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Kun-Chun Chiang,
Chun-Nan Yeh,
Jun-Te Hsu, Ta-Sen Yeh,
Yi-Yin Jan,
Chun-Te Wu,
Huang-Yang Chen,
Shyh-Chuan Jwo,
Masashi Takano,
Atsushi Kittaka,
Horng-Heng Juang,
Tai C Chen
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ABSTRACT: Pancreatic cancer is a lethal disease with no known effective chemotherapy and radiotherapy, and most patients are diagnosed in the late stage, making them unsuitable for surgery. Therefore, new therapeutic strategies are urgently needed. 1α,25-dihydroxyvitamin D 3 [1α,25(OH) 2D 3] is known to possess antitumor actions in many cancer cells in vitro and in vivo models. However, its clinical use is hampered by hypercalcemia. In this study, we investigated the effectiveness and safety of a new generation, less calcemic analog of 1α,25(OH) 2D 3, 19-nor-2α-(3-hydroxypropyl)-1α,25-dihydroxyvitamin D 3 (MART-10), in BxPC-3 human pancreatic carcinoma cells in vitro and in vivo. We demonstrate that MART-10 is at least 100-fold more potent than 1α,25(OH) 2D 3 in inhibiting BxPC-3 cell proliferation in a time- and dose-dependent manner, accompanied by a greater upregulation of cyclin-dependent kinase inhibitors p21 and p27 and a greater downregulation of cyclin D3 and cyclin-dependent kinases 4 and 5, leading to a greater increase in the fraction of cells in G 0/G 1 phase. No induction of apoptosis and no effect on Cdc25 phosphatases A and C, were observed in the presence of either MART-10 or 1α,25(OH) 2D 3. In a xenograft mouse model, treatment with 0.3 µg/kg body weight of MART-10 twice/week for 3 weeks caused a greater suppression of BxPC-3 tumor growth than the same dose of 1α,25(OH) 2D 3 without inducing hypercalcemia and weight loss. In conclusion, MART-10 is a promising agent against pancreatic cancer growth. Further clinical trial is warranted.
Cell cycle (Georgetown, Tex.) 04/2013; 12(8). · 5.36 Impact Factor
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ABSTRACT: Background: Our aim is to identify the long-term relapse-free rate and predictive factors of response to splenectomy in adults with idiopathic thrombocytopenic purpura (ITP). Methods: Between 1999 and 2005, 54 patients of ITP, who underwent splenectomy in Chang Gung Memorial Hospital, Linkou, Taiwan were retrospectively reviewed. Various pre, intra and postoperative factors were analyzed to determine the predictive factors of response and long-term disease-free rate after splenectomy in adult patients. Results: The relapse free survival rates in complete response patients of splenectomy at 1-, 3- and 5-yr are 91.9%, 88.4%, and 88.4%, respectively. Younger age, response to steroids, pre- and postsplenectomy high platelet counts were found to be have significant p value of < 0.05 as predictive factors in univariate analysis. In multivariate analysis, only pre-op and post-op platelet counts were significant. Conclusions: Significant long-term relapse-free survival rate is achieved by splenectomy in adults with ITP. In univariate analysis, age, response to steroids, pre- and postsplenectomy platelet counts were the significant predictive factors of response. But in multivariate analysis, only pre-op and post-op platelet counts were significant.
Biomedical journal. 01/2013; 36(1):23-7.
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ABSTRACT: BACKGROUND: Despite advances in intensive care medicines, hemorrhagic shock leading to multiple organ failure remains the major causes of death in the injured host. Although studies have shown that 17β-estradiol (E2) prevents trauma-hemorrhage-induced lung damage, it remains unknown whether protein kinase B (Akt)/heme oxygenase (HO)-1 plays any role in E2-mediated lung protection after trauma-hemorrhage. MATERIALS AND METHODS: After a 5-cm midline laparotomy, male rats underwent hemorrhagic shock (mean blood pressure ∼40 mm Hg for 90 min) followed by fluid resuscitation. At the onset of resuscitation, rats were treated with vehicle, E2 (1 kg/mg), E2 plus phosphoinositide 3-kinase inhibitor LY294002 (5 mg/kg), or LY294002. At 2 h after trauma-hemorrhage or sham operation, lung tissue myeloperoxidase activity, wet-to-dry-weight ratio, inflammatory mediators, and apoptosis were measured. Lung Akt, HO-1, and cleaved caspase-3 protein levels were also determined. RESULTS: E2 attenuated the trauma-hemorrhage-induced increase in lung myeloperoxidase activity, edema formation, inflammatory mediator levels, and apoptosis, which was blocked by co-administration of LY294002. Administration of E2 normalized lung Akt phosphorylation and further increased HO-1 expression and decreased cleaved caspase-3 levels after trauma-hemorrhage. Co-administration of LY294002 prevented the E2-mediated attenuation of shock-induced lung injury. CONCLUSIONS: Our results collectively suggest that Akt-dependent HO-1 upregulation may play a critical role in E2-meditated lung protection after trauma-hemorrhage.
