• Nutrition Research and Practice
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• v.16 no.2
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• pp.161-172
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• 2022

BACKGROUND/OBJECTIVES: Colorectal cancer (CRC) is the third most common cancer worldwide and has a high recurrence rate, which is associated with cancer stem cells (CSCs). β-carotene (BC) possesses antioxidant activity and several anticancer mechanisms. However, no investigation has examined its effect on colon cancer stemness. MATERIALS/METHODS: CD133⁺CD44⁺ HCT116 and CD133⁺CD44⁺ HT-29 cells were isolated and analyzed their self-renewal capacity by clonogenic and sphere formation assays. Expressions of several CSCs markers and Wnt/β-catenin signaling were examined. In addition, CD133⁺CD44⁺ HCT116 cells were subcutaneously injected in xenograft mice and analyzed the effect of BC on tumor formation, tumor volume, and CSCs markers in tumors. RESULTS: BC inhibited self-renewal capacity and CSC markers, including CD44, CD133, ALDH1A1, NOTCH1, Sox2, and β-catenin in vitro. The effects of BC on CSC markers were confirmed in primary cells isolated from human CRC tumors. BC supplementation decreased the number and size of tumors and delayed the tumor-onset time in xenograft mice injected with CD133⁺CD44⁺ HCT116 cells. The inhibitory effect of BC on CSC markers and the Wnt/β-catenin signaling pathway in tumors was confirmed in vivo as well. CONCLUSIONS: These results suggest that BC may be a potential therapeutic agent for colon cancer by targeting colon CSCs.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7491-7496
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• 2015

Background: Biomarkers in breast neoplasms provide invaluable information regarding prognosis and help determining the optimal treatment. We investigated the possible correlation between cancer stem cell (CSC) markers (CD133, and ALDH1) in invasive ductal breast carcinomas with some clinicopathological parameters. Aim: To assess the correlation between expression of cancer stem cell (CSC) markers (CD133, and ALDH1) and clinicopathological parameters of invasive ductal breast carcinomas. Materials and Methods: Immunohistochemical analysis of CD133 and ALDH1 was performed on a series of 120 modified radical mastectomy (MRM) specimens diagnosed as invasive ductal breast carcinoma. Results: Expression of both CD133 and ALDH1 was significantly changed and related to tumor size, tumor stage (TNM), and lymph node metastasis. A negative correlation between CD133 and ALDH1 was found. Conclusions: Detecting the expression of CD133 and ALDH1 in invasive ductal breast carcinomas may be of help in more accurately predicting the aggressive properties and determining the optimal treatment.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.7
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• pp.4369-4371
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• 2013

Objective: To evaluate the association of a diagnosis of lung cancer and combined detection of serum carcinoembryonic antigen (CEA), carbohydrateantigen 19-9 (CA19-9), neuron specific enolase (NSE) as well as the cytokeratin 19 fragment (CYFRA21-1). Methods: Serum CEA, CA19-9, NSE and CYFRA21-1 were assessed in 150 patients with lung cancer, 100 patients with benign lung disease and 100 normal control subjects, and differences of expression were compared in each group, and joint effects of these tumor markers in the diagnosis of lung cancer were analyzed. Results: Serum CEA, CA19-9, NSE and CYFRA21-1 in patients with lung cancer were significantly higher than those with benign lung disease and normal controls (p<0.01). It is suggested that these four tumor markers combined together could produce a positive detection rate of 90.2%, significantly higher than that of any single test. Conclusion: Combination detection of CEA, CA19-9, NSE and CYFRA21-1 could significantly improve the sensitivity and specificity in diagnosis of lung cancer, and could be important in early detection.

• Journal of Microbiology and Biotechnology
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• v.25 no.7
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• pp.1036-1046
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• 2015

Extracts from Asian medicinal herbs are known to be successful therapeutic agents against cancer. In this study, the effects of three types of herbal extracts on anti-tumor growth were examined. Among the three types of herbal extracts, H9 showed stronger anti-tumor growth effects than H5 and H11 in vivo. To find the molecular mechanism by which H9 inhibited the proliferation of breast cancer cell lines, the levels of apoptotic markers were examined. Proapoptotic markers, including cleaved PARP and cleaved caspases 3 and 9, were increased, whereas the anti-apoptotic marker Bcl-2 was decreased by H9 treatment. Next, the combined effect of H9 with the chemotherapeutic drugs doxorubicin/cyclophosphamide (AC) on tumor growth was examined using 4T1-tumor-bearing mice. The combined treatment of H9 with AC did not show additive or synergetic anti-tumor growth effects. However, when tumor-bearing mice were co-treated with H9 and the targeted anti-tumor drug trastuzumab, a delay in tumor growth was observed. The combined treatment of H9 and trastuzumab caused an increase of natural killer (NK) cells and a decrease of myeloid-derived suppressor cells (MDSC). Taken together, H9 induces the apoptotic death of tumor cells while increasing anti-tumor immune activity through the enhancement of NK activity and diminishment of MDSC.

