org/10.1016/j.humpath.2015.09.002DOI Listing
January 2016

High nuclear/cytoplasmic ratio of Cdk1 expression predicts poor prognosis in colorectal cancer patients.

BMC Cancer 2014 Dec 15;14:951. Epub 2014 Dec 15.

School of Medicine, Chung Shan Medical University, Taichuang, Taiwan.

Background: Cdk1 (cyclin-dependent kinase 1) is critical regulator of the G2-M checkpoint. Cyclin-dependent kinase pathways are considered possible targets for cancer treatment; however, the prognostic role of Cdk1 in colorectal cancer is still controversial. Therefore, we attempted to determine the impact of Cdk1 on the clinical outcome of colorectal cancer patients to further identify its role in colorectal cancer.

Methods: Cdk1 immunoreactivity was analyzed by immunohistochemistry (IHC) in 164 cancer specimens from primary colorectal cancer patients. The medium follow-up time after surgery was 3.7 years (range: 0.01 to 13.10 years). The prognostic value of Cdk1 on overall survival was determined by Kaplan-Meier analysis and Cox proportional hazard models.

Results: All samples displayed detectable Cdk1 expression with predominant location in the cytoplasm and nucleus. A high Cdk1 nuclear/cytoplasmic (N/C) expression ratio was correlated with poor overall survival (5-year survival rate: 26.3% vs 46.9%, N/C ratio ≥1.5 vs N/C ratio <1.5, log-rank p = 0.027). Accordingly, a Cdk1 N/C expression ratio ≥1.5 was identified as an independent risk factor by multivariate analysis (hazard ratio = 1.712, P = 0.039).

Conclusions: We suggest that Cdk1 N/C expression ratio determined by IHC staining could be an independent prognostic marker for colorectal cancer.
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http://dx.doi.org/10.1186/1471-2407-14-951DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4302138PMC
December 2014

Inverse correlation of phospho-KDR/Flk-1 expression and stage of colorectal cancer: implication of the significance of neoangiogenesis in activated VEGFR-2 expressing early stage colorectal adenocarcinomas.

Pol J Pathol 2014 Oct;65(3):194-201

Hui-Ting Hsu, MD, 135 Nan-Hsiao St., Changhua 500-06, Department of Pathology, Changhua Christian Hospital, Changhua, Taiwan, tel. +886-4-7238595 ext. 4830, fax +886-4-7228289#3500, e-mail: (Hui-Ting Hsu).

The activation of vascular endothelial cell growth factor receptors (VEGFRs) plays an essential role in cancer progression. In this study, we investigated the expression of phosphorylated VEGFR-2 (or phospho-KDR/Flk-1), the activated form of VEGFR-2, in human colorectal adenomas and colorectal adenocarcinomas. Phospho-KDR/Flk-1 showed weak expression in the normal colorectal tissue. Phospho-KDR/Flk-1 was mainly stained in the cytoplasm of colorectal adenomas, and was stained in both the cytoplasm and nuclei colorectal adenocarcinomas. There was no indication of increased phospho-KDR/Flk-1 expression in the colorectal adenocarcinomas, as compared to that of colorectal adenomas. Furthermore, there was an inverse relationship of phospho-KDR/Flk-1 expression with cancer stage (p < 0.0001), lymph node metastasis (p = 0.011), and distant metastasis (p = 0.021) of the colorectal adenocarcinomas. Our results indicate that early stage colorectal adenocarcinomas with highly activated (phosphorylated) VEGFR-2 expression may indicate the significance of neoangiogenesis of the tumors.
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http://dx.doi.org/10.5114/pjp.2014.45781DOI Listing
October 2014

A case report: Blastic plasmacytoid dendritic cell neoplasm is misdiagnosed as breast infiltrating ductal carcinoma.

Int J Surg Pathol 2015 Feb 7;23(1):84-8. Epub 2014 Oct 7.