Journal of Surgical Research 11/2012; · 2.25 Impact Factor
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ABSTRACT: BACKGROUND: Adenocarcinoma of the body and tail of the pancreas are more often than not inoperable to begin with. Factors predicting the prognosis in the resected tumors of pancreatic body and tail were analyzed. METHODS: Between 1989 and 2006, 43 patients with adenocarcinoma of the body and tail of the pancreas underwent resection at Chang Gung Memorial Hospital, Taoyuan, Taiwan. Univariate and multivariate analysis of clinicopathological factors affecting the prognosis were analyzed. RESULTS: Totally, 32 patients were available for the analysis. The median follow-up was 13.6 months (1.5-87.5 months). The median survival time was 14.2 months and the 1-, 3-, and 5-year survival rates were 58.1, 25.8, and 6.5 %, respectively. On univariate analysis, the factors which influenced the survival were tumor size >4 cm (p = 0.004), lymphatic invasion (p = 0.001), and positive resection margin (p = 0.030). On multivariate analysis, only the tumor size and the lymphatic invasion were independent prognostic factors. CONCLUSION: Even after macroscopic curative resection, the prognosis remains poor for pancreatic body and tail adenocarcinoma. Early diagnosis is the key to achieving long-term survival. Newer effective adjuvant treatment after curative resection is needed to improve the survival.
Journal of Gastrointestinal Cancer 10/2012;
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ABSTRACT: Abstract Background: Acute small bowel obstruction (SBO) is a common cause of emergency hospital admission, often requiring surgical intervention. Herein, we describe the single-incision laparoscopic surgery (SILS) procedure for the management of SBO in the acute care setting. Patients and Methods: Patients with intestinal obstruction who underwent SILS in Chang Gung Memorial Hospital, Linkou, Taiwan, from January 2010 to January 2012 were retrospectively analyzed. Informed consent was obtained from all patients. Demographic information, intraoperative findings, surgery duration, and conversion to multi-incision laparoscopic surgery (MILS) were recorded. Postoperative records included the recovery period after surgery, complications, length of hospital stay, and final prognosis. Results: Ten SILS procedures for the repair of SBO were performed (six women, four men; median age, 52 years [range, 28-89 years]). Only 1 patient (10%) required conversion to MILS. The median operative time was 140 minutes (range, 90-210 minutes), median time to resume oral intake was 3 days (range, 1-7 days), median time to ambulation was 3 days (range, 1-6 days), and median postoperative hospital stay was 7.5 days (range, 3-14 days). There was no mortality in this series. All patients were discharged uneventfully. The umbilical incision was nearly invisible at the 1-month follow-up. The median follow-up time was 13.5 months (range, 4-26 months). No incisional hernias or adhesions were observed. Conclusions: SILS for SBO is a feasible, safe procedure that can be performed as initial treatment in select patients with bowel obstruction through resection and decompression of the small bowel using intra- or extracorporeal techniques, resulting in a nearly invisible scar.
Journal of Laparoendoscopic & Advanced Surgical Techniques 10/2012; · 1.40 Impact Factor
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ABSTRACT: BACKGROUND: This study aimed to reveal the predictors for the recurrence pattern of gastric cancer (GC) and analyze the prognostic factors in node-negative advanced (T2 to T4) GC after curative resection. METHODS: Between 1994 and 2006, 448 patients with node-negative advanced GC undergoing radical resection were enrolled in this study. Clinicopathologic factors affecting the recurrence pattern and prognosis for GC were analyzed. RESULTS: Location, size, tumor invasion depth, and perineural invasion were associated with tumor recurrence and outcome. T4 status was a predictor for locoregional recurrence and peritoneal seeding, and a large tumor size and the presence of perineural invasion predicted hematogenous spread. Patients with only locoregional recurrence had better survival than those with peritoneal seeding or hematogenous spread. CONCLUSIONS: In node-negative advanced GC, the prognostic factor differed significantly between locoregional recurrence/peritoneal seeding and hematogenous metastasis. Survival rates were higher in patients with locoregional recurrence alone than in patients with other recurrence patterns.
