• Asian Pacific Journal of Cancer Prevention
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• v.17 no.8
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• pp.3929-3937
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• 2016

Gastric cancer (GC) is a major health problem worldwide and is one of the ten most commonly diagnosed cancers in Jordan. GC is usually diagnosed at late aggressive stages in which treatment options are limited. Recently, heat shock proteins (HSPs) were found to be overexpressed in a wide range of malignancies have been considered as promising candidate biomarkers for GC. The aim of this study was to investigate pathogenic roles of a panel of cytosolic HSPs including HSP90, HSP70, HSP60 and HSP27 in GC. Immunohistochemistry was used to assess the level of expression of these proteins in archived tumor samples (N=87) representing various pathological characteristics of GC. HSP90, HSP60 and HSP27 were expressed abundantly in gastric tumors. On the other hand, HSP70 was reduced significantly and also found to be associated with Helicobacter pylori infection in tissues collected from GC patients. Furthermore, HSP27 was found to be associated with the level of differentiation. Our findings indicate a role of HSP70 as a potential prognostic biomarker, patients harboring positive HSP70 expression displaying worse disease free survival than those with negative HSP70 expression. Differential expression of HSPs may play crucial roles in the initiation and progression of GC, and could be exploited as future therapeutic targets.

• Journal of Ecology and Environment
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• v.38 no.3
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• pp.307-318
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• 2015

The objectives of this study were to identify multi-level stressors from blood biomarkers to community-level bioindicators and diagnose the stream ecosystem health in polluted streams. Blood chemistry such as total protein ($T_{Pro}$), blood urea nitrogen ($B_{UN}$), total cholesterol ($T_{Cho}$) and $A_{lb}$umin ($A_{lb}$) were analyzed from sentinel fish tissues; the functions of kidney, gill and liver were significantly decreased in the impacted zone ($I_z$), compared to the control zone ($C_z$). Histopathological analysis showed that fish liver tissues were normal in the $C_z$. Fish liver tissues in the $I_z$, however, showed large cell necrosis and degeneration and also had moderate lobular inflammation and inflammatory cell infiltration of lymphocytic histocytes. Species biotic index (SBI) at species level and stream health assessment (SHA) at community level indicated that chemical impacts were evident in the $I_z$ (ecological health; poor - very poor), and this was matched with the blood tissue analysis and histopathological analysis. The impairments of the streams were supported by water chemistry analysis (nitrogen, phosphorus). Tolerance guild analysis and trophic guild analysis of fish were showed significant differences (P < 0.01) between $C_z$ and $I_z$. Overall, multiple parameter analysis from biomarker level (blood tissues) to bioindicator level (community health) showed significantly greater impacts in the $I_z$ than $C_z$. This approach may be effective as a monitoring tool in identifying the multilateral and forthcoming problems related to chemical pollution and habitat degradation of stream ecosystems.

• Fisheries and Aquatic Sciences
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• v.12 no.4
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• pp.276-285
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• 2009

Despite great commercial interest, relatively little has been described about molecular mechanism of bivalve reproduction. We investigated genes involved in ovarian maturation of the Yesso scallop, Patinopecten yessoensis. GSI index and histological analysis revealed that maturation of ovary begin in February and spawning period is from April to June which is similar to the previous study in the East Sea. As result of combination analysis of differential display RTPCR (DDRT-PCR) and histological examination, vitellogenin (Vg), ferritin (Ft) and ADT/ATP carrier protein (ACC) were identified as differently expressed genes in maturating ovary. Endpoint RT-PCR results showed that Vg is ovary-specific genes whereas Ft and ACC are expressed ubiquitously suggesting that Vg can be good molecular markers for ovarian development and sex determination in bivalves. Quantitative PCR results revealed that Vg were expressed highest during growth stage and appears to play a major role in oocyte maturation. On the contrary, expression of Ft was highest after spawning stage, which suggests that up-regulation may be involved in spawning and inactive stages in which the scallops recover from spawning. In addition, high level of the mitochondrial gene, ACC, may play a role in energy metabolism in maturating oocytes. Isolation and molecular studies of these key genes will expand our knowledge of the physiological changes from various exogenous factors including temperature, salinity, pH, even or numerous endocrine disrupting chemicals (EDCs) during reproductive cycle. In addition, further study of these genes implicates various industrial applications including the stable seed production, increased food quality, or economic aquaculture system.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6423-6427
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• 2012

