• IMMUNE NETWORK
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• v.16 no.2
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• pp.99-108
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• 2016

Colorectal cancer is the third leading cancer worldwide. Although incidence and mortality of colorectal cancer are gradually decreasing in the US, patients with metastatic colorectal cancer have poor prognosis with an estimated 5-year survival rate of less than 10%. Over the past decade, advances in combination chemotherapy regimens for colorectal cancer have led to significant improvement in progression-free and overall survival. However, patients with metastatic disease gain little clinical benefit from conventional therapy, which is associated with grade 3~4 toxicity with negative effects on quality of life. In previous clinical studies, cell-based immunotherapy using dendritic cell vaccines and sentinel lymph node T cell therapy showed promising therapeutic results for metastatic colorectal cancer. In our preclinical and previous clinical studies, cytokine-induced killer (CIK) cells treatment for colorectal cancer showed favorable responses without toxicities. Here, we review current treatment options for colorectal cancer and summarize available clinical studies utilizing cell-based immunotherapy. Based on these studies, we recommend the use CIK cell therapy as a promising therapeutic strategy for patients with metastatic colorectal cancer.

• Journal of Life Science
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• v.34 no.4
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• pp.279-285
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• 2024

The zonula occludens (ZO) protein serves as a scaffolding protein, providing structural support at the junctions between cells and the cytoplasmic surface. It acts as a bridge between integral membrane proteins and the cytoskeleton. Besides its structural role, it also participates in regulating cell growth and proliferation. Recent studies have highlighted the involvement of ZO protein in various diseases, including cancer. Specifically, research has indicated that ZO protein influences the cancer microenvironment surrounding cancer cells, thereby facilitating their growth and development. ZO proteins exert diverse functions in the cancer microenvironment, impacting processes such as angiogenesis, inflammatory responses, the epithelial-mesenchymal transition, and interactions with mesenchymal stem cells. The specific mechanisms vary depending on the type of cancer and environmental conditions. Recent research unveiled several signaling pathways involving ZO protein, which could potentially impede cancer progression in the tumor microenvironment. Consequently, these insights open avenues for novel treatment strategies. While the numerous physiological, structural, and morphological roles of ZO protein have been observed at the cellular and in vivo levels, understanding the signaling mechanisms it operates in vivo and how these mechanisms influence the cancer microenvironment remains a challenge. In this review, we delineate the characteristics and regulatory mechanisms of ZO protein in the context of the cancer microenvironment. Additionally, we propose leveraging the properties of ZO protein to devise defense mechanisms within the cancer cell environment and provide an overview of its in vivo role.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2729-2734
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• 2012

Despite clinical advances in anticancer therapy, there is still a need for novel anticancer metabolites, with higher efficacy and lesser side effects. Oroxylum indicum (L.) Vent. is a small tree of the Bignoniaceae family which is well known for its food and medicinal properties. In present study, the chemopreventive properties of O. indicum hot and cold non-polar extracts (petroleum ether and chloroform) were investigated with MDA-MB-231 (cancer cells) and WRL-68 (non-tumor cells) by XTT assay. All the extracts, and particularly the petroleum ether hot extract (PHO), exhibited significantly (P<0.05) higher cytotoxicity in MDA-MB-231 when compared to WRL-68 cells. PHO was then tested for apoptosis induction in estrogen receptor (ER)-negative (MDA-MB-231) and ER-positive (MCF-7) breast cancer cells by cellular DNA fragmentation ELISA, where it proved more efficient in the MDA-MB-231 cells. Further, when PHO was tested for anti-metastatic potential in a cell migration inhibition assay, it exhibited beneficial effects. Thus non-polar extracts of O. indicum (especially PHO) can effectively target ER-negative breast cancer cells to induce apoptosis, without harming normal cells by cancer-specific cytotoxicity. Hence, it could be considered as an extract with candidate precursors to possibly harness or alleviate ER-negative breast cancer progression even in advanced stages of malignancy.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6295-6298
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• 2012