American journal of surgery 10/2012; · 2.36 Impact Factor
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ABSTRACT: Abstract Background: Surgery of gastrointestinal stromal tumors (GISTs) has been modified, and laparoscopic resection of GIST has gained improvement and roles. Patients and Methods: We retrospectively reviewed clinical data and oncological outcomes of our GIST patients who underwent laparoscopic surgery and traditional open surgery. In total, 227 pathologically diagnosed GIST cases were retrospectively reviewed in Chang Gung Memorial Hospital at Linkou, Taipei, Taiwan, between 2005 and 2010. We excluded those with tumor size >5 cm, biopsy-only, combined other operation, endoscopic mucosal resection, tumor located in the duodenum, colon-rectum, esophagocardiac junction, omentum, pelvic area, or retroperitoneum, or metastasis when operated on and those diagnosed as other disease after immunohistologic examination of GIST. Fifty-eight cases were enrolled, including 16 patients in the laparoscopic surgery group (LSG) and 42 patients in the open surgery group (OSG). The patients' demography, perioperative, pathologic result, and oncology result were recorded and analyzed. Results: Both groups showed no difference in clinical demography, tumor size, and locations. LSG patients showed fewer days to resume diet, shorter postoperative hospital stays, and less use of patient-controlled analgesia. The postoperative morbidity in LSG and OSG was 6.3% and 19%, respectively. The median follow-up time was 32.73 months in LSG and 39.75 months in OSG. Recurrence or metastasis was observed in 3 patients (1 in LSG and 2 in OSG). The recurrence rate between LSG and OSG showed no significant difference. Conclusions: Laparoscopic surgery was technically feasible for GIST of no more than 5 cm located at the stomach and small bowel. In the current study, we demonstrated that LSG patients benefited from fewer days to resume diet (5 versus 5.71 days), shorter postoperative stays (8 versus 9.07 days), and less patient-controlled analgesia use (6.7% versus 90.9%) during the perioperative period with the same short-term oncology result compared with OSG patients.
Journal of Laparoendoscopic & Advanced Surgical Techniques 09/2012; 22(8):758-63. · 1.40 Impact Factor
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ABSTRACT: Unsatisfying long-term survival of intrahepatic cholangiocarcinoma (ICC) triggers the clinicians searching for molecular markers, such as K-ras mutation, to tailor management strategy. Additionally, emergence of tyrosine kinase inhibitors (TKIs) brings new hope to palliate advanced ICC; whether the efficacy of TKIs is influenced by k-ras mutation is largely unknown. This study was designed to determine the prevalence of k-ras mutation and its clinical significance in ICC, as well as to pave the reference for future application of TKIs.
A total of 86 patients with ICC who underwent hepatectomy were retrospectively recruited. K-ras mutation was determined by using laser capture microdissection and direct sequencing method. Association among clinicopathological variables and K-ras mutation was analyzed. Prognostic factors of ICC after hepatectomy also were determined.
Nineteen (22%) patients exhibited K-ras mutations. Seventeen had their K-ras mutations occurring at codon 12, and the remaining two occurring at codon 13 and codon 61 in one each. Perineural invasion was exclusively the variable associated with K-ras mutation (odds ratio, 6.9) using logistic regression analysis. Multivariate analysis demonstrated that resection margin, T-status, nodal metastasis, and K-ras mutation were independent prognostic factors. The median survival of ICC patients with K-ras mutation was 5.7 months compared with 19.0 months in those without K-ras mutation (P = 0.002).
The prevalence of K-ras mutations in a considerably large cohort of ICC was 22%. K-ras mutation is strongly associated with perineural invasion phenotypically. K-ras mutation is an independent prognostic factor of ICC after hepatectomy.
