• Asian Pacific Journal of Cancer Prevention
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• v.16 no.2
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• pp.679-682
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• 2015

Background: Studies indicate the immediate early response gene 3 (IER3) is involved in many biological processes. Recently, it was discovered that IER3 plays an important role in tumorigenesis and tumor progression. Thus it may be a valuable biomarker in tumor. This study was designed to investigate the expression status of IER3 in primary hepatocarcinoma (PHC) and correlation with clinicopathological parameters. Materials and Methods: Real-time PCR was performed to evaluate the expression levels of IER3 in 62 pathologically diagnosed human PHC specimens. Results: A statistically significant association was disclosed between the expression of IER3 and P53 mutant protein (short for P53), Ki-67, EGFR and the biggest diameter, differentiation grade of tumor. Conclusions: This work is the first to shed light on the potential clinical usefulness of IER3, as an efficient tumor biomarker in PHC.

• BMB Reports
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• v.48 no.8
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• pp.431-437
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• 2015

Notch signaling plays a pivotal role in cell fate determination, cellular development, cellular self-renewal, tumor progression, and has been linked to developmental disorders and carcinogenesis. Notch1 is activated through interactions with the ligands of neighboring cells, and acts as a transcriptional activator in the nucleus. The Notch1 intracellular domain (Notch1-IC) regulates the expression of target genes related to tumor development and progression. The Notch1 protein undergoes modification after translation by posttranslational modification enzymes. Phosphorylation modification is critical for enzymatic activation, complex formation, degradation, and subcellular localization. According to the nuclear cycle, Notch1-IC is degraded by E3 ligase, FBW7 in the nucleus via phosphorylation-dependent degradation. Here, we summarize the Notch signaling pathway, and resolve to understand the role of phosphorylation in the regulation of Notch signaling as well as to understand its relation to cancer. [BMB Reports 2015; 48(8): 431-437]

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6251-6255
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• 2012

Radiation proctitis and radiation cystitis are major complications for patients with cervical carcinoma following radiotherapy. In the present study, we aimed to determine the potential risk factors for the development of radiation proctitis and radiation cystitis after irradiation. A total of 1,518 patients with cervical carcinoma received external beam radiotherapy (EBRT) followed by high-dose-rate intracavitary brachytherapy (HDRICB) in our hospital. The incidences of radiation proctitis and radiation cystitis were recorded and associations with different factors (age, time period, tumor stage) were analyzed with ${\chi}^2$ (chi-squared) and Fisher exact tests. We found that 161 and 94 patients with cervical carcinoma were diagnosed with radiation proctitis and radiation cystitis, respectively, following radiotherapy. The prevalence of Grade I-II radiation proctitis or radiation cystitis was significantly lower than that of Grade III (radiation proctitis: 3.82% vs. 6.76%, P < 0.05; radiation cystitis: 2.31% vs. 3.87%, P < 0.05) and was significantly enhanced in patients with late stage (IIIb) tumor progression compared to those in early stage (Ib, IIa) (P < 0.05). Moreover, the incidence of radiation proctitis and cystitis was not correlated with age or, time period following radiation, for each patient (P > 0.05). These observations indicate that a late stage of tumor progression is a potential risk factor for the incidence of radiation proctitis and cystitis in cervical carcinoma patients receiving radiotherapy.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.691-694
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• 2013

Purpose: By carrying out a meta-analysis of randomized controlled trials that compared sorafenib or combined chemotherapy with placebo or combined chemotherapy, the effectiveness of sorafenib in hepatocellular carcinoma was evaluated in the present study, which also provided clinical practice guidelines of evidence-based-medicine. Methods: We reviewed PubMed citations concerning sorafenib treating hepatocellular carcinoma in randomized controlled trials from Jan 2000 to July 2012. All the literature was extracted by Cochrane systematic reviews and underwent meta-analysis with RewMan 5.0 software. Results: Finally, four papers documenting randomized controlled studies were included. Compared with controls, sorafenib was shown to significantly increase overall survival (OS), time to progression (TTP), and disease control rates (DCR), but not the time to symptom progression (TTSP) in hepatocellular carcinoma patients. The incidence of grade-III/IV adverse reactions, including hand-foot-skin reactions, diarrhea, hypertension and skin rash or desquamation, in sorafenib treatment group was higher than that in controls. However, there was no significant difference in the incidence of hypodynamia between the two groups. Conclusions: Sorafenib exerts significant curative effects in hepatocellular carcinoma.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.6
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• pp.2767-2773
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• 2016

