• Asian Pacific Journal of Cancer Prevention
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• v.15 no.12
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• pp.4745-4751
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• 2014

Oxidative stress is caused by an imbalance in the redox status of the body. In such a state, increase of free radicals in the body can lead to tissue damage. One of the most important species of free radicals is reactive oxygen species (ROS) produced by various metabolic pathways, including aerobic metabolism in the mitochondrial respiratory chain. It plays a critical role in the initiation and progression of various types of cancers. ROS affects different signaling pathways, including growth factors and mitogenic pathways, and controls many cellular processes, including cell proliferation, and thus stimulates the uncontrolled growth of cells which encourages the development of tumors and begins the process of carcinogenesis. Increased oxidative stress caused by reactive species can reduce the body's antioxidant defense against angiogenesis and metastasis in cancer cells. These processes are main factors in the development of cancer. Bimolecular reactions cause free radicals in which create such compounds as malondialdehyde (MDA) and hydroxyguanosine. These substances can be used as indicators of cancer. In this review, free radicals as oxidizing agents, antioxidants as the immune system, and the role of oxidative stress in cancer, particularly breast cancer, have been investigated in the hope that better identification of the factors involved in the occurrence and spread of cancer will improve the identification of treatment goals.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.6
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• pp.2419-2423
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• 2015

Background: There are few choices for treatment of advanced cancer patients who do not respond to or tolerate conventional anti-cancer treatments. Therefore this study aimed to deploy the benefits and clinical efficacy of continuous dendritic cell-cytokine induced killer cell infusions in such patients. Materials and Methods: A total of 381 infusions (from 67 advanced cases recruited) were included in this study. All patients underwent peripheral blood mononuclear cell apheresis for the following cellular therapy and dendritic cells-cytokine induced killer cells were expanded in vitro. Peripheral blood T lymphocyte subsets were quantified through flow cytometry to address the cellular immunity status. Clinical efficacy and physical activities were evaluated by RECIST criteria and Eastern Cooperative Oncology Group scores respectively. Logistic regression model was used to estimate the association between cellular infusions and clinical benefits. Results: An average of $5.7{\pm}2.94{\times}10^9$ induced cells were infused each time and patients were exposed to 6 infusions. Cellular immunity was improved in that cytotoxic $CD8^+CD28^+$ T lymphocytes were increased by 74% and suppressive $CD8^+CD28^-$ T lymphocytes were elevated by 16% (p<0.05). Continuous infusion of dendritic cells-cytokine induced killer cells was associated with improvement of both patient status and cellular immunity. A median of six infusions were capable of reducing risk of progression by 70% (95%CI 0.10-0.91). Every elevation of one ECOG score corresponded to a 3.90-fold higher progression risk (p<0.05) and 1% increase of $CD8^+CD28^-$ T cell proportion reflecting a 5% higher risk of progression (p<0.05). Conclusions: In advanced cancer patients, continuous dendritic cell-cytokine induced killer cell infusions are capable of recovering cellular immunity, improving patient status and quality of life in those who are unresponsive to conventional cancer treatment.

• Biomedical Science Letters
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• v.8 no.3
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• pp.137-142
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• 2002

The expression of CD44v is known as a marker of cancer progression and its metastasis in colorectal cancer. It has been known that CD44 variant containing sequences encoded by exon 11 (v6) confer metastatic potential to human colorectal cancer cells. The role of CD44 standard (CD44s) and CD44v6 in colorectal cancer was investigated in this study by immunohistochemical staining of the primary tumors obtained from the colorectal cancer patients. Immunohistochemical staining was performed in 40 patients with colorectal cancer who underwent curative surgery at Keimyung University hospital. The expression CD44s and CD44v6 was observed in 24/40 (60%) and 13/40 (32.5%) respectively. The expression of CD44v6 had correlation with TNM stage (P＜0.05), however CD44s had not any correlation with clinicopathological parameters. These results suggest that CD44v6 expression may give an information for tumor progression than decreased expression of CD44s in colorectal cancer cells.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.10
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• pp.4233-4238
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• 2014

