• Smart Structures and Systems
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• v.8 no.1
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• pp.17-37
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• 2011

The microcantilever (MCL) sensor is one of the most promising platforms for next-generation label-free biosensing applications. It outperforms conventional label-free detection methods in terms of portability and parallelization. In this paper, an overview of recent advances in our understanding of the coupling between biomolecular interactions and MCL responses is given. A dual compact optical MCL sensing platform was built to enable biosensing experiments both in gas-phase environments and in solutions. The thermal bimorph effect was found to be an effective nanomanipulator for the MCL platform calibration. The study of the alkanethiol self-assembly monolayer (SAM) chain length effect revealed that 1-octanethiol ($C_8H_{17}SH$) induced a larger deflection than that from 1-dodecanethiol ($C_{12}H_{25}SH$) in solutions. Using the clinically relevant biomarker C-reactive protein (CRP), we revealed that the analytical sensitivity of the MCL reached a diagnostic level of $1{\sim}500{\mu}g/ml$ within a 7% coefficient of variation. Using grazing incident x-ray diffractometer (GIXRD) analysis, we found that the gold surface was dominated by the (111) crystalline plane. Moreover, using X-ray photoelectron spectroscopy (XPS) analysis, we confirmed that the Au-S covalent bonds occurred in SAM adsorption whereas CRP molecular bindings occurred in protein analysis. First principles density functional theory (DFT) simulations were also used to examine biomolecular adsorption mechanisms. Multiscale modeling was then developed to connect the interactions at the molecular level with the MCL mechanical response. The alkanethiol SAM chain length effect in air was successfully predicted using the multiscale scheme.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.22
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• pp.9927-9931
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• 2014

The objectives of this study were to examine serum periplakin expression in patients with urothelial carcinoma of the urinary bladder and in normal controls, and to examine relationships with clinicopathological findings. Detection of serum periplakin was performed in 50 patients and 30 normal controls with anti-periplakin antibodies using the automatic dot blot system, and a micro-dot blot array with a 256 solid-pin system. Levels in patients with urothelial carcinoma of the urinary bladder were significantly lower than those in normal controls (0.31 and 5.68, respectively; p<0.0001). The area under the receiver-operator curve level for urothelial carcinoma of the urinary bladder was 0.845. The sensitivity and specificity, using a cut-off point of 4.045, were 83.7% and 73.3%, respectively. In addition, serum periplakin levels were significantly higher in patients with muscle-invasive cancer than in those with nonmuscle-invasive cancer (P = 0.03). In multivariate Cox proportional hazards regression analysis, none of the clinicopathological factors was associated with an increased risk for progression and cancer-specific survival. Examination of the serum periplakin level may play a role as a non-invasive diagnostic modality to aid urine cytology and cystoscopy.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7149-7154
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• 2013

Objective: Increasing scientific evidence suggests that common variants in the PALB2 gene may confer susceptibility to breast cancer, but many studies have yielded inconclusive results. This meta-analysis aimed to derive a more precise estimation of the relationship between PALB2 genetic variants and breast cancer risk. Methods: An extensive literary search for relevant studies was conducted in PubMed, Embase, Web of Science, Cochrane Library, CISCOM, CINAHL, Google Scholar, CNKI and CBM databases from their inception through September 1st, 2013. A meta-analysis was performed using the STATA 12.0 software and crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Results: Six case-control studies were included with a total of 4,499 breast cancer cases and 6,369 healthy controls. Our meta-analysis reveals that PALB2 genetic variants may increase the risk of breast cancer (allele model: OR>1.36, 95%CI: 1.20~1.52, P < 0.001; dominant model: OR>1.64, 95%CI: 1.42~1.91, P < 0.001; respectively). Subgroup analyses by ethnicity indicated PALB2 genetic variants were associated with an increased risk of breast cancer among both Caucasian and Asian populations (all P < 0.05). No publication bias was detected in this meta-analysis (all P > 0.05). Conclusion: The current meta-analysis indicates that PALB2 genetic variants may increase the risk of breast cancer. Thus, detection of PALB2 genetic variants may be a promising biomarker approach.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.21
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• pp.9283-9289
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• 2014