Annals of Surgical Oncology 07/2012; 19 Suppl 3:S675-81. · 4.17 Impact Factor
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ABSTRACT: Although melatonin treatment following trauma-hemorrhage or ischemic reperfusion prevents organs from dysfunction and injury, the precise mechanism remains unknown. This study tested whether melatonin prevents liver injury following trauma-hemorrhage involved the protein kinase B (Akt)-dependent heme oxygenase (HO)-1 pathway. After a 5-cm midline laparotomy, male rats underwent hemorrhagic shock (mean blood pressure approximately 40 mmHg for 90 min) followed by fluid resuscitation. At the onset of resuscitation, rats were treated with vehicle, melatonin (2 mg/kg), or melatonin plus phosphoinositide 3-kinase (PI3K) inhibitor wortmannin (1 mg/kg). At 2 hr after trauma-hemorrhage, the liver tissue myeloperoxidase activity, malondialdehyde, adenosine triphosphate, serum alanine aminotransferase, and aspartate aminotransferase levels were significantly increased compared with sham-operated control. Trauma-hemorrhage resulted in a significant decrease in the Akt activation in comparison with the shams (relative density, 0.526 ± 0.031 versus 1.012 ± 0.066). Administration of melatonin following trauma-hemorrhage normalized liver Akt phosphorylation (0.993 ± 0.061), further increased mammalian target of rapamycin (mTOR) activation (5.263 ± 0.338 versus 2.556 ± 0.225) and HO-1 expression (5.285 ± 0.325 versus 2.546 ± 0.262), and reduced cleaved caspase-3 levels (2.155 ± 0.297 versus 5.166 ± 0.309). Coadministration of wortmannin abolished the melatonin-mediated attenuation of the shock-induced liver injury markers. Our results collectively suggest that melatonin prevents hemorrhagic shock-induced liver injury in rats through an Akt-dependent HO-1 pathway.
Journal of Pineal Research 05/2012; 53(4):410-6. · 5.79 Impact Factor
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ABSTRACT: Unusual hypervascularity is a hallmark of human hepatocellular carcinoma (HCC). Although microRNA-214 (miR-214) is upregulated in other human cancers, it is downregulated in HCC. We elucidated the biological and clinical significance of miR-214 downregulation in HCC.
MicroRNAs deregulated in HCC were identified using array-based microRNA profiling. A luciferase reporter assay confirmed target association between miR-214 and the hepatoma-derived growth factor (HDGF). Tube formation and in vivo angiogenesis assays validated the roles of miR-214/HDGF in angiogenesis.
miR-214 downregulation was associated with higher tumor recurrence and worse clinical outcomes. Ectopic expression of miR-214 suppressed xenograft tumor growth and microvascularity of the tumors and their surrounding tissues. The genes downregulated by ectopic expression of miR-214 were involved in the regulation of apoptosis, cell cycle, and angiogenesis. Integrated analysis disclosed HDGF as a downstream target of miR-214. Conditioned medium of HCC cells contained bioactivity to stimulate tube formation of human umbilical vein endothelial cells, which was abolished by pretreatment of the conditioned media with HDGF antibodies, suppression of HDGF expression or ectopic expression of miR-214 in the donor HCC cells. The angiogenic activity of the conditioned media, lost by ectopic expression of miR-214 in the donor cells, was restored by supplementation with recombinant HDGF. In vivo tumor angiogenesis assays showed significant suppression of tumor vascularity by ectopic expression of miR-214.
A novel role of microRNA in tumorigenesis is identified. Downregulation of miR-214 contributes to the unusual hypervascularity of HCC via activation of the HDGF paracrine pathway for tumor angiogenesis.
Journal of Hepatology 05/2012; 57(3):584-91. · 9.26 Impact Factor
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ABSTRACT: BACKGROUND: Pancreatic adenocarcinoma (PCA) is one of the most lethal human malignancies, and radical surgery remains the cornerstone of treatment. After resection, the overall 5-year survival rate is only 10% to 29%. At the time of presentation, however, about 40% of patients generally have distant metastases and another 40% are usually diagnosed with locally advanced cancers. The remaining 20% of patients are indicated for surgery on the basis of the results of preoperative imaging studies; however, about half of these patients are found to be unsuitable for resection during surgical exploration. In the current study, we aimed to determine the clinicopathological characteristics that predict the resectability of PCA and to conduct a prognostic analysis of PCA after resection to identify favorable survival factors. METHODS: We retrospectively reviewed the medical files of 688 patients (422 men and 266 women) who had undergone surgery for histopathologically proven PCA in the Department of Surgery at Chang Gung Memorial Hospital in Taiwan from 1981 to 2006. We compared the clinical characteristics of patients who underwent resection and patients who did not undergo resection in order to identify the predictive factors for successful resectability of PCA, and we conducted prognostic analysis for PCA after resection. RESULTS: A carbohydrate antigen 19-9 (CA 19-9) level of 37 U/ml or greater and a tumor size of 3 cm or more independently predicted resectability of PCA. In terms of survival after resection, PCA patients with better nutritional status (measured as having an albumin level greater than 3.5 g/dl), radical resection, early tumor stage and better-differentiated tumors were associated with favorable survival. CONCLUSIONS: Besides traditional imaging studies, preoperative CA 19-9 levels and tumor size can also be used to determine the resectability of PCA. Better nutritional status, curative resection, early tumor stage and well-differentiated tumors predict the favorable prognosis of PCA patients after resection.