Background: The aim of this study was to investigate the relationship of body mass index with overall and progression-free survival as well as other prognostic factors of breast cancer in patients with non-metastatic breast cancer. Materials and Methods: We retrospectively reviewed 456 patients diagnosed with breast cancer in the Radiation Oncology department of Kayseri Teaching Hospital between 2005 and 2013. We investigated relationship of body mass index with prognosis and other prognostic factors. Results: The study included 456 patients (447 women and 9 men). Mean age at presentation was 55.6 years. Of the cases, 96.9% underwent modified radical mastectomy and 95.0% received chemotherapy, while 82.4% received radiotherapy and 60.0% were given hormone therapy. Body mass index was >25 mg/kg2 in 343 cases. Five- and 10-years overall survival rates were 77% and 58% whereas progression-free survival rates were 65% and 49%, respectively. In univariate analyses, factors including stage (p=0.046), tumor diameter (p=0.001), lymph node metastasis (p=0.006) and body mass index (p=0.030) were found to be significantly associated with overall survival, while perinodal involvement was found to be significantly associated with progression-free survival (p=0.018). In multivariate analysis, stage (p=0.032; OR: 3.8; 95% CI: 1.1-13), tumor diameter (p<0.000; OR: 0.0; 95% CI: 0.0-0.3), lymph node metastasis (p=0.005; OR: 0.0; 95% CI: 0.0-0.5) and BMI (p=0.027; OR: 0.02; 95% CI: 0.0-0.8) remained as significantly associated with OS. Conclusions: In our study, it was seen that overall survival time was shorter in underweight and obese patients when compared to normal weight patients.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.20
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• pp.8987-8992
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• 2014

Background: The efficacy of concurrent chemoradiotherapy in the treatment of locally advanced cervical cancer is well established. We aimed to investigate the long-term efficacy of definitive concurrent chemoradiotherapy for cervical cancer in the University of Malaya Medical Centre. Materials and Methods: A cohort of 60 patients with FIGO stage IB2-IVA cervical cancer who were treated with definitive concurrent chemoradiotherapy with cisplatin followed by intracavitary brachytherapy or external beam radiotherapy (EBRT) boost between November 2001 and May 2008 were analysed. Patients were initially treated with weekly intravenous cisplatin ($40mg/m^2$) concurrent with daily EBRT to pelvis of 45-50Gy followed by low dose rate brachytherapy or EBRT boost to tumour. Local control rate, progression free survival, overall survival and treatment related toxicities graded by the RTOG criteria were evaluated. Results: The mean age was 56. At the median follow-up of 72 months, the estimated 5-year progression-free survival (PFS) (median PFS 39 months) and the 5-year overall survival (OS) (median OS 51 months) were 48% and 50% respectively. The 5-year local control rate was 67.3%. Grade 3-4 late gastrointestinal and genitourinary toxicity occurred in 9.3% of patients. Conclusions: The 5-year PFS and the 5-year OS in this cohort were lower than in other institutions. More advanced stage at presentation, longer overall treatment time (OTT) of more than fifty-six days and lower total dose to point A were the potential factors contributing to a lower survival.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4815-4822
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• 2012

Invasion and metastasis are the major causes of cancer-related death. Pharmacological or therapeutic interventions such as chemoprevention of the progression stages of neoplastic development could result in substantial reduction in the incidence of cancer mortality. (-)-Epigallocatechin-3-gallate (EGCG), a promising chemopreventive agent, has attracted extensive interest for cancer therapy utilizing its antioxidant, anti-proliferative and inhibitory effects on angiogenesis and tumor cell invasion. In this study, we assessed the influence of EGCG on the proliferative potential of HeLa cells by cell viability assay and authenticated the results by nuclear morphological examination, DNA laddering assay and cell cycle analysis. Further we analyzed the anti-invasive properties of EGCG by wound migration assay and gene expression of MMP-9 and TIMP-1 in HeLa cells. Our results indicated that EGCG induced growth inhibition of HeLa cells in a dose- and time-dependent manner. It was observed that cell death mediated by EGCG was through apoptosis. Interestingly, EGCG effectively inhibited invasion and migration of HeLa cells and modulated the expression of related genes (MMP-9 and TIMP-1). These results indicate that EGCG may effectively suppress promotion and progression stages of cervical cancer development.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.3
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• pp.1145-1148
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• 2014

