• Macromolecular Research
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• 제13권3호
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• pp.167-175
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• 2005

This review explores recent works involving the use of the self-assembled nanoparticles of bile acid-modified glycol chitosans (BGCs) as a new drug carrier for cancer therapy. BGC nanoparticles were produced by chemically grafting different bile acids through the use of l-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC). The precise control of the size, structure, and hydrophobicity of the various BGC nanoparticles could be achieved by grafting different amounts of bile acids. The BGC nanoparticles so produced formed nanoparticles ranging in size from 210 to 850 nm in phosphate-buffered saline (PBS, pH=7.4), which exhibited substantially lower critical aggregation concentrations (0.038-0.260 mg/mL) than those of other low-molecular-weight surfactants, indicating that they possess high thermodynamic stability. The SOC nanoparticles could encapsulate small molecular peptides and hydrophobic anticancer drugs with a high loading efficiency and release them in a sustained manner. This review also highlights the biodistribution of the BGC nanoparticles, in order to demonstrate their accumulation in the tumor tissue, by utilizing the enhanced permeability and retention (EPR) effect. The different approaches used to optimize the delivery of drugs to treat cancer are also described in the last section.

• 응용통계연구
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• 제24권5호
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• pp.847-859
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• 2011

cDNA microarray-based comparative genomic hybridization(CGH) data includes low-intensity spots and thus a statistical strategy is needed to detect subtle differences between different cancer classes. In this study, genes displaying a high frequency of alteration in one of the different classes were selected among the pre-selected genes that show relatively large variations between genes compared to total variations. Utilizing copy-number changes of the selected genes, this study suggests a statistical approach to predict patients' classes with increased performance by pre-classifying patients with similar genetic alteration scores. Two-stage logistic regression model(TLRM) was suggested to pre-classify homogeneous patients and predict patients' classes for cancer prediction; a decision tree(DT) was combined with logistic regression on the set of informative genes. TLRM was constructed in cDNA microarray-based CGH data from the Cancer Metastasis Research Center(CMRC) at Yonsei University; it predicted the patients' clinical diagnoses with perfect matches (except for one patient among the high-risk and low-risk classified patients where the performance of predictions is critical due to the high sensitivity and specificity requirements for clinical treatments. Accuracy validated by leave-one-out cross-validation(LOOCV) was 83.3% while other classification methods of CART and DT performed as comparisons showed worse performances than TLRM.

• Journal of Gastric Cancer
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• 제13권3호
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• pp.129-135
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• 2013

Gastric cancer is the second leading cause of cancer-related deaths worldwide. In advanced and metastatic gastric cancer, the conventional chemotherapy with limited efficacy shows an overall survival period of about 10 months. Patient specific and effective treatments known as personalized cancer therapy is of significant importance. Advances in high-throughput technologies such as microarray and next generation sequencing for genes, protein expression profiles and oncogenic signaling pathways have reinforced the discovery of treatment targets and personalized treatments. However, there are numerous challenges from cancer target discoveries to practical clinical benefits. Although there is a flood of biomarkers and target agents, only a minority of patients are tested and treated accordingly. Numerous molecular target agents have been under investigation for gastric cancer. Currently, targets for gastric cancer include the epidermal growth factor receptor family, mesenchymal-epithelial transition factor axis, and the phosphatidylinositol 3-kinase-AKT-mammalian target of rapamycin pathways. Deeper insights of molecular characteristics for gastric cancer has enabled the molecular classification of gastric cancer, the diagnosis of gastric cancer, the prediction of prognosis, the recognition of gastric cancer driver genes, and the discovery of potential therapeutic targets. Not only have we deeper insights for the molecular diversity of gastric cancer, but we have also prospected both affirmative potentials and hurdles to molecular diagnostics. New paradigm of transdisciplinary team science, which is composed of innovative explorations and clinical investigations of oncologists, geneticists, pathologists, biologists, and bio-informaticians, is mandatory to recognize personalized target therapy.