World Journal of Surgical Oncology 05/2012; 10(1):77. · 1.12 Impact Factor
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ABSTRACT: Hepatoid differentiation in pancreatic carcinoma is a rare phenomenon. It occurs either as a pure form or as a component with other subtypes. Herein, we report a 52-year-old man with an ampullary large cell neuroendocrine carcinoma presenting with obstructive jaundice for 2 months. A 0.5-cm nodule was found in the pancreatic head. Morphologically, the nodule was composed of exclusively hepatocytic tumor cells and sinusoids with dysplastic cytology and capsular invasion. The patient did not have a hepatic mass or ectopic normal liver tissue. This is the first reported case of ampullary large cell neuroendocrine carcinoma coinciding with a pancreatic hepatoid microcarcinoma. The clinicopathological features of pancreatic hepatoid carcinomas and their histogenesis are discussed.
Chang Gung medical journal 05/2012; 35(3):285-91.
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ABSTRACT: The high incidence of gastric cancer among the octogenarians and nonagenarians (oldest old; age ≥ 80 years) is emerging as an important management issue. Herein, we report both the short-term outcomes and long-term survival results of standard radical gastrectomy in this group of patients.
This was a retrospective review of 164 oldest old patients (older group) and 2,258 younger patients (age <80 years; younger group) with gastric cancer who underwent curative resection between January 1994 and December 2006. Clinicopathologic data, long-term survival, and prognostic factors were analyzed.
Clinical tumor stage did not differ between the two groups at the time of diagnosis. Higher Charlson comorbidity index scores (≥ 5) were observed in the older group than in the younger group; this was associated with higher postoperative morbidity (P = 0.035) and in-hospital mortality rates (P = 0.015) in the older group. At a median follow-up of 37.8 months, the overall survival rate for the older group was lower than that for the younger group (P < 0.001). However, the cumulative incidence of gastric cancer-related deaths was comparable between the two groups. Nodal involvement and metastatic to retrieved lymph node ratio were the only independent predictors of survival in the older group.
Patients in the older group had a higher postoperative morbidity rate but comparable cancer-specific survival. Careful patient selection for gastrectomy is warranted in elderly patients, particularly those with high-grade nodal involvement.
Journal of Gastrointestinal Surgery 02/2012; 16(4):728-37. · 2.83 Impact Factor
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ABSTRACT: EphrinA5, a member of Eph/Ephrin family, possesses two alternative isoforms, large ephrinA5 isoform (ephrinA5L) and small ephrinA5 isoform (ephrinA5S). EphrinA5L is a putative tumor suppressor in several types of human cancers. However, the role of ephrinA5S in hepato-carcinogenesis remains unclear. In this study, we evaluate the role of ephrinA5 isoforms in human hepatocellular carcinomas (HCC).
A total of 142 paired HCCs and peritumoral liver tissue was examined for relative expression of ephrinA5L and ephrinA5S by using quantitative real-time polymerase chain reaction. We analyzed their expression in relation to clinical parameters, disease-free survival and overall survival. Functional assays were performed to dissect the possible underlying mechanisms. Both ephrinA5L and ephrinA5S were significantly downregulated in HCCs, as compared to those in peritumoral tissue (p = 0.013 and 0.001). Univariate analysis demonstrated that ephrinA5S was positively correlated with old age and histological grade. In multivariate analysis, high ephrinA5S expression in peritumoral tissue had better disease-free survival (p = 0.002) and overall survival (p = 0.045) in patients with HCC after surgical resection. Functional analysis in HCC cell lines revealed that ephrinA5S had a more potent suppressive effect than ephrinA5L on cell proliferation (p<0.05) and migration (p<0.01). Furthermore, forced expression of both ephrinA5 isoforms in HCC cell lines significantly down-regulated epidermal growth factor receptor (EGFR) expression by promoting c-Cbl-mediated EGFR degradation.