Changhua Christian Hospital, Changhua, Taiwan

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic tumor that typically occurs in older adults. Patients with BPDCN usually present with solitary or multiple skin lesions. Localized or disseminated lymphadenopathy at presentation is common. A case report illustrating histopathologically proven BPDCN initially misdiagnosed as breast infiltrating ductal carcinoma in a 39-year-old woman is presented. In this case, the patient presented with a breast mass without an obvious skin lesion initially. The morphology of the tumor cells mimicked high grade breast carcinoma cells. Without complete immunohistochemical study, this case was initially misdiagnosed as infiltrating ductal carcinoma. Reviewing the previous literature about BPDCN, no case with a breast mass and an absence of characteristic skin lesions initially has been reported. The purpose for which we are discussing this case is to reduce misdiagnosis when the initial symptom is unusual.
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http://dx.doi.org/10.1177/1066896914553662DOI Listing
February 2015

CSE1L modulates Ras-induced cancer cell invasion: correlation of K-Ras mutation and CSE1L expression in colorectal cancer progression.

Am J Surg 2013 Sep 24;206(3):418-27. Epub 2013 Jun 24.

Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Hsing-Yi District, Taiwan.

Background: Ras plays an important role in colorectal cancer progression. CSE1L (chromosome segregation 1-like) gene maps to 20q13, a chromosomal region that correlates with colorectal cancer development. We investigated the association of CSE1L with Ras in colorectal cancer progression.

Methods: The effect of CSE1L on metastasis-stimulating activity of Ras was studied in an animal model with tumor cells expressing CSE1L-specific shRNA and v-H-Ras. CSE1L expression was evaluated by the immunohistochemical analysis of 127 surgically resected colorectal tumors. K-Ras mutations were analyzed by direct sequencing.

Results: CSE1L knockdown reduced Ras-induced metastasis of B16F10 melanoma cells in C57BL/6 mice. v-H-Ras expression altered the cellular trafficking of CSE1L and increased CSE1L secretion. Most colorectal tumors were positive for CSE1L staining (98.4%, 125 of 127). Colorectal tumors with K-Ras mutation or high cytoplasmic CSE1L expression were correlated with T status (depth of tumor penetration; P = .004), stage (P = .004), and lymph node metastasis (P = .019).

Conclusions: CSE1L may be a target for treating Ras-associated tumors. Analysis of K-Ras mutation and CSE1L expression may provide valuable clinical and pathological information to aid in the determination of treatment options for colorectal cancer.
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http://dx.doi.org/10.1016/j.amjsurg.2012.11.021DOI Listing
September 2013

A rare malignant tumor of scalp in a 3-month-old Taiwanese infancy: case report of primitive myxoid mesenchymal tumor of infancy with molecular study.

Med Mol Morphol 2013 Jun 5;46(2):109-13. Epub 2013 Mar 5.

Department of Surgical Pathology, Changhua Christian Hospital, 135 Nanxiao Street, Changhua, Taiwan.

Primitive myxoid mesenchymal tumor of infancy is an extremely rare and recently recognized soft tissue tumor entity with a tendency for multiple recurrences. Only ten cases have been described in the literature and most cases are reported in Western countries. This tumor ranges in size from 2 to 15 cm and is characterized microscopically by a diffuse growth of primitive cells in a myxoid background with focal fascicles or a herringbone pattern. In this study, we describe a primitive myxoid mesenchymal tumor of infancy on the scalp of a 3-month-old Taiwanese boy. The histology showed typical morphology and the tumor cells showed vimentin and CD99 immunoreactivities. The translocation t(12,15)(p13;q25) was not found by fluorescence in situ hybridization. After complete surgical excision, no recurrence was noted during an 18-month follow-up.
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http://dx.doi.org/10.1007/s00795-013-0032-1DOI Listing
June 2013

Correlations between cytoplasmic CSE1L in neoplastic colorectal glands and depth of tumor penetration and cancer stage.

J Transl Med 2013 Jan 31;11:29. Epub 2013 Jan 31.

Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Hospital, No,250, Wu-Hsing St,, Taipei 11031, Taiwan.

Background: Colorectal carcinomas spread easily to nearby tissues around the colon or rectum, and display strong potential for invasion and metastasis. CSE1L, the chromosome segregation 1-like protein, is implicated in cancer progression and is located in both the cytoplasm and nuclei of tumor cells. We investigated the prognostic significance of cytoplasmic vs. nuclear CSE1L expression in colorectal cancer.

