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ABSTRACT: Cholangiocarcinoma (CCA) is a malignant neoplasm affecting thousands of individuals worldwide. CCA develops through a multistep process. In the current study, an oral thioacetamide (TAA)‑induced model of rat CCA was established which generates the histological progression of human CCA, particularly the mass‑forming type. Seven male Sprague‑Dawley rats were treated with TAA for 24 weeks to induce CCA. Following the generation of the rat CCA model, whole rat genomic oligo microarray was performed to examine gene expression profiles in CCA and non‑cancerous liver samples. In brief, 10,427 genes were found to be differentially expressed (8,318 upregulated and 3,489 downregulated) in CCA compared with non‑tumor liver tissue. The top 50 genes (upregulated or downregulated) were selected and their functional involvement in various pathways associated with cancer progression was analyzed, including cell proliferation, apoptosis, metabolism and the cell cycle. In addition, increased expression of CLCA3, COL1A2, DCN, GLIPr2 and NID1, and decreased expression of CYP2C7 and SLC10A1 were validated by quantitative real‑time PCR. Immunohistochemical analysis was performed to determine the protein expression levels of GLIPr2 and SLC10A1. The gene expression profiling performed in this study provides a unique opportunity for understanding the carcinogenesis of TAA‑induced CAA. In addition, expression profiling of a number of specific genes is likely to provide important novel biomarkers for the diagnosis of CCA and the development of novel therapeutic strategies for CCA.
Molecular Medicine Reports 06/2013; · 0.42 Impact Factor
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Journal of Clinical Oncology 04/2013; · 18.37 Impact Factor
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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: For many years, the understanding of gastrointestinal stromal tumors (GISTs), which are the most common mesenchymal tumors of the gastrointestinal tract, had been very limited. However, we are now able to provide a more precise definition through the use of pathology classification and molecular techniques. Coupled with the advancement of clinical practice, especially the development of targeted therapy, insight into GIST treatment has improved substantially. At present, organizations such as the National Comprehensive Cancer Network (NCCN) in the USA and the European Society for Medical Oncology (ESMO) have established consensus and drawn up guidelines for the diagnosis, treatment, and follow-up of GISTs. The Taiwan Surgical Society of Gastroenterology convened a group of multidisciplinary experts from across the country and drafted the first national GIST management guidelines in 2007 after a consensus meeting. Following subsequent treatment advances and the growing knowledge in tumor biology, the Taiwan Surgical Society of Gastroenterology experts have conducted a series of meetings to review newer evidence and made modifications to the original guidelines. We herein present the updated recommendations of the Taiwan Surgical Society of Gastroenterology for the diagnosis and treatment of GIST patients. We hope the guidelines can help enhance the quality of diagnosis, treatment and care of GIST patients in Taiwan.
World Journal of Surgical Oncology 11/2012; 10(1):246. · 1.12 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: 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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Kun-Chun Chiang,
Jim-Ray Chen,
Yu-Ting Huang,
Chen-Chen Huang, Chun-Nan Yeh,
Chien-Sheng Tsai,
Li-Wei Chen,
Hsien-Cin Chen,
Jun-Te Hsu,
Cheng-Hsu Wang,
Huang-Yang Chen
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ABSTRACT: Pancreatic cancer is a lethal disease without effective treatments at present. It ranks as s as 4th and 5th in cancer-related mortality in the western countries and worldwide. Locally advanced pancreatic duct carcinoma (PDAC) and metastatic PDAC, usually found the metastases over liver, peritoneum, or lung, have been shown to be with dismal prognosis. Brain metastasis is a rare entity and most cases reported before were found post-mortem. Intraductal papillary mucinous neoplasms of the pancreas (IPMN) has been deemed as a precursor of PDAC with very slow progression rate. Here we reported a case diagnosed with IPMN-derived PDAC with brain metastasis. After surgeries for PDAC and brain metastasis, subsequent chemotherapy and radiotherapy were also given. One and half year after surgery, this patient is still living with good performance status, which may warrant individualization of therapeutic strategy for PDAC with only brain metastasis.