EphrinA5S might be a useful prognostic biomarker for HCCs after surgical resection. EphrinA5, especially ephrinA5S, acts as a tumor suppressor in hepatocarcinogenesis. Peritumoral small ephrinA5 isoform level could determine the postoperative survival in hepatocellular carcinoma.
PLoS ONE 01/2012; 7(7):e41749. · 4.09 Impact Factor
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Kun-Chun Chiang,
Chun-Nan Yeh,
Shin-Cheh Chen,
Shih-Che Shen,
Jun-Te Hsu, Ta-Sen Yeh,
Jong-Hwei S Pang,
Li-Jen Su,
Masashi Takano,
Atsushi Kittaka,
Horng-Heng Juang,
Tai C Chen
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ABSTRACT: Hormone antagonist therapy for estrogen receptor positive (ER+) breast cancer patients post radical surgery and radiation therapy has a poor prognosis and also causes bone loss. 1α,25-dihydroxyvitamin D(3) [1α,25(OH)(2)D(3)] is a potent antitumor agent in pre-clinical studies, but caused hypercalcemia when its effective antitumor doses were used. Therefore, we investigated the effects of a less-calcemic 1α,25(OH)(2)D(3) analog, 19-nor-2α-(3-hydroxypropyl)-1α,25-dihydroxyvitamin D(3 )(MART-10), on ER+MCF-7 cells. We demonstrate that MART-10 is 500- to 1000-fold more potent than 1α,25(OH)(2)D(3) in inhibiting cell growth in a dose- and time-dependent manner. MART-10 is also much more potent in arresting MCF-7cell cycle progression at G(0)/G(1) phase as compared to 1α,25(OH)(2)D(3), possibly mediated by a greater induction of p21 and p27 expression. Moreover, MART-10 is more active than 1α,25(OH)(2)D(3) in causing cell apoptosis, likely through a higher BAX/Bcl expression ratio and the subsequent cytochrome C release from mitochondria to cytosol. Based on our in vitro findings, MART-10 could be a promising vitamin D analog for the potential treatment of breast cancer, for example, ER+ patients, to decrease the tumor relapse rate and the side effect on bone caused by antihormone regimens. Thus, further in vivo animal study is warranted.
Evidence-based Complementary and Alternative Medicine 01/2012; 2012:310872. · 4.77 Impact Factor
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ABSTRACT: Opinions regarding the impact of human epidermal growth factor receptor (HER)-2 overexpression or HER-2 amplification on the prognosis of gastric cancer patients are mixed. The present study attempted to clarify this issue by investigating a large cohort of surgical patients.
We investigated 1,036 gastric cancer patients undergoing curative-intent resection. Their surgical specimens were evaluated for HER-2 expression by immunohistochemistry (IHC), and those with HER-2 expression levels of 2+ were additionally subjected to fluorescence in situ hybridization (FISH). Data on demographic and clinicopathological features and relevant prognostic factors in these patients were analyzed.
HER-2 positivity was noted in 64 (6.1%) of 1,036 gastric cancer patients, including 46 patients whose HER-2 expression level was 3+ on IHC and 18 patients whose FISH results were positive. On univariate analysis, HER-2 positivity was more often associated with differentiated histology, intestinal type, and negative resection margins, whereas only differentiated histology was independently associated with HER-2 positivity in a logistic regression model. For stage I-IV gastric cancer, HER-2 was not a prognostic factor. In a subpopulation study, although HER-2 positivity emerged as a favorable prognostic factor for stage III-IV gastric cancer on univariate analysis, it failed to be an independent prognostic factor after multivariate adjustment.
The prevalence of HER-2 positivity, determined using standardized assays and scoring criteria in a large cohort of gastric cancer patients after resection, was 6.1%. HER-2 positivity was phenotypically associated with differentiated histology. HER-2 is not an independent prognostic factor for gastric cancer.
The Oncologist 12/2011; 16(12):1706-13. · 3.91 Impact Factor
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ABSTRACT: Solid pseudopapillary neoplasm (SPN) is a distinct pancreatic neoplasm and has characteristic, aberrant nuclear expression of β-catenin in most cases. However, alterations in components of the Wnt pathway, other than the β-catenin (CTNNB1) gene mutation, have not been identified. In this study, we investigated the status of Axin-1, the spectrum of mutations in the CTNNB1 gene, and the clinicopathological features of SPNs.