Methods: The invasion- and metastasis-stimulating activities of CSE1L were studied by in vitro invasion and animal experiments. CSE1L expression in colorectal cancer was assayed by immunohistochemistry, with tissue microarray consisting of 128 surgically resected specimens; and scored using a semiquantitative method. The correlations between CSE1L expression and clinicopathological parameters were analyzed.

Results: CSE1L overexpression was associated with increased invasiveness and metastasis of cancer cells. Non-neoplastic colorectal glands showed minimal CSE1L staining, whereas most colorectal carcinomas (99.2%, 127/128) were significantly positive for CSE1L staining. Cytoplasmic CSE1L was associated with cancer stage (P=0.003) and depth of tumor penetration (P=0.007). Cytoplasmic CSE1L expression also correlated with lymph node metastasis of the disease in Cox regression analysis

Conclusions: CSE1L regulates the invasiveness and metastasis of cancer cells, and immunohistochemical analysis of cytoplasmic CSE1L in colorectal tumors may provide a useful aid to prognosis.
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http://dx.doi.org/10.1186/1479-5876-11-29DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3564816PMC
January 2013

High nuclear expression of phosphorylated extracellular signal-regulated kinase in tumor cells in colorectal glands is associated with poor outcome in colorectal cancer.

Ann Diagn Pathol 2013 Apr 24;17(2):165-71. Epub 2012 Nov 24.

Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.

Extracellular signal-regulated kinase (ERK) is a major downstream transducer of Ras and plays an important role in transducing extracellular signals to the nuclei of cells. It is located in both the cytoplasm and the nucleus of cells. The nuclear localization of phosphorylated or activated ERK is involved in the invasive behavior of tumor cells. We studied the association between Ras mutation/ERK activation and the prognosis of patients with colorectal cancer. We analyzed 126 surgically resected colorectal cancer specimens for K-Ras mutation using direct sequencing. Activation/phosphorylation of ERK was assayed by immunohistochemistry with tissue microarray, and the staining intensity was analyzed using a semiquantitative scoring system. K-Ras mutations were detected in 32.5% (41/126) of the colorectal tumors. Colorectal glands are important functional organs in colorectal tissue and form the origin of colorectal carcinomas. Tissue microarray immunohistochemistry tests showed that tumors in colorectal cancer specimens were significantly stained for phospho-ERK (100%; 126/126), whereas nonneoplastic colorectal glands mainly showed faint phosphorylated ERK staining. High nuclear phospho-ERK expression in tumors was associated with highly invasive cancer stage and T status of the disease. Kaplan-Meier analysis showed that nuclear but not cytoplasmic phosphorylated ERK expression correlated with the patients' overall survival rate (P = .039). Colorectal adenomas including tubular adenomas and tubulovillous adenomas mainly showed weak cytoplasmic phospho-ERK expression. Our results suggest that immunohistologic analysis of phosphorylated ERK expression in colorectal glands may aid the diagnosis of colorectal cancer and that nuclear phosphorylated ERK might be a valuable prognostic marker for colorectal cancer.
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http://dx.doi.org/10.1016/j.anndiagpath.2012.09.004DOI Listing
April 2013

High expression of interleukin 10 might predict poor prognosis in early stage oral squamous cell carcinoma patients.

Clin Chim Acta 2013 Jan 12;415:25-30. Epub 2012 Sep 12.

Institute of Medicine, Chung Shan Medical University, Taichuang, Taiwan.

Background: Interleukin 10 (IL10) plays an important role in immunosuppression and suppression of antitumor immunity. This study examined the IL10 expression of tumor cells and assessed its significance in patients with oral squamous cell carcinoma (OSCC).

Methods: Tumor tissues and adjacent normal tissues were obtained from 325 patients with OSCC and were arranged in a tissue microarray. We examined 325 surgical specimens for associations between IL10 expression in tumor cells and clinical parameters of oral cancer.