Background: Functional single nucleotide polymorphisms of x-ray repair cross-complementing protein 1 (XRCC1) have been suspected to contribute to uterine cervical cancer risk for a long time; however, most previous case-control studies were small sized and biased. Additionally, recent studies suggested that XRCC1 polymorphisms could be a biomarker of response to platinum-based chemotherapy. Methods: A comprehensive search was conducted to retrieve eligible studies and odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated to measure association strength. Results: A total of 13 studies were identified and analyzed. We found that the Arg194Trp polymorphism (Trp vs. Arg, OR=1.342, 95% CI: 1.176) was associated with increased risk of cervical cancer, while no significant association was found with Arg280His (His vs. Arg, OR=1.059, 95% CI: 0.863, 1.299) or Arg399Gln (Gln vs. Arg, OR=1.144, 95% CI: 0.938, 1.394). As for response to platinum-based chemotherapy, the variant XRCC1 399Gln allele (Gln vs. Arg, OR=0.345, 95% CI: 0.163, 0.729) was linked with a poor response; however, the Arg194Trp polymorphism (TrpArg vs. ArgArg, OR=6.421, 95% CI: 1.573, 26.205) predicted a good response. Conclusion: The Arg194Trp polymorphism of XRCC1 increases risk of cervical cancer; the variant 399Gln allele predicts poor response to platinum-based chemotherapy, while the Arg194Trp polymorphism indicates a good response.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.7
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• pp.4161-4165
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• 2013

Objective: To investigate discriminating protein patterns and potential biomarkers in serum samples between pre/postoperative pancreatic cancer patients and healthy controls. Methods: 23 serum samples from PC patients (12 preoperative and 11 postoperative) and 76 from healthy controls were analyzed using matrix-assisted laser desorption and ionization time-of-flight mass spectrometry (MALDI-TOF MS) technique combined with magnetic beads-based weak cation-exchange chromatography (MB-WCX). ClinProTools software selected several markers that made a distinction between pancreatic cancer patients and healthy controls. Results: 49 m/z distinctive peaks were found among the three groups, of which 33 significant peaks with a P < 0.001 were detected. Two proteins could distinguish the preoperative pancreatic cancer patients from the healthy controls. About 15 proteins may be potential biomarkers in assessment of pancreatic cancer resection. Conclusion: MB-MALDI-TOF-MS method could generate serum peptidome profiles of pancreatic cancer and provide a new approach to identify potential biomarkers for diagnosis and prognosis of this malignancy.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.5687-5690
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• 2015

Background: Factors predictive of survival have been identified in Western patients with metastatic clear cell renal cell carcinoma (mCCRCC) treated with sunitinib. Less is known, however, about factors predictive of survival in Japanese patients. This study evaluated factors prognostic of survival in Japanese patients with mCCRCC treated with first-line sunitinib. Materials and Methods: This retrospective study evaluated 46 consecutive Japanese mCCRCC patients treated with sunitinib as first line therapy. Clinical and biochemical markers associated with progression-free survival (PFS) were analyzed, with prognostic factors selected by uniand multivariate Cox regression analyses. Results: Univariate analysis showed that factors significantly associated with poor PFS included Memorial Sloan-Kettering Cancer Center poor risk scores, International Metastatic RCC Database Consortium poor risk and high (>0.5 mg/dl) serum C-reactive protein (CRP) concentrations (p<0.001 each). Multivariate analysis showed that high serum CRP was independently associated with poorer PFS (p=0.040). Six month disease control rate (complete response, partial response and stable disease) in response to sunitinib was significantly higher in patients with normal (${\leq}0.5mg/dl$) than elevated baseline CRP (p<0.001). Conclusions: CRP is a significant independent predictor of PFS for Japanese patients with mCCRCC treated with first-line sunitinib. Pretreatment CRP concentration may be a useful biomarker predicting response to sunitinib treatment.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.1789-1795
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• 2016

Background: Breast cancer is the commonest female cancer worldwide and its propensity to metastasize negatively impacts on therapeutic outcome. Several clinicopathological parameters with prognostic/predictive significance have been associated with metastatic suppressor expression levels. The role of metastatic suppressor gene (MSG) KiSS1 in breast cancer remains unclear. Our goal was to investigate the possible clinical significance of KiSS1 breast cancer. Materials and Methods: The study was conducted on 87 histologically proven cases of breast cancer and background normal tiisue. Quantitative reverse transcriptase polymerase chain reaction (qRT PCR) and immunohistochemistry (IHC) were used to investigate KiSS1 at gene and protein levels, respectively, for correlation with several patient characteristics including age, family history, hormonal receptor status, stage, tumor size, nodal involvement and metastatic manifestation and finally with median overall survival (OS). Results: Our study revealed (i) KiSS1 levels were generally elevated in breast cancer vs normal tissue (P < 0.05). (ii) however, a statistically significant lower expression of KiSS1 was observed in metastatic vs non metastatic cases (P = 0.04). (iii) KiSS1 levels strongly correlated with T,N,M category, histological grade and advanced stage (p<0.001) but not other studied parameters. (iv) Lastly, a significant correlation between expression of KiSS1 and median OS was found (P = 0.04). Conclusions: Conclusively, less elevated KiSS1 expression is a negative prognostic factor for OS, advancing tumor stage, axillary lymph node status, metastatic propensity and advancing grade of the breast cancer patient. Patients with negative KiSS1 expression may require a more intensive therapeutic strategy.