• Asian Pacific Journal of Cancer Prevention
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• 제13권6호
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• pp.2639-2642
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• 2012

Background: The patterns of gastric cancer recurrence vary across societies. We designed the current study in an attempt to evaluate and reveal the outbreak of the recurrence patterns of gastric cancer and also prediction of time to recurrence and its effected factors in Iran. Materials and Methods: This research was performed from March 2003 to February 2007. Demographic characteristics, clinical and pathological diagnosis and classification including pathologic stage, tumor grade, tumor site and tumor size in of patients with GC recurrent were collected from patients' data files. To evaluate of factors affected on the relapse of the GC patients, gender, age at diagnosis, treatment type and Hgb were included in the research. Data were analyzed using Kaplan-Meier and logistic regression models. Results: After treatment, 82 patients suffered recurrence, 42, 33 and 17 by the ends of first, second and third years. The mean ( SD) and median ( IQR) time to recurrence in patients with GC were 25.5 (20.6-30.1) and 21.5 (15.6-27.1) months, respectively. The results of multivariate analysis logistic regression showed that only pathologic stage, tumor grade and tumor site significantly affected the recurrence. Conclusions: We found that pathologic stage, tumor grade and tumor site significantly affect on the recurrence of GC which has a high positive prognostic value and might be functional for better follow-up and selecting the patients at risk. We also showed time to recurrence to be an important factor for follow-up of patients.

• Asian Pacific Journal of Cancer Prevention
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• 제15권3호
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• pp.1481-1488
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• 2014

Background: To avoid performing axillary lymph node dissection (ALND) for non-sentinel lymph node (SLN)-negative patients with-SLN positive axilla, nomograms for predicting the status have been developed in many centers. We created a new nomogram predicting non-SLN metastasis in SLN-positive patients with invasive breast cancer and evaluated 14 existing breast cancer models in our patient group. Materials and Methods: Two hundred and thirty seven invasive breast cancer patients with SLN metastases who underwent ALND were included in the study. Based on independent predictive factors for non-SLN metastasis identified by logistic regression analysis, we developed a new nomogram. Receiver operating characteristics (ROC) curves for the models were created and the areas under the curves (AUC) were computed. Results: In a multivariate analysis, tumor size, presence of lymphovascular invasion, extranodal extension of SLN, large size of metastatic SLN, the number of negative SLNs, and multifocality were found to be independent predictive factors for non-SLN metastasis. The AUC was found to be 0.87, and calibration was good for the present Ondokuz Mayis nomogram. Among the 14 validated models, the MSKCC, Stanford, Turkish, MD Anderson, MOU (Masaryk), Ljubljana, and DEU models yielded excellent AUC values of > 0.80. Conclusions: We present a new model to predict the likelihood of non-SLN metastasis. Each clinic should determine and use the most suitable nomogram or should create their own nomograms for the prediction of non- SLN metastasis.

• Asian Pacific Journal of Cancer Prevention
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• 제14권8호
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• pp.4847-4851
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• 2013

Objectives: To evaluate accuracy of FDG-PET CT in prediction of persistent disease in head and neck cancer cases and to determine prognostic value of metabolic tumor response. Materials and Methods: Between 2009 and 2011, 46 patients with squamous cell carcinoma of head and neck receiving PET-CT were treated with definitive radiotherapy, with or without chemotherapy. There were 29 nasopharyngeal, 11 hypopharyngeal, 3 oropharyngeal and 3 laryngeal cancer patients, with a median age of 50.5 years (range 16-84), 32 males and 14 females. All patients were evaluated with PET-CT median 3-5 months (2.4-9.4) after completion of radiotherapy. Results: After a median 20 months of follow up, complete metabolic response was observed in 63% of patients. Suspicious residual uptake was present in 10.9% and residual metabolic uptake in 26.0% of patients. The overall sensitivity, specificity, positive predictive value and negative predictive value of FDG-PET-CT for detection of residual disease was 91% and 81%, 64% and 96% respectively. Two year LRC was 95% in complete responders while it was 34% in non-complete responders. Conclusions: FDG PET CT is a valuable tool for assessment of treatment response, especially in patients at high risk of local recurrence, and also as an indicator of prognosis. Definitely more precise criteria are required for assessment of response, there being no clear cut uptake value indicating residual disease. Futhermore, repair processes of normal tissue may consume glucose which appear as increased uptake in control FDG PET CT.