Human glioma, arising from glial cells of the central nervous system, accounts for almost 30%of all brain tumours, neoplasms with a poor prognosis and high mortality rates worldwide. In the present study we assessed tissue architectural modifications associated with macrophage lineage cells, controversial major immune effector cells within the brain, in human glioma tissue samples from eastern India. Ethically cleared post-operative human glioma samples from our collaborative neurosurgery unit with respective CT/MRI and patient history were collected from the Nodal Centre of Neurosciences in Kolkata, over 9 months. Along with conventional histopathology, samples were subjected to silver-gold staining and fluorescence tagged immunophenotyping for the detection of electron dense brain macrophage/microglia cells in glioma tissue, followed by immune-phenotyping of cells. With higher grades, CD11b+/Iba-1+ macrophage/microglia architecture with de-structured boundaries of glioma lesions indicated malfunction and invasive effector state. Present study documented a contribution of microglia to glioma progression in Eastern India.

• Journal of Digestive Cancer Research
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• v.11 no.1
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• pp.9-14
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• 2023

The prevalence of Barrett's esophagus is increasing in South Korea. Several strategies have been tried to prevent its progression to esophageal adenocarcinoma. It is questionable whether the strategies being tried in the West can be applied adequately in South Korea. However, despite the incidence of esophageal adenocarcinoma in the West, which is considerably higher than that in South Korea, the incidence of high-grade dysplasia/esophageal adenocarcinoma in population-based studies is as low as 0.23%/person-year. Therefore, in Korea, where the prevalence is lower than that, it is necessary to select high-risk groups more carefully for chemoprevention. The age of onset of gastroesophageal reflux disease-like symptoms at least once a week is related to the high-risk group rather than the presence or absence of chronic gastroesophageal reflux symptoms. The risk factors for esophageal adenocarcinoma include the patient's sex, age, smoking habit, and obesity. Proton pump inhibitors have a better preventive effect against esophageal adenocarcinoma compared to H2-receptor blockers, but their application to patients in Korea is limited due to the high number of individuals in need of treatment. Therefore, while considering the risk factors for the progression of esophageal adenocarcinoma, the administration of proton pump inhibitors should be considered for gastroesophageal reflux disease.

• Environmental Mutagens and Carcinogens
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• v.19 no.1
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• pp.46-55
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• 1999

To develop a chemopreventive strategy based on the different stages of premalignant lesions, we hypothesized that the inhibitory effect of chemopreventive agents is influenced by different promotion stages during carcinogenesis. DMBA-TPA-induced skin carcinogenesis was used with ICR mice and chlorophyllin (CHL) was applied as a chemopreventive agent. In vitro assay was performed with Salmonella typhi. TA100 to observe any anti-mutagenic activity of CHL against DMBA. Pre-initiation and pre-promotion effects of CHL were observed by CHL treatment before initiation and before promotion. To evaluate the inhibitory effect at different promotion stages, each group was divided into three subgroups after TPA promotion for 6, 18 and 24 weeks, respectively ; the first subgroup was immediately sacrificed after termination of TPA, the second subgroup was treated with CHL, and the third subgroup was sacrificed 8 weeks after termination of TPA without CHL treatment. The degrees of epithelial dysplasia, papilloma formation, and invasive carcinoma were observed histologically, and GST-Pi expression was observed immunohistochemically. ODC mRNA level was analyzed by reverse transcriptase-polymerase chain reaction. Results showed : CHL dose-dependently inhibited the mutation of Salmonella typhi. TA100; the incidence of epithelial dysplasia and papilloma formation was lower in pre-initiation and pre-promotion CHL-treated mice than DMBA-TPA-treated mice; no invasive carcinoma developed in pre-initiation CHL-treated groups, while 67% of DMBA-TPA treated mice had carcinomas; GST-Pi expression decreased when CHL was treated before initiation and before promotion; and when CHL was treated after termination of TPA application at 18 and 24- week-TPA promotion stages, respectively, the incidence of epithelial dysplasia and papilloma was markedly reduced compared to non-treated groups. When comparing the incidence of epithelial dysplasia and papilloma between the immediately-sacrificed subgroup and the non-treated group with a waiting period, we speculated that the 18-week-TPA promotion stage might belong to the promoter-independent progression stage. At the 18-week-TPA promotion stage, the level of ODC mRNA in the CHL-treated group was clearly reduced to the level of normal tissue. Taking these results together, CHL showed both anti-initiation and anti-promotion effects, while the inhibitory effect of CHL was prominent in the 18-week-TPA promotion stage. However, CHL seems to be incapable of completely blocking the progression in the 24-week-TPA promotion stage.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.7
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• pp.4061-4066
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• 2013