World Journal of Surgical Oncology 07/2012; 10(1):138. · 1.12 Impact Factor
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Chueh-Chuan Yen, Chun-Nan Yeh,
Chi-Tung Cheng,
Shih-Ming Jung,
Shih-Chiang Huang,
Ting-Wei Chang,
Yi-Yin Jan,
Cheng-Hwai Tzeng,
Ta-Chung Chao,
Yeng-Yang Chen,
Ching-Yao Yang,
Ching-Liang Ho,
Jonathan A Fletcher
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ABSTRACT: For completely resected primary gastrointestinal stromal tumors (GISTs), mitotic rate, tumor size, and tumor location are important risk factors for recurrence. However, molecular markers for recurrence are still lacking.
We reanalyzed GIST gene expression profile GSE8167 available from the Gene Expression Omnibus (GEO) and confirmed the prognostic influence of one selected gene, aurora kinase A (AURKA), in another cohort of 142 patients using immunohistochemistry (IHC).
Thirty-two cases in GSE8167 were classified into two risk groups with distinct recurrence-free survival (RFS) and expression profiles using modified criteria of Miettinen et al. from the Armed Forces Institute of Pathology (AFIP-Miettinen). AURKA was among the 19 genes common to the top 50 features of the high-risk phenotype and a 67-gene signature called the complexity index in sarcomas. AURKA was significantly overexpressed in the high-risk group, and patients with high AURKA expression had significantly worse RFS than those with low expression. In the IHC-validated cohort, AURKA expression was significantly higher in nongastric tumors than in gastric tumors and was significantly correlated with AFIP-Miettinen risk group. Univariate analysis showed that RFS was significantly influenced by tumor size, mitotic count, AFIP-Miettinen risk group classification, and AURKA expression. However, only tumor size (P = 0.017), mitotic count (P = 0.007), and AURKA expression (P = 0.039) were identified as independent unfavorable prognostic factors for RFS in multivariate analysis.
By integrating bioinformatics and clinicopathological studies, AURKA was identified as a marker for high-risk GIST.
Annals of Surgical Oncology 05/2012; 19(11):3491-9. · 4.17 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: Liver angiosarcoma is a rare disease, however it still ranks as the third of most common primary liver maligancies. The prognosis of liver angiosarcoma is very poor with almost all patients with this kind of disease die within 2 years after diagnosis. No specific symptoms and signs are closely associated with this disease. Here, we report a case presenting shock status at first due to rupture of liver angiosarcoma- induced internal bleeding. After emergent transarterial embolization (TAE), she received partial hepatectomy two weeks later. 4 months after operation, she is still with a good performance status without obvious recurrence or metastasis identified.
World Journal of Surgical Oncology 01/2012; 10:23. · 1.12 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: Membrane-cytoskeleton linker organizer ezrin is a member of the ERM (ezrin-radixin-moesin) protein family. It has been suggested as an important element in the oncogenic process, particularly in conferring a metastatic ability on tumor cells. We hypothesized that the KIT oncogenic form is one of the proteins that modulates expression of the ezrin protein via phosphorylated ezrin at different residues; furthermore, it may interact with the protein merlin, and promoting tumor development via the PI3K or MAPK pathway. In the present study, we observed that differential expression of ezrin was a common feature in gastrointestinal stromal tumors (GISTs). We further demonstrated that cases exhibiting expression of phosphorylated Thr567 in the ezrin protein were associated with immunoactivities of KIT and merlin expression (p=0.039 and 0.013, respectively). In conclusion, GISTs harbor activation of KIT protein may induce phosphorylation of the downstream protein ezrin at certain residues, thereby triggering subsequent signal transduction cascades and driving downstream pathways of tumor progression. However, a larger series of tumor samples should be analyzed in future studies, as well as the identification of phosphorylated sites to determine the role of ezrin in tumor progression thus shedding light on clinical outcomes.
Molecular Medicine Reports 01/2012; 5(1):17-21. · 0.42 Impact Factor
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ABSTRACT: Computed tomography (CT) has been used in diagnosing acute appendicitis since late 1990s. Appropriate use of CT has not been studied prospectively in patients with suspected acute appendicitis and relative low Alvarado score.
Sixty participants with suspected acute appendicitis and an Alvarado score of 4 to 7 points were enrolled for analysis. Clinical and laboratory differences were compared between patients with histologically proven acute appendicitis (AA group) and patients without evidence of acute appendicitis (non-AA group) in the first part of the analysis. In the second part of the analysis, participants were divided into 2 groups: leukocytosis (LK group) and nonleukocytosis (non-LK group).