Background: Single pegylated liposomal doxorubicin (PLD) is commonly used as a salvage treatment in platinum-resistant ovarian cancer, fallopian tube cancer and primary peritoneal adenocarcinoma (PPA) with a satisfactory outcome. However, the data for second generation PLD administered in this setting are still limited. We conducted a retrospective study to evaluate the outcome of patients who received single-agent second generation PLD (LIPO-DOX) after the development of clinical platinum resistance. The study period was between March 2008 and March 2013. LIPO-DOX was administered intravenously 40 $mg/m^2$ every 28 days until disease progression, but for not more than six cycles. The response rate was evaluated using the Gynecologic Cancer Intergroup (GCIG) criteria while the toxicity was evaluated according to WHO criteria. Twenty-nine patients met the inclusion criteria in the study period with an overall response rate of 13.8%. The median progression free survival and overall survival were three and eleven months, respectively. With the total of 96 cycles of chemotherapy, the patients developed grades 3 and 4 hematologic toxicity as follows: anemia, 0%, leukopenia, 9.6%, neutropenia, 32.3% and thrombocytopenia, 0%. In conclusion, the single agent second generation PLD demonstrated modest efficacy in patients with platinum-resistant ovarian cancer, fallopian tube cancer and PPA without serious toxicity.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.11
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• pp.4477-4487
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• 2015

In this review we summarize the results of studies employing high-throughput methods of profiling of HPV-associated cervical intraepithelial neoplasia (CIN) and squamous cell cervical cancers at key intracellular regulatory levels to demonstrate the unique identity of the landscape of molecular changes underlying this oncopathology, and to show how these changes are related to the 'natural history' of cervical cancer progression and the formation of clinically significant properties of tumors. A step-wise character of cervical cancer progression is a morphologically well-described fact and, as evidenced by genome-wide screenings, it is indeed the consistent change of the molecular profiles of HPV-infected epithelial cells through which they progressively acquire the phenotypic hallmarks of cancerous cells. In this sense, CIN/cervical cancer is a unique model for studying the driving forces and mechanisms of carcinogenesis. Recent research has allowed definition of the whole-genome spectrum of both random and regular molecular alterations, as well as changes either common to processes of carcinogenesis or specific for cervical cancer. Despite the existence of questions that are still to be investigated, these findings are of great value for the future development of approaches for the diagnostics and treatment of cervical neoplasms.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.17
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• pp.7245-7249
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• 2014

Glucose regulated protein 78 (GRP78) is usually recognized as a chaperone in the endoplasmic reticulum. However, increasing evidence indicates that GRP78 can be translocated to the cell surface, acting as a signaling receptor for a variety of ligands. Since little is known about the secretion of GRP78 and its role in the progression of colon cancer we here focused on GRP78 from colon cancer cells, and purified GRP78 protein mimicking the secreted GRP78 was able to utilize cell surface GRP78 as its receptor, activating downstream PI3K/Akt and Wnt/${\beta}$-catenin signaling and promote colon cancer cell proliferation. Our study revealed a new mode of action of autocrine GRP78 in cancer progression: secreted GRP78 binds to cell surface GRP78 as its receptor and activates intracellular proliferation signaling.

• Fisheries and Aquatic Sciences
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• v.24 no.1
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• pp.1-9
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• 2021

Human prostate cancer is the second most frequently diagnosed cancer worldwide, and its incidence rate continues to increase. Advanced prostate cancer is more difficult to treat than early forms due to its chemotherapy resistance. There is need for more effective agents that can inhibit the progression of advanced prostate cancer. Demethoxyfumitremorgin C (DMFTC) was isolated from the fermentation extract of the marine fungus Aspergillus fumigatus. Antiproliferative activity of DMFTC against human prostate cancer PC3 cells was examined through cell cycle analysis by flow cytometry, the fluorescent nuclear imaging analysis with propidium iodide (PI), and proteins expression related to cell cycle arrest and apoptosis were investigated via Western blotting. DMFTC inhibited PC3 cells growth through G1 phase cell cycle arrest and apoptosis induction. It activated the tumor suppressor p53 and the Cdk inhibitor p21, which regulate the cell progression into the G1 phase. Additionally, PI-positive late apoptotic non-viable cells were increased and the expression levels of the G1-positive downstream regulators cyclin D, cyclin E, Cdk2, and Cdk4 were decreased by DMFTC treatment. These results suggest that DMFTC induces G1 arrest and apoptosis induction through regulation of p53/p21-dependent cyclin-Cdk complexes, and it may be a useful therapeutic agent for the treatment of human advanced prostate cancer.