Results: High IL10 expression in OSCC patients was significantly associated with male gender (P<0.001), smoking (P=0.015), alcohol consumption (P=0.018), betel quid chewing (P=0.003), poor relapse free survival (P=0.012), and poor overall survival (P=0.001). Patients with high IL10 expression, and particularly early stage OSCC patients, had significantly worse overall survival as defined by the log-rank test (P=0.014 for all cases; P=0.004 for early stage patients). In early stage patients, high IL10 expression in tumor cells was associated with poor prognosis (P=0.018) and a 1.99-fold higher death risk, as determined by Cox regression.

Conclusion: High IL10 expression is significantly associated with aggressive clinical manifestations and might be an independent survival predictor, particularly in early stage OSCC patients.
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http://dx.doi.org/10.1016/j.cca.2012.09.009DOI Listing
January 2013

Clinical-pathological correlation of K-Ras mutation and ERK phosphorylation in colorectal cancer.

Pol J Pathol 2012 Jun;63(2):93-100

Department of Pathology, Changhua Christian Hospital,Changhua, Taiwan.

The Ras-ERK pathway is frequently up-regulated in colorectal cancer. We analyzed the clinical-pathological correlation of K-Ras mutation and phospho-ERK expression in colorectal cancer. K-Ras mutations were detected in only 32.5% (41/126) of the colorectal cancer cases, while all cancers were positive for phospho-ERK staining. Colorectal cancer with wild-typeK-Ras and low phospho-ERK expression had a significantly higher survival rate (log-rank P = 0.04). There were 9 cases of K-Ras mutation/low phospho-ERK diseases; 88.9% (8/9) of them were stage III/IV diseases. High phospho-ERK expression was associated with a high stage and T status of the cancer, yet combined K-Ras mutation/phospho-ERK expression analysis further increased the efficiency of colorectal cancer prognosis. Our results demonstrate that Ras-ERK pathway correlated closely with colorectal cancer progression. Moreover, although colorectal cancer with K-Ras mutations has a more aggressive phenotype; the mutation rate is not very high. Phospho-ERK may be a useful marker in combination with K-Ras for improving the prognosis of colorectal cancer.
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June 2012

Vaginal superficial myofibroblastoma: a rare mesenchymal tumor of the lower female genital tract and a study of its association with viral infection.

Med Mol Morphol 2012 Jun 21;45(2):110-4. Epub 2012 Jun 21.

Department of Pathology, St. Martin de Porres Hospital, Chiayi, Taiwan.

Superficial myofibroblastoma is a rare mesenchymal tumor in the lower female genital tract. The exact etiology of superficial myofibroblastoma remains unclear. The association of viral infection and mesenchymal tumors has been well established in some particular types of soft tissue tumors. In the lower female genital tract, the intimate correlation of viral infection and tumor pathogenesis has been also proposed. We present a 59-year-old woman with postcoital bleeding for 1 month. The pelvic examination revealed a 2-cm polypoid mass mimicking leiomyoma at the vaginal fornix. Local excision was performed, and the pathological examination revealed a superficial myofibroblastoma. No tumor recurrence was noted during the 12-month follow-up. Pathological differential diagnosis of this tumor from other mesenchymal tumors is essential because of its distinct clinicopathological features. Furthermore, fluorescence in situ hybridization of human papilloma virus (HPV) and Epstein-Barr virus (EBV), as well as immunohistochemical staining of human herpesvirus 8 (HHV8), was negative in tumor cells. To the best of our knowledge, we are the first group to study the possible relationship of viral infection and the occurrence of this mesenchymal tumor. Our results suggested no association of vaginal superficial myofibroblastoma and infection with HPV, EBV, or HHV8.
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http://dx.doi.org/10.1007/s00795-011-0566-zDOI Listing
June 2012

Presence of CSE1L protein in urine of patients with urinary bladder urothelial carcinomas.

Int J Biol Markers 2012 Oct 8;27(3):e280-4. Epub 2012 Oct 8.

Division of Hematology and Oncology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan.