• Journal of Nutrition and Health
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• v.35 no.5
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• pp.505-511
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• 2002

The study was designed to compare the anti-carcinogenic effect of different level of conjugated linoleic acid (CLA) in 1,2-dimethylhydrazine (DMH)-treated rats by determining biomarkers (apoptosis, cell proliferation, eicosanoids, 1,2-diacylglycerol) and phospholipid fatty acid profile in colonic mucosa. Eighty male Sprague Dawley rats weighing 180-220g were randomly divided into 4 groups depending on the content of CLA, i.e. 0.0% CLA, 0.5% CLA, 1.0% CLA, 1.5% CLA. The experimental diet contained protein 21.6%, carbohydrate 54.6%, and fat 14.5% including CLA mixture at different level by weight. The experimental diet was fed for 14 weeks with the initiation of intramuscular injection of DMH, which was injected twice a week for 6 weeks to give total amount of 180 mg/kg body weight. Regardless of the amount of CLA supplemented to diet, CLA significantly increased the apoptotic index but did not have significant effect on cell proliferation in colonic mucosa. CLA was undetected in colonic mucosal phospholipid of rats fed the 0% CLA diet and increased to 5.9mg/g phospholipid in rats fed the 0.5% diet. The apoptotic index was increased by 251% and the 1,2-DAG content was decreased by 57% in rats fed 0.5% CLA. No further changes in these variables were observed when CLA in the diet was raised to 1.0% or 1.5%. However, dietary CLA decreased mucosal levels of prostaglandin (PG)E$_2$, thromboxane (TX)B$_2$, and arachidonic acid in dose-dependent manner. The present data indicate that dietary CLA can inhibit DMH-induced colon carcinogenesis by mechanism probably involving increased apoptosis.

• Mass Spectrometry Letters
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• v.5 no.1
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• pp.16-23
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• 2014

Liquid chromatography based mass spectrometry (LC-MS) is a key technology for analyzing highly complex and dynamic proteome samples. With highly accurate and sensitive LC-MS analysis of complex proteome samples, efficient data processing is another critical issue to obtain more information from LC-MS data. A typical proteomic data processing starts with protein database search engine which assigns peptide sequences to MS/MS spectra and finds proteins. Although several search engines, such as SEQUEST and MASCOT, have been widely used, there is no unique standard way to interpret MS/MS spectra of peptides. Each search engine has pros and cons depending on types of mass spectrometers and physicochemical properties of peptides. In this study, we describe a novel data process pipeline which identifies more peptides and proteins by correcting precursor ion mass numbers and unifying multi search engines results. The pipeline utilizes two open-source software, iPE-MMR for mass number correction, and iProphet to combine several search results. The integrated pipeline identified 25% more proteins in mouse epididymal adipose tissue compared with the conventional method. Also the pipeline was validated using control and colitis induced colon tissue. The results of the present study shows that the integrated pipeline can efficiently identify increased number of proteins compared to the conventional method which can be a breakthrough in identification of a potential biomarker candidate.

• Genomics & Informatics
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• v.2 no.2
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• pp.75-80
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• 2004

In a variety of animal species, the perinatal exposure of experimental animals to the 2,3,7,8-tetrachlorodibenzo­p-dioxin (TCDD) leads to the immune dysfunction, which is more severe and persistent than that caused by adult exposure. We report here the changes of gene expression and the identification of the marker-genes representing the dioxin exposure. The expressions of the transcripts were analyzed using the 11 K oligonucleotide­microarray from the bone marrow cells of male C57BL/6J mice after an intraperitoneal injection of $1{\mu}g$ TCDD/kg body weight at various time intervals: gestational 6.5 day(G6.5), 13.5 day(G13.5), 18.5 day(G18.5), and postnatal 3 (P3W)and 6 week (P6W). The type of self-organizing maps(SOM) representing the specific exposure dioxin could be identified as follows; G6.5D(C14), G13.5D(C0, C5, C10, C18), G18.5D(7): P3W(C2, C21), and P6W(C4, C15, C20). The candidate marker-genes were restricted to the transcripts, which could be consistently expressed greater than $\pm$2-fold in three experiments. The resulting candidates were 85 genes, the characteristics of that were involved in cell physiology and cell functions such as cell proliferation and immune function. We identified the biomarker-genes for dioxin exposure: smc -like 2 from SOM C14 for the dioxin exposure at G6.5D, focal adhesion kinase and 6 other genes from C0, and protein tyrosine phosphatase 4a2 and 3 other genes from C5 for G13.5D, platelet factor 4 from C7 for G18.5D, fos from C2 for P3W.