Oxidant/antioxidant balance has been suggested as an important factor for initiation and progression of cancer. The objective of this study was to determine changes in the levels of malondialdehyde (MDA), nitric oxide (NO), total cholesterol, triglycerides, LDL-cholesterol, HDL-cholesterol, total antioxidant capacity (TAC), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) activities in serum samples of breast cancer patients (n=30) and healthy subjects (n=100). MDA and NO levels were found to be increased in breast cancer patients compared to the healthy subject group (p<0.05). Total cholesterol and triglycerides were elevated; and HDL-cholesterol level was found to be decreased in the cancer patients as compared to the healthy subjects (p<0.05). Compared to the healthy group, both serum TAC levels (p<0.001) and activity of SOD and GSH-Px (p=0.05) were found to be decreased in the breast cancer patients as compared to the healthy controls. Considering the data presented in this study, we suggest that free radicals induce lipid eroxidation and peroxidation of unsaturated fatty acid with decreased activity of enzymatic antioxidants in breast cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3681-3685
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• 2012

Background: In breast cancer, estrogen receptors have been demonstrated to interact with transcription factors to regulate target gene expression. However, high-throughput identification of the transcription regulation relationship between transcription factors and their target genes in response to estradiol is still in its infancy. Purpose: Thus, the objective of our study was to interpret the transcription regulation network of MCF7 breast cancer cells exposed to estradiol. Methods: In this work, GSE11352 microarray data were used to identify differentially expressed genes (DEGs). Results: Our results showed that the MYB (v-myb myeloblastosis viral oncogene homolog [avian]), PGR (progesterone receptor), and MYC (v-myc myelocytomatosis viral oncogene homolog [avian]) were hub nodes in our transcriptome network, which may interact with ER and, in turn, regulate target gene expression. MYB can up-regulate MCM3 (minichromosome maintenance 3) and MCM7 expression; PGR can suppress BCL2 (B-cell lymphoma 2) expression; MYC can inhibit TGFB2 (transforming growth factor, beta 2) expression. These genes are associated with breast cancer progression via cell cycling and the $TGF{\beta}$ signaling pathway. Conclusion: Analysis of transcriptional regulation may provide a better understanding of molecular mechanisms and clues to potential therapeutic targets in the treatment of breast cancer.

• BMB Reports
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• v.44 no.12
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• pp.765-771
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• 2011

Cancer treatment has been stratified by companion biomarker tests that serve to provide information on the genetic status of cancer patients and to identify patients who can be expected to respond to a given treatment. This stratification guarantees better efficiency and safety during treatment. Cancer patients, however, marginally benefit from the current companion biomarker-aided treatment regimens, presumably because companion biomarker tests are dependent solely on the mutation status of several genes status quo. In the true sense of the term, "personalized medicine", cancer patients are deemed to be identified individually by their molecular signatures, which are not necessarily confined to genetic mutations. Glycosylation is tremendously dynamic and shows alterations in cancer. Evidence is accumulating that aberrant glycosylation contributes to the development and progression of cancer, holding the promise for use of glycosylation status as a companion biomarker in cancer treatment. There are, however, several challenges derived from the lack of a reliable detection system for aberrant glycosylation, and a limited library of aberrant glycosylation. The challenges should be addressed if glycosylation status is to be used as a companion biomarker in cancer treatment and contribute to the fulfillment of personalized medicine.

• Journal of Digestive Cancer Research
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• v.5 no.1
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• pp.32-36
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• 2017

In unresectable stage IV colorectal cancer, the role of palliative surgery is not defined clearly. The palliative surgery can be categorized into two surgeries; first, palliative primary tumor resection; second, palliative metastatectomy. Several retrospective studies reported initial palliative systemic chemotherapy in unresectable stage IV colorectal cancer did not increase primary tumor related complications such as obstruction, perforation and hemorrhage, so they insisted that primary tumor resection in asymptomatic stage IV colorectal cancer should be preserved. However, in terms of overall survival and cancer-specific or progression-free survival, several retrospective studies, especially using population-based big data, reported favored survivals in palliative primary tumor resection group. And also several studies reported that palliative metastatectomy such as liver resection without resection of lung metastasis showed better overall survivals. But those results from those studies came from retrospective studies and are likely to be affected by selection bias. Prospective randomized studies are needed to define the benefit of palliative primary tumor resection and metastatectomy in unresectable stage IV colorectal cancer. However, based on the updated evidences, the dogma that palliative primary tumor resection should be preserved in asymptomatic unresectable stage IV colorectal cancer should be questioned.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.24
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• pp.10967-10970
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• 2015