In the first phase of the analysis, there were statistically significant differences in white blood cell count (13.5 K vs 10.9 K per μL), neutrophilia (81.5% vs 73.5%), and hospital stay (4.9 vs 3.5 days) between the 2 groups. Disease spectrum between LK and non-LK groups was obtained in second part of analysis.
Computed tomography scan is necessary for patients with relatively low Alvarado score when leukocytosis is noted. In female patients without leukocytosis, further large-scale prospective studies are necessary to change the current diagnostic strategy.
The American journal of emergency medicine 12/2011; 30(8):1597-601. · 1.54 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: Our preliminary report of imatinib mesylate (IM) in gastrointestinal stromal tumor (GIST) patients detailed a high response rate; however, the long-term result is still unknown. We conducted an analysis of Taiwan advanced inoperable/metastatic GIST patients treated on IM regarding survival, pattern of failure, potential prognostic factors, and mutational status.
From 2001 to 2010, patients with pathologically proven advanced inoperable/metastatic GIST receiving IM were enrolled onto this study. Data on KIT mutational status, measurable tumor size, and other potential prognostic factors were prospectively collected. Patients were followed up for a median of 33.6 months.
There were 171 patients (106 men and 65 women) with response rate, and their clinical benefit for IM was 57.3% and 87.1%, respectively. Median progression-free survival (PFS) and overall survival (OS) for these 171 patients are 37.6 and 71.0 months, respectively. Of 171 patients, 120 (70.2%) remained on long-term IM use. Poor performance status, tumor larger than 11.5 cm, primary resistance, and the presence of an exon 9 mutation were independently associated with unfavorable PFS. Regarding OS, poor performance status, primary resistance, and tumor larger than 11.5 cm were three independently unfavorable predictors.
The median PFS and OS of 171 GIST patients are 37.6 and 71.0 months, respectively. Poor performance status, tumor size larger than 11.5 cm, primary resistance, and an exon 9 mutation were independently associated with unfavorable PFS. Regarding OS, poor performance status, primary resistance, and tumor size larger than 11.5 cm were three independent unfavorable predictors.
Translational oncology 12/2011; 4(6):328-35. · 3.40 Impact Factor
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ABSTRACT: The discovery that the active form of vitamin D, 1α,25-dihydroxyvitamin D [1α,25(OH)(2)D] can modulate cellular proliferation and differentiation of cancer cells has led to its potential application as a chemotherapeutic agent to treat a variety of cancers. However, the use of 1α,25(OH)(2)D is limited due to its lethal side effect of hypercalcemia upon systemic administration. To overcome this drawback, numerous analogs have been synthesized. In this report, we examined the anti-proliferative activity of a new analog, 19-nor-2α-(3-hydroxypropyl)-1α,25(OH)(2)D(3) (MART-10), in HepG2 liver cancer cells, and studied the potential mechanisms mediating this action. We found that MART-10 exhibited approximately 100-fold greater activity than 1α,25(OH)(2)D(3) in inhibiting HepG2 cell proliferation as determined by cell number counting method. MART-10 was also approximately 100-fold more potent than 1α,25(OH)(2)D(3) in the upregulation of p21 and p27, that in turn arrested HepG2 cells at the G(0)/G(1) phase to a greater extent. Given that no active caspase 3 was detected and treatment with 1α,25(OH)(2)D(3) or MART-10 did not further increase the fractions of apoptotic and necrosis cells over the controls, the growth-inhibitory effect of 1α,25(OH)(2)D(3) and MART-10 on HepG2 cells may not involve apoptosis. Overall, our findings suggest that MART-10 is a good candidate as a novel therapeutic regimen against liver cancer. Further pre-clinical studies using animal models and the subsequent human clinical trials are warranted.
Steroids 08/2011; 76(13):1513-9. · 2.83 Impact Factor
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ABSTRACT: Gastric adenocarcinoma (GC) occurs frequently in the sixth decade of life and is uncommon in patients aged 40 years or younger. The aims of this study were to define the clinicopathological features and elucidate the prognostic factors of GC in the young.
Between 1998 and 2006, 1,815 GC patients undergoing resection were enrolled in a prospective database. The findings for 115(6.0%) patients aged 40 years or younger were compared with those of 1,009 patients between 56 and 75 years old.