Background: Acute lymphoblastic leukemia (ALL) is the most common cancer diagnosed in children and represents approximately 25% of cancer diagnoses among those younger than 15 years of age. Materials and Methods: This study investigated alterations in the displacement loop (d-loop) region of mitochondrial DNA (mtDNA) as a risk factor and diagnostic biomarker for early detection and diagnosis of acute lymphoblastic leukemia. Using mtDNA from 23 subjects diagnosed with acute lymphoblastic leukemia, the first 450 bp of the d-loop region were amplified and successfully sequenced. Results: This revealed 132 mutations at 25 positions in this region, with a mean of 6 alterations per subject. The d-loop alterations in mtDNA in subjects were all identified as single nucleotide polymorphisms in a homoplasmic distribution pattern. Mutant alleles were observed in all subjects with individual frequency rates of up to 95%. Thirteen mutant alleles in the d-loop region of mtDNA occurred with a high frequency. Novel alleles and locations were also identified in the d-loop of mtDNA as follows: 89 G insertions (40%), 95 G insertions (13%), 182 C/T substitutions (5%), 308 C insertions (19%), and 311 C insertions (80%). The findings of this study need to be replicated to be confirmed. Conclusions: Further investigation of the relationship between mutations in mitochondrial d-loop genes and incidence of acute lymphoblastic leukemia is recommended.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.2
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• pp.753-756
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• 2015

Background: Red cell distribution width (RDW) is one of the standard parameters with blood cell counts. Much previous research has indicated that it increases in cases of systemic inflammation or cardiametabolic incident. However, information on the relation of RDW with solid tumors causing systemic inflammation is limited. In the present research, we examined the relation of RDW with malignant and benign lesions of the colon. Materials and Methods: 115 patients with colon polyps (group 1), and 30 with colon cancer (group 2) who were diagnosed histopathologically in our clinic between January 2010-January 2013 were scanned retrospectively. Patients with anemia, hematologic diseases and active inflammation were excluded. RDW, mean corpuscular volume (MCV), hemoglobin (Hgb) and platelet (Plt) measurements were recorded and their relations with the malignant and benign lesions of the colon were examined. Results: Both groups were similar in age and gender distribution. RDW values of patients with colon cancer were significantly higher than the patients with colon polyp (p=0,01). No significant differences were detected between the two groups in terms of MCV and Plt values (p>0,05). Conclusions: RDW can be used as an early warning biomarker for solid colon tumors. Further prospective research is required on the relations of cheap and easily measured RDW parameters with colon malignancies.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6039-6045
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• 2012

This study was conducted to assess the predictive value of p-glycoprotein (p-gp) and p53 immunoexpression in human papillomavirus (HPV) infected cases of cervical dysplasia. Expression of both p-gp and p53 proteins was detected in cervical smears from 177 squamous intraepithelial lesions (SIL) cases along with 183 "atypical squamous cells of unknown significance" (ASCUS) and 150 normal cases. HPV 16 and 18 infection was detected by polymerase chain reaction using type-specific primers for HPV sub-types. There were no significant detectable p53 and p-gp expression in the normal cervix smears (p>0.05). In the ASCUS group 10 cases were positive for both p53 and p-gp immunoreactivity. In cervical dysplasia cases, p53 was positive in 86 (48.58%) while p-gp was positive in 93 (52.54%) and the two markers showed a highly significant correlation (r=0.92, p<0.001). Expression of p53 and p-gp was associated with grade of SIL (p<0.001). A positive correlation between the presence of HPV and expression of proteins p53 and p-gp in smears of patients with cervical lesions was also noted (p<0.001). Thus, p53 and p-gp immunostaining in cervical smears may act as an auxiliary biomarker for detection of HPV-associated cervical lesions. Additionally, a significant positive correlation between ascending grades of SIL and labeling indices of markers suggests that p53 and p-gp can be used as an adjunct to cytomorphological interpretation of conventional cervical Pap smears.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.4
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• pp.1563-1567
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• 2012

To investigate the relationship between serum miRNA-21 (miR-21) expression in esophageal squamous cell carcinomas (ESCCs) and its clinicopathologic features, a 1:1 matched case-control study including 21 patients with ESCC and 21 age- and gender-matched healthy controls was carried out. Serum specimens were taken from all subjects. Total RNA was extracted and the stem-loop real time polymerase chain reaction was used to measure serum miR-21 in both groups. Clinical parameters were assessed to determine associations with serum miR-21 concentrations. Serum miR-21 expression in ESCC samples was significantly higher than in paired cancer-free samples (P<0.05). Metastasis was associated with mir-21 expression in serum (P<0.05), ESCC patients with metastasis having 8.4-fold higher serum miR-21 concentrations than healthy controls. There were no statistically significant associations between miR-21 expression and clinicopathologic parameters, such as gender (P>0.05), age (P>0.05), tumor location (P>0.05), cell differentiation (P>0.05), TNM staging (P>0.05), whether chemo/radiotherapy had been administered (P>0.05), or whether surgery had been performed (P>0.05). These findings suggest that the detection of microRNA-21 in serum might serve as a new tumor biomarker in diagnosis and assessment of prognosis of ESCCs.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.7
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• pp.4261-4265
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• 2013