Objective: To analyze the efficacy and survival associated factors of gefitinib combined with cisplatin and gemcitabine for advanced non-small cell lung cancer. Materials and Methods: A total of 57 patients with advanced non-small cell lung cancer (NSCLC), who received platinum-based chemotherapy regimens for more than 1 cycle, were treated with gefitinib combined with cisplatin and gemcitabine until disease progression. Efficacy, survival time and adverse reactions were observed. The Kaplan-Meier method was adopted for analysis of survival and Cox regression for associated influencing factors. Results: The patients were followed up until October 31, 2013, and the median follow-up time was 19 months. Of 57 patients, there were 4 (7.0%) with complete remission (CR), 8 (14.0%) with partial remission, 31 (54.4%) with stable disease, and 14 (24.6%) with disease progression. The remission rate was 21.1% and the disease control rate was 75.4%. The median progression-free survival (PFS) time and the median overall survival time were 10 months and 15.2 months. The one-year, two-year and three-year survival rates were 47.4%, 23.3% and 10.0%. Gender and pathological types were the independent risk factors influencing PFS time (P=0.028, P=0.009). Tumor pathological type and early efficacy were independent factors for the prognosis (P=0.018, P=0.000). Adverse reactions were mostly rashes of I~II degree and diarrhea and slightly increasing level of aminopherase. The skin adverse event incidence of III degree or above was 1.8% (1/57) and brain metastasis was foudn in 31.6% (18/57). Conclusions: Gefitinib combined with cisplatin andgemcitabine, is effective for patients with IIIb~IV NSCLC who received multiple cycles of chemotherapy.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.7
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• pp.4255-4259
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• 2013

Background: Soft tissue sarcomas (STS) are a heterogeneous group of tumors, and approximately 40-50% of patients with STS develop metastatic disease. The median overall survival of those patients was 12 months and their 5-year survival rate was 8%. Therefore, study on more effective treatment, especially the targeting therapies, is urgently needed. Objective: To evaluate the efficacy and safety of Endostar$^{(R)}$ combined with chemotherapy in patients with advanced STS. Methods: A retrospective case-series study was conducted in Cancer Institute of PLA, Xinqiao Hospital. A total of 71 patients suffering from advanced STS (IIB - IV) were included, of whom 49 cases treated with chemotherapy alone were defined as the control group and the rest 22 cases treated with the traditional chemotherapy combined with Endostar$^{(R)}$ were defined as the test group. The short-term therapeutic effects including objective response rate (ORR), disease control rate (DCR) and safety were evaluated in the two groups. In the follow-up, progression-free survival (PFS) and overall survival (OS) were also observed. Results: In the test and control groups, the ORR was 18.2% and 12.2%, respectively (P=0.767), and the DCR was 86.4% and 61.2%, respectively (P=0.034). The median time to progression in the test and control groups was 120 days and 70 days with significant difference (P = 0.017), while the median overall survival was 452 days and 286 days without significant difference (P=0.503). The one-year survival rate in the test group and control group was 56.2% and 35.4%, respectively, while the two-year survival rate was 30.2% and 26.5%, respectively. No significant difference in the side effects was found between the two groups. Conclusions: Endostar$^{(R)}$ combined with chemotherapy resulted in a higher DCR and longer PFS in the patients with advanced STS, and the toxicity was tolerable.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.10
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• pp.4719-4722
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• 2016

Background: Glutathione S-transferase M1 (GSTM1) is involved in the detoxification of carcinogenic agents. DNA copy number variants of GSTM1 may be associated with cancer progression and may result in reduced survival time of various cancers. Determination of DNA copy number variants was here used to assess the association between GSTM1 copy number variant and pathological status and survival time of colorectal-cancer patients treated with 5-fluorouracil-based chemotherapy. Methods: One hundred thirteen Thai colorectal-cancer patients were investigated for GSTM1 copy number variant by real-time PCR. Relationships between gene copy number variants and clinico-pathological parameters were determined. Result: Associations were evident between GSTM1 copy number and stage of tumor (P = 0.026) and metastasis at diagnosis (P = 0.049), with odds ratio values of 0.2 and 0.3 respectively. Conclusions: GSTM1 copy number variant was here not related with reduced overall survival for the colorectal-cancer patients receiving 5-FU-based chemotherapy.