The chromosome segregation 1-like (CSE1L) protein is highly expressed in most cancers and has been shown to be secreted by tumor cells. We studied the presence of CSE1L in the urine of patients with bladder urothelial carcinomas. The results of our immunohistochemical analysis showed a high expression of CSE1L in bladder cancer specimens, while the normal bladder specimens only showed a very faint staining in some cells. Immunoblotting showed that CSE1L was present in urine of patients with bladder cancer. Urinary CSE1L-positive cases were detected in 95% (57/60) of patients with bladder urothelial carcinomas or the atypical/suspicious cases with urothelial atypia. No CSE1L was detected in urine of healthy controls (p<0.01). Our results suggest that urinary CSE1L deserves further evaluation for the screening of bladder cancer.
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http://dx.doi.org/10.5301/JBM.2012.9310DOI Listing
October 2012

The prognostic significance of nuclear CSE1L in urinary bladder urothelial carcinomas.

Ann Diagn Pathol 2012 Oct 2;16(5):362-8. Epub 2012 Apr 2.

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital, Taiwan.

Prognosis of urinary bladder urothelial carcinomas may be challenging; many tumors with similar histopathologic features show significantly different clinical outcomes. CSE1L, the chromosome segregation 1-like protein, is both a cytoplasmic and nuclear protein. We investigated the cytoplasmic/nuclear expression pattern of CSE1L to determine its potential prognostic significance. In immunohistochemical analysis, nonneoplastic urothelium showed faint CSE1L staining, whereas all tumors in the bladder cancer specimens had significant staining for CSE1L (100%, or 38/38). CSE1L cytoplasmic/nuclear staining was defined based on relative staining intensity. A total of 20 (52.6%) of 38 cancer specimens had strong nuclear CSE1L staining, and 44.7.3% (17/38) of the samples had strong cytoplasmic CSE1L staining. Bladder urothelial carcinomas with high CSE1L nuclear staining had a significantly lower overall survival rate (log-rank test, P = .011). CSE1L expression was not correlated with tumor stage, likely reflecting the faultiness of current urothelial carcinoma evaluation methods. Our results suggest that nuclear CSE1L may play an oncogenic role in bladder tumor progression and that immunohistochemical staining of nuclear CSE1L may be useful for the prognosis of bladder urothelial carcinomas.
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http://dx.doi.org/10.1016/j.anndiagpath.2012.02.005DOI Listing
October 2012

Lipomatous apocrine adenoma with syringocystadenoma papilliferum arising from the external auditory canal.

Head Neck Oncol 2011 Aug 22;3:36. Epub 2011 Aug 22.

Department of Surgical Pathology, Changhua Christian Hospital, Changhua, Taiwan.

A case of lipomatous tubular adenoma (LTA) with syringocystadenom papilliferum (SCAP) arising from the external auditory canal in a 25-year-old man is described and to the best of our knowledge through literature review, this kind of morphologic entity has not been reported before. Herein we reported the first case in the English literature in the world.
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http://dx.doi.org/10.1186/1758-3284-3-36DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3169502PMC
August 2011

Meigs' syndrome with elevated serum cancer antigen 125 levels in a case of ovarian sclerosing stromal tumor.

Taiwan J Obstet Gynecol 2011 Jun;50(2):196-200

Department of Surgical Pathology, Changhua Christian Hospital, Changhua, Taiwan.

Objective: Meigs' syndrome presenting as an ovarian tumor with elevated serum cancer antigen 125 (CA 125) levels is unusual. Only 37 cases have been reported, including three cases of ovarian sclerosing stromal tumor (SCT). Many reports have suggested that the presence of ascites is the major factor inducing mesothelial expression of CA 125.

Case Report: An 18-year-old woman presented with massive ascites, elevated serum CA 125 levels, and radiographic evidence of ovarian tumor. The histological and immunohistochemical examinations revealed a benign SCT.

Conclusion: SCT is a benign ovarian tumor and complete excision is curative. We also review all 37 cases and discuss possible mechanisms of Meigs' syndrome and elevated serum CA 125 level.
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http://dx.doi.org/10.1016/j.tjog.2011.01.011DOI Listing
June 2011
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