We collected 27 SPNs from 25 patients. A tissue microarray was constructed to perform immunohistochemistry for β-catenin, E-cadherin, and Axin-1. The CTNNB1 and AXIN1 gene mutations were analyzed by DNA sequencing. Finally, the clinicopathological features of SPNs were analyzed for association with the CTNNB1 mutations and the Axin-1 alterations.
All 27 SPNs expressed nuclear immunoreactivity of β-catenin and exhibited a lack of membranous decoration of E-cadherin. All SPNs harbored CTNNB1 gene mutations. No alterations were present in the AXIN1 gene, and the immunohistochemical analysis revealed weak or absent reactivity of Axin-1 in the cytosol. All cases with a codon-37 CTNNB1 mutation had weak Axin-1 immunoreactivity in the cytoplasm (P = 0.018). No other significant correlation was found between clinicopathological parameters, CTNNB1 mutations, and Axin-1 alterations.
Nuclear β-catenin immunoexpression is characteristic for SPNs and corresponds to the CTNNB1 mutation. The Wnt pathway is involved in the tumorigenesis of SPNs, primarily through the alteration of β-catenin. Despite the absence of any identifiable genetic mutation, a low level of Axin-1 in the cytoplasm might contribute to the aberrant distribution of β-catenin in SPNs.
Annals of Surgical Oncology 07/2011; 19 Suppl 3:S438-46. · 4.17 Impact Factor
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Ta-Sen Yeh
Annals of Surgical Oncology 07/2011; · 4.17 Impact Factor
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ABSTRACT: The phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) is known to be an endogenous negative feedback or compensatory mechanism that serves to limit pro-inflammatory and chemotactic events in response to injury. The aim of this study is to elucidate whether Akt plays any role in 17β-estradiol (E2)-mediated attenuation of lung injury after acute pancreatitis (AP).
Male Sprague-Dawley rats underwent cerulein-induced AP. Rats were treated with vehicle (cyclodextrin), E2 (1 mg/kg body weight [BW]), or E2 plus PI3K/Akt inhibitor Wortmannin (100 μg/kg BW) 1h after the onset of AP. At 8 h after sham operation or AP, various parameters were measured.
AP led to a significant decrease in lung Akt phosphorylation, which was associated with increased lung tissue myeloperoxidase (MPO) activity, wet-to-dry weight ratios, interleukin (IL)-6, tumor necrosis factor (TNF)-α, cytokine-induced neutrophil chemoattractant (CINC)-1, and CINC-3 levels. Administration of E2 after AP restored the AP-induced decrease in Akt phosphorylation and attenuated the increase in lung injury markers (MPO activity and wet-to dry weight ratios) and pro-inflammatory mediator production. The effects of E2 on the lung were abolished by co-administration of Wortmannin.
These results collectively suggest evidences that the Akt pathway seems to be required for E2-mediated protection of lung injury after AP.
Injury 07/2011; 42(7):638-42. · 1.98 Impact Factor
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ABSTRACT: Since Rho-mediated signaling can regulate liver cancer cell proliferation, amino acid sequence changes of its downstream targets, actins, might alter the properties of cell growth. Here, we investigated the function of a novel class of actins, named κ-actins, in hepatocellular carcinoma (HCC).
Alexander cells overexpressing an HCC-derived κ-actin (Alex-κ cells) were established to study growth property changes. κ-actin expression was also determined in tumor and noncancerous tissues from 72 HCC patients. Survival analysis was conducted to evaluate the prognostic predictive value of κ-actin expression.
Phylogenetic analysis showed that κ-actin sequences constituted 94.7% and 17.6% of actin transcripts in Alex-κ and naive Alexander cells, respectively. Alex-κ cells exhibited serum-independent cell growth with increased anchorage-independent colony formation and BrdU incorporation upon serum deprivation. Cox proportional hazard analysis showed that κ-actin expression in both cancerous and noncancerous tissues predicted poorer postoperative disease-free survival (p=0.004).
Overexpression of κ-actin altered growth properties of hepatoma cells, contributing to poor postoperative prognosis.
Anticancer research 06/2011; 31(6):2037-44. · 1.73 Impact Factor