• Journal of Korean Traditional Oncology
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• v.24 no.1
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• pp.19-28
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• 2019

Objective : The purpose of this study is to report and observe effects of Integrative Cancer Treatment (ICT) on metastatic breast cancer patient. Method : A left breast cancer patient diagnosed with recurrence on liver and bones April 2018. The patient had received paclitaxel chemotherapy for two months and discontinued it because of tumor progression and side effects. The patient has been treated with ICT since March 2018 and has been taking capecitabine since October 2018. The clinical outcomes were measured by computed tomography, laboratory findings including tumor markers (CEA, CA15-3). The clinical outcomes were measured by computed tomography, laboratory findings including tumor markers (CEA, CA15-3), liver function test (AST, ALT), Eastern Cooperative Oncology Group performance status (ECOG PS), and numeric rating scales (NRS). Results : After the ICT, tumor size was partially decreased accompanying by reducing the levels of tumor markers. Major clinical symptoms induced by paclitaxel chemotherapy were improved. There were no severe adverse events induced by ICT based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. Conclusion : This case suggests that ICT may have synergistic effect for the treatment of metastatic breast cancer patient in conjunction with capecitabine.

• Biomedical Science Letters
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• v.24 no.2
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• pp.76-86
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• 2018

Breast cancer is one of the most common cancers affecting women worldwide. Although the survival rate of breast cancer has increased, breast cancer still results in a high mortality rate. Breast cancer deaths are caused by metastasis that occurs in organ dysfunction. Recently, there have been many studies on circulating tumor cells (CTCs), which are related to breast cancer metastasis in the blood. Recent studies have demonstrated that some CTCs do not express epithelial markers. Therefore, in this study, total RNA was extracted from blood without separating out the CTCs, and the characteristics of the CTCs were analyzed by RT-qPCR. Cyclin D1 and twist-related protein 1 (TWIST1) are well-known markers for predicting the prognosis of patients with breast cancer. However, few studies have demonstrated the use of CCND1 and TWIST1 in blood as diagnostic and prognostic markers of breast cancer. In this study, patients with late-stage breast cancer had overexpressed CCND1 and TWIST1 than patients with different stages of breast cancer (P < 0.001 and P < 0.01, respectively). The relative expression level of CCND1 in survivors was higher than in patients who died (P = 0.06). The relative expression level of TWIST1 in survivors was lower than in patients who died (P = 0.08). Overall CCND1 and TWIST1 were not useful as markers for the diagnosis of breast cancer through blood. However, we showed the possibility of using CCND1 and TWIST1 as prognostic markers, and a large-scale study is needed to confirm the usefulness of these prognostic markers.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6813-6820
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• 2013

The present study was conducted to investigate the prognostic significance of co-expression patterna of HER-2, IL-6, TNF-a and TGF-${\beta}1$ in breast cancer, by correlating the number of markers with positive expression with clinicopathological characteristics indicative of tumor progression and overall survival. One hundred thirty consecutive patients with primary breast cancer were prospectively included and evaluated. Serum concentrations of the above markers were measured by ELISA. Median split was used to subdivide patients with marker positive or negative expression. The presence of ${\geq}3$ positive markers was independently associated with extended lymph node (>3) involvement (aOR, 11.94, p=0.001) and lymphovascular invasion (aOR, 12.04, p=0.018), increasing the prognostic significance of each marker considered separately. Additional prognostic information regarding survival was also provided; as the number of positive markers increased, a gradually reduction of survival time was observed. In addition, patients with 4 positive markers had significantly shorter survival (25 vs 39 months, p=0.006) and a more than 4 fold increased risk of death (aHR, 4.35, p=0.003) compared to patients with 3 positive markers. Our findings suggest that the coexpression pattern of these four markers could be used clinically as a useful marker for tumor extension and outcome of breast cancer.