• Asian Pacific Journal of Cancer Prevention
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• 제15권2호
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• pp.937-943
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• 2014

Polymorphisms in miRNA binding sites have been shown to affect miRNA binding to target genes, resulting in differential mRNA and protein expression and susceptibility to common diseases. Our purpose was to predict SNPs (single nucleotide polymorphisms) within miRNA binding sites of inflammatory genes in relation to gastric cancer. A complete list of SNPs in the 3'UTR regions of all inflammatory genes associated with gastric cancer was obtained from Pubmed. miRNA target prediction databases (MirSNP, Targetscan Human 6.2, PolymiRTS 3.0, miRNASNP 2.0, and Patrocles) were used to predict miRNA target sites. There were 99 SNPs with MAF>0.05 within the miRNA binding sites of 41 genes among 72 inflammation-related genes associated with gastric cancer. NF-${\kappa}B$ and JAK-STAT are the two most important signaling pathways. 47 SNPs of 25 genes with 95 miRNAs were predicted. CCL2 and IL1F5 were found to be the shared target genes of hsa-miRNA-624-3p. Bioinformatic methods could identify a set of SNPs within miRNA binding sites of inflammatory genes, and provide data and direction for subsequent functional verification research.

• Experimental and Molecular Medicine
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• 제50권11호
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• pp.7.1-7.12
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• 2018

Recent findings from The Cancer Genome Atlas project have provided a comprehensive map of genomic alterations that occur in hepatocellular carcinoma (HCC), including unexpected mutations in apolipoprotein B (APOB). We aimed to determine the clinical significance of this non-oncogenetic mutation in HCC. An Apob gene signature was derived from genes that differed between control mice and mice treated with siRNA specific for Apob (1.5-fold difference; P < 0.005). Human gene expression data were collected from four independent HCC cohorts (n = 941). A prediction model was constructed using Bayesian compound covariate prediction, and the robustness of the APOB gene signature was validated in HCC cohorts. The correlation of the APOB signature with previously validated gene signatures was performed, and network analysis was conducted using ingenuity pathway analysis. APOB inactivation was associated with poor prognosis when the APOB gene signature was applied in all human HCC cohorts. Poor prognosis with APOB inactivation was consistently observed through cross-validation with previously reported gene signatures (NCIP A, HS, high-recurrence SNUR, and high RS subtypes). Knowledge-based gene network analysis using genes that differed between low-APOB and high-APOB groups in all four cohorts revealed that low-APOB activity was associated with upregulation of oncogenic and metastatic regulators, such as HGF, MTIF, ERBB2, FOXM1, and CD44, and inhibition of tumor suppressors, such as TP53 and PTEN. In conclusion, APOB inactivation is associated with poor outcome in patients with HCC, and APOB may play a role in regulating multiple genes involved in HCC development.

• 대한의용생체공학회:의공학회지
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• 제38권5호
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• pp.271-276
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• 2017

Cancer biomarkers are using in the diagnosis, staging, prognosis and prediction of disease progression. But, there are not sufficiently profiled and validated in early detection and risk classification of prostate cancer. In this study, we have devoted to finding a panel of serum biomarkers that are able to detect the diagnosis of prostate cancer. The serum samples were consisted of 111 prostate cancer and 343 control samples and examined. Eleven biomarkers were constructed in this study, and then nine biomarkers were relevant to candidate biomarkers by using t test. Finally, four biomarkers, PSA, ApoA2, CYFRA21.1 and TTR, were selected as the prostate cancer biomarker panel, logistic regression was used to identify algorithms for diagnostic biomarker combinations(AUC = 0.9697). A panel of combination biomarkers is less invasive and could supplement clinical diagnostic accuracy.

• Asian Pacific Journal of Cancer Prevention
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• 제17권4호
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• pp.2199-2203
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• 2016

One of the most common cancer types faced by the women around the world is breast cancer. Among the several low, moderate and high penetrance genes conferring susceptibility to breast cancer, PTEN is one which is known to be mutated in many tumor types. In this study, we predicted and analyzed the impact of three deleterious coding non-synonymous single nucleotide polymorphisms rs121909218 (G129E), rs121909229 (R130Q) and rs57374291 (D107N) in the PTEN gene on the phenotype of breast tumors using computational tools SIFT, Polyphen-2, PROVEAN, MUPro, POPMusic and the GETAREA server.