Increasing scientific evidence suggests that ribonucleotide reductase M1 (RRM1) may be a powerful predictor of survival in patients with pancreatic cancer treated with adjuvant gemcitabine-based chemotherapy after operative resection, but many existing studies have yielded inconclusive results. This meta-analysis aimed to assess the prognostic role of RRM1 in predicting survival in patients with pancreatic cancer treated with gemcitabine. An extensive literature search for relevant studies was conducted on PubMed, Embase, Web of Science, Cochrane Library, and CBM databases from their inception through May 1st, 2013. This meta-analysis was performed using the STATA 12.0 software and crude hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated. Eight clinical studies were included in this meta-analysis with a total of 665 pancreatic cancer patients treated with adjuvant gemcitabine-based chemotherapy, including 373 patients in the high RRM1 expression group and 292 patients in the low RRM1 expression group. Our meta-analysis revealed that high RRM1 expression was associated with improved overall survival (OS) of pancreatic cancer patients (HR=1.56, 95%CI=0.95-2.17, P<0.001). High RRM1 expression also was linked to longer disease-free survival (DFS) than low RRM1 expression (HR=1.37, 95%CI=0.25-2.48, P=0.016). In conclusion, our meta-analysis suggests that high RRM1 expression may be associated with improved OS and DFS of pancreatic cancer patients treated with adjuvant gemcitabine-based chemotherapy. Detection of RRM1 expression may be a promising biomarker for gemcitabine response and prognosis in pancreatic cancer patients.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.15
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• pp.6121-6125
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• 2014

Background: Prostate-specific antigen (PSA) is a potential biomarker for early detection of prostate cancer (PCa) but its level is known to be affected by many background factors and roles of ubiquitous toxicants have not been determined. Endocrine disrupting chemicals (EDCs) are ubiquitous reproductive toxicants used in consumer products, which promote tumor formation in some reproductive model systems by binding to AhR, but human data on its expression in prostate cancer as well as its association with PSA levels are not clear. This study aimed to evaluate the expression levels of AhR and its association with serological levels of PSA and to detect possible effects of background factors and EDC exposure history on PSA levels in PCa cases. Materials and Methods: A cross-sectional study was conducted on the tissue levels of AhR and serum levels of PSA in 53 PCa cases from 2008-2011 and associations between each and background and lifestyle related factors were determined. Results: Although the AhR was overexpressed in PCa and correlated with the age of patients, it did not correlate with PSA levels.Of nutritional factors, increased intake of polysaturated fats and fish in the routine regimen of PCa cases increased the PSA levels significantly. Conclusions: AhR overexpression in PCa pontws to roles of EDCs in PCa but without any direct association with PSA levels. However, PSA levels are affected by exposure to possible toxicants in foods whichneed to be assessed as possible risk factors of PCa in future studies.

• Analytical Science and Technology
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• v.28 no.1
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• pp.1-7
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• 2015

4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a tobacco specific nitrosamine found only in tobacco products. The ability to monitor biomarker concentrations is very important in understanding environmental tobacco smoke (ETS). In this study, an efficient and sensitive method for the analysis of NNK in dust was developed and validated using liquid chromatography tandem mass spectrometry. Dust was collected with filter paper soaked in methanol. The standard solution and dust sample were diluted with 100 mM ammonium acetate and extracted using dichloromethane. Our calibration curves ranged from 25 to $10^4pg/mL$. Excellent linearity was obtained with correlation coefficient values between 0.9996 and 1.0000. The limit of detection (LOD) was 5 pg/mL ($S/N{\geq}3$) and the retention time was 10 min. The limit of quantification (LOQ) was 25 pg/mL, and the acceptance criteria was the rate of 98-103% (80-120% at levels up to $3{\times}LOQ$). The coefficient of variations (CV) was 2.8%. Accuracies determined from dust samples spiked with four different levels of NNK racurves ranged that from 25 to 104 pg/mL. Excellent linearity was obtained between 92.1% and 114%. The precision of the method was acceptable (5% of CV). The recovery rates of the whole analytical procedure at low, medium, and high levels were 105.7-116.5% for NNK. The carry-over effects during LC-MS/MS analysis were not observed for NNK. This manuscript summarizes the scientific evidence on the use of markers to measure ETS.