• Asian-Australasian Journal of Animal Sciences
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• v.22 no.10
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• pp.1359-1365
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• 2009

We performed a genome-wide linkage and quantitative trait locus (QTL) analysis to confirm the existence of QTL affecting Rous Sarcoma Virus (RSV) induced tumor regression, and to estimate their effects on phenotypic variance in an F2 resource population. The F2 population comprised 158 chickens obtained by crossing tumor regressive White Leghorn (WL) and tumor progressive Rhode Island Red (RIR) lines was measured for tumor formation after RSV inoculation. Forty-three tumor progressive and 28 tumor regressive chickens were then used for genome-wide linkage and QTL analysis using a total of 186 microsatellite markers. Microsatellite markers were mapped on 20 autosomal chromosomes. A significant QTL was detected with marker LEI0258 located within the MHC B region on chromosome 16. This QTL had the highest F ratio (9.8) and accounted for 20.1% of the phenotypic variation. Suggestive QTL were also detected on chromosomes 4, 7 and 10. The QTL on chromosome 4 were detected at the 1% chromosome-wide level explaining 17.5% of the phenotypic variation, and the QTLs on chromosome 7 and 10 were detected at the 5% chromosome-wide level and explained 11.1% and 10.5% of the phenotypic variation, respectively. These results indicate that the QTLs in the non-MHC regions play a significant role in RSV-induced tumor regression. The present study constitutes one of the first preliminary reports in domestic chickens for QTLs affecting RSV-induced tumor regression outside the MHC region.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.363-368
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• 2014

Determination of the cause of malignant pleural effusions is important for treatment and management, especially in cases of unknown primaries. There are limited biomarkers available for prediction of the cause of malignant pleural effusion in clinical practice. Hence, we evaluated pleural levels of five tumor biomarkers (CEA, AFP, CA125, CA153 and CA199) in predicting the cause of malignant pleural effusion in a retrospective study. Kruskal-Wallis or Mann-Whitney U tests were carried out to compare levels of tumor markers in pleural effusion among different forms of neoplasia - lung squamous cell carcinoma, adenocarcinoma, or small cell carcinoma, mesothelioma, breast cancer, lymphoma/leukemia and miscellaneous. Receiver operator characteristic analysis was performed to evaluate sensitivity and specificity of biomarkers. The Kruskal-Wallis test showed significant differences in levels of pleural effusion CEA (P<0.01), AFP (P<0.01), CA153 (P<0.01) and CA199 (P<0.01), but not CA125 (P>0.05), among the seven groups. Receiver operator characteristic analysis showed that, compared with other four tumor markers, CA153 was the best biomarker in diagnosing malignant pleural effusions of lung adenocarcinoma (area under curve (AUC): 0.838 (95%confidence interval: 0.787, 0.888); cut-off value: 10.2U/ml; sensitivity: 73.2% (64.4-80.8)%, specificity: 85.2% (77.8-90.8)%), lung squamous cell carcinoma (AUC: 0.716 (0.652, 0.780); cut-off value: 14.2U/ml; sensitivity: 57.6% (50.7-64.3)%, specificity: 91.2% (76.3-98.0)%), and small-cell lung cancer (AUC: 0.812 (0.740, 0.884); cut-off value: 9.7U/ml; sensitivity: 61.5% (55.0-67.8)%, specificity: 94.1% (71.2-99.0)%); CEA was the best biomarker in diagnosing MPEs of mesothelioma (AUC: 0.726 (0.593, 0.858); cut-off value: 1.43ng/ml; sensitivity: 83.7% (78.3-88.2)%, specificity: 61.1% (35.8-82.6)%) and lymphoma/leukemia (AUC: 0.923 (0.872, 0.974); cut-off value: 1.71ng/ml; sensitivity: 82.8% (77.4-87.3)%, specificity: 92.3% (63.9-98.7)%). Thus CA153 and CEA appear to be good biomarkers in diagnosing different causes of malignant pleural effusion. Our findings implied that the two tumor markers may improve the diagnosis and treatment for effusions of unknown primaries.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.17
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• pp.7105-7112
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• 2014

In this study, we investigated oxidative stress and tumor marker levels of polycyclic aromatic hydrocarbons (PAHs) in 136 coke oven workers and in 60 control subjects, and evaluated the correlation between oxidative stress and tumor marker levels. Questionnaires on basic demographic information were also administered. Significant differences in employment time and percentages of alcohol drinkers were observed between the control and exposed groups. PAH exposure was assessed using urinary 1-hydroxy-pyrene (1-OHP) levels and was found to be significantly higher in workers than in the controls. Significant differences (P<0.001) of MDA, GST, LDH, NSE, Cyfra21-1, and of SCC and TNF-a (P<0.0001 and P<0.05, P<0.001, respectively) levels were observed among controls and coke-oven workers, except for bottom coke oven workers. Associations between age and risk of increased TNF-a, smoking and increased GST activities, and drinking with increased MDA concentrations, were marginal (P=0.055, P=0.048, P=0.057, respectively). The association between smoking with MDA (P=0.004), NSE (P=0.005), SCC (P=0.004) andTNF-a (P<0.001), and drinking with TNF-a levels was significant (P=0.012). In addition, a significant positive correlation between oxidative stress and tumor markers was found in the present study. These results suggest that a synergistic increase of oxidative stress and tumor markers induced by PAHs may play a role in toxic responses for PAHs in coke oven workers.