The group of young patients with GC included significantly more women than the group of old patients (60.0% vs. 37.0%, respectively); young patients also had more T4 lesions (73.9% vs. 61.6%), undifferentiated tumors (85.2% vs. 55.1%), severe desmoplasia (41.4%vs. 12.2%), Lauren’s diffuse-type cancers (55.6% vs. 27.7%), and perineural invasion (69.1% vs. 46.1%). Survival rates in younger patients at 3, 5, and 10 years after resection were 56.8%, 52.0%, and 42.1%, respectively, similar to those in older patients (P ¼ 0.411). Unfavorable independent prognostic factors of GC in the young were degree of nodal involvement (N3 vs. N0; P ¼ 0.001), advanced T status (T3–4 vs.T1–2; P ¼ 0.015), tumor size (>4 vs. ≤4 cm; P ¼ 0.019), and status of resection margins (positive vs. negative; P ¼ 0.044).
GC tends to exhibit more aggressive tumor behavior in young patients than in old patients; however, the surgical survival of young and old patients was similar. Advanced nodal involvement (N3) is the most important independent prognostic factor in the young.
Journal of Surgical Oncology 08/2011; 105(3):304-9. · 2.10 Impact Factor
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ABSTRACT: The non-classical actions of vitamin D, namely antiproliferation, pro-differentiation, pro-apoptosis, anti-inflammation, and immune regulation, have received great attention during the past decade. Increasing evidence from epidemiological studies showing the inverse association between vitamin D status and incidence of many forms of cancer as well as biochemical studies has suggested that vitamin D deficiency may play a role in the cause and progression of these types of cancer. Recently, vitamin D and its analogs have been deemed as potential regimen to treat a variety of cancers alone or in combination with other drugs. Although, the epidemiologic evidence regarding the association of vitamin D and hepatocellular carcinoma (HCC) is still inconclusive, biochemical evidence clearly indicates that HCC cells are responsive to the inhibitory effect of vitamin D and its analogs. In this review, we discuss the current status of HCC and its treatment, the source, metabolism, functions, and the mechanism of actions of vitamin D, and the biochemical studies of vitamin D analogs and their implications in the prevention and treatment of HCC.
Journal of Gastroenterology and Hepatology 08/2011; 26(11):1597-603. · 2.87 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: To characterize a culture model of rat CCA cells, which were derived from a transplantable TTA-induced CCA and designated as Chang Gung CCA (CGCCA).
The CGCCA cells were cultured at in vitro passage 12 times on a culture dish in DMEM medium. To measure the doubling time, 10(3) cells were plated in a 96-well plate containing the growth medium. The cells were harvested 4 to 10 d after seeding, and a standard MTT assay was used to measure the growth. The phenotype of CACCA cell and xenograft was determined by immunohistochemical study. We also determine the chromosomal alterations of CGCCA, G-banding and spectral karyotyping studies were performed. The CGCCA cell line was transplanted into the nude mice for examining its tumorigenicity. 2-Deoxy-2-((18)F)fluoro-D-glucose (FDG) autoradiography was also performed to evaluate the FDG uptake of the tumor xenograft.
The doubling time for the CGCCA cell line was 32 h. After transplantation into nude mice, FDG autoradiography showed that the tumors formed at the cell transplantation site had a latency period of 4-6 wk with high FDG uptake excluding necrosis tissue. Moreover, immunohistochemical staining revealed prominent cytoplasmic expression of c-erb-B2, CK19, c-Met, COX-II, EGFR, MUC4, and a negative expression of K-ras. All data confirmed the phenotypic features of the CGCCA cell line coincide with the xenograft mice tumors, indicating cells containing the tumorigenicity of CCA originated from CCA. In addition, karyotypic banding analysis showed that the diploid (2n) cell status combines with ring and giant rod marker chromosomes in these clones; either both types simultaneously appeared or only one type of marker chromosome in a pair appeared in a cell. The major materials contained in the marker chromosome were primarily identified from chromosome 4.
The current CGCCA cell line may be used as a non-K-ras effect CCA model and to obtain information and reveal novel pathways for CCA. Further applications regarding tumor markers or therapeutic targeting of CCA should be addressed accordingly.
World Journal of Gastroenterology 06/2011; 17(24):2924-32. · 2.47 Impact Factor