The extranodal natural killer/T-cell lymphoma (ENKTL) shows high local or systemic failure rates when radiotherapy (RT) is taken as the primary treatment, suggesting a role for chemotherapy (CT) added to RT for this disease. However, the appropriate mode of combined modality therapy (CMT) has not been fully defined. A total of one hundred and twenty-one patients with ENKTL receiving sandwich CT with RT were reviewed between January 2003 and August 2012. The primary endpoints were the response rate, progression-free survival (PFS), overall survival (OS), and the relapse rate. After the initial CT, there were 84 (69.4%) patients in CR, 22 (18.2%) patients in PR, 9 (7.4%) patients in SD, and 6 (5%) patients in PD, respectively. At the end of RT, the CR, PR, SD, and PD rates for all patients were 90.9% (n=110), 1.7% (n=2), 4.1% (n=5), and 3.3% (n=4), respectively. After a median follow-up of 42.3 months (3.5~112.3 months), the 5-year PFS was 74.7% (95% CI 70.4%~79.0%), and 5-year OS was 77.3% (95% CI 67.9%~86.7%). Disease progression was documented in 25 (20.7%) patients. The rates of systemic failure, local failure, and regional failure were 18.2%, 5.8%, 1.7%, respectively. Twenty death events (16.5%) were observed for the entire group of patients (18 deaths related to PD). Furthermore, CR to the initial CT and low Korean Prognostic Index (KPI) can independently predict long PFS and OS. The sandwich CMT achieved an excellent outcome for localized ENKTL with acceptable toxicity. We recommend it can be applied as the optimal choice for localized ENKTL.

• Journal of Life Science
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• v.25 no.5
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• pp.607-614
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• 2015

Cancers are the largest cause of mortality and morbidity all over the world. Cordycepin, an adenosine analog, is a major functional component of the Cordyceps species, which has been widely used in traditional Oriental medicine. Over the last decade, this compound has been reported to possess many pharmacological properties, such as an ability to enhance immune function, as well as anti-inflammatory, antioxidant and anti-cancer effects. Recently, numerous studies have reported interesting properties of cordycepin as a chemopreventive agent as well. There is an accumulating body of experimental evidences suggesting that cordycepin impedes cancer progression by promoting apoptosis, inducing cell cycle arrest, modulating intracellular signaling pathways, and inhibiting invasion and metastasis of cancer cells. In many cancer cell lines, cordycepin inhibits growth and cell cycle progression by inducing arrest of the G2/M phase, resulting from the inhibition of retinoblastoma protein phosphorylation and induction of cyclin-dependent kinase inhibitors. To induce apoptosis, cordycepin activates the extrinsic and intrinsic pathways, which promotes reactive oxygen species generation and the downstream activation of kinase cascades. Cordycepin also can activate alternative pathways to cell death such autophagy. In addition, cordycepin can inhibit the pro-metastatic processes of cancer cell detachment, migration, and invasion through a variety of mechanisms, including the nuclear factor-kappa B and activated protein-1 signaling pathways. In this review, we summarized the variety of action mechanisms by which cordycepin may mediate chemopreventive effects on cancer and discussed the potential of this natural product as a promising therapeutic inhibitor of cancer development.

• Journal of Digestive Cancer Research
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• v.2 no.1
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• pp.28-31
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• 2014

Pancreatic cancer is a highly aggressive cancer with poor prognosis. Although, gemcitabine is the current standard regimen as first-line chemotherapy for advanced pancreatic cancer, effective regimens of second-line chemotherapy after gemcitabine failure have not been established yet. We report a case of gemcitabine refractory pancreatic cancer treated with second-line chemotherapy with FOLFIRINOX regimen. A 57-year-old-woman visited our hospital for pancreatic body mass detected by computed tomography (CT). The patient underwent distal pancreatectomy and splenectomy and the pathologic results after surgery demonstrated adenocarcinoma. Follow-up was performed after surgery and CT and positron emission tomography (PET) 4 months after surgery revealed multiple hepatic metastases. The patient underwent first-line chemotherapy with gemcitabine and erlotinib for recurred pancreatic cancer. However, CT after 7 cycles of the chemotherapy showed the progression of multiple hepatic metastases and switch to second-line chemotherapy with FOLFIRINOX was initiated. CT after 16 cycles of the FOLFIRINOX showed the complete remission of multiple hepatic metastases. The patient was admitted for infective endocarditis with septic pneumonia 17 months after the initiation of FOLFIRINOX. However, the patients died from the progression of septic embolism and acute respiratory distress syndrome.