• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6663-6667
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• 2013

Purpose: The current research was conducted to investigate the efficacy and safety of pemetrexed given continuously as a basement agent for first-, second- to third line chemotherapy of patients with metastatic lung adenocarcinoma. Patients and Methods: Patients with metastatic lung adenocarcinoma who were diagnosed in Jiangsu Cancer Hospital and Research Insitute, were enrolled. All received pemetrexed 500 $mg/m^2$ (intravenous; on day 1), and another chemotherapieutic agent every 3 weeks until disease progression, or intolerable toxicity. Then the patients were changed to a second line chemotherapy that was still based on pemetrexed 500 $mg/m^2$ and another chemotherapeutic agent differing from the first line example, until disease progression, or intolerable toxicity. When third line chemotherapy was needed, pemetrexed 500 $mg/m^2$ and another new chemotherapeutic agent were combined until disease progression. Evaluation of efficacy was conducted after two cycles of chemotherapy using the Response Evaluation Criteria for Solid Tumors. Toxicity was recorded according to NCI Criteria for Adverse Events version 3.0. Results: From January 2010 to September 2013, 15 patients were enrolled. Their median age was 56 years (range 43 to 77 years). Eight patients were male and 7 female. Five patients (33.3%) achieved PR, while 6 patients (40.0%) remained stable, no CR on first line; and 1 PR (7.7%), 5 stable (38.5%) were recorded when pemetrexed was ordered in second line; 5 patients (41.7%) were stable after pemetrexed was combined in third line; no complete response was observed. Main side effects were grade 1 to 2 neutrophil suppression and thrombocytopenia. Other toxicities included elevated transaminase and oral mucositis, but no treatment related death occurred. Conclusions: Pemetrexed continuously as a basement agent from first-, second- to third line chemotherapy is mildly effective in treating patients with metastatic lung adenocarcinoma with tolerable toxicity.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.11
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• pp.4583-4587
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• 2015

Background: The objectives of this study aimed to detect a CYP2B6 polymorphism in de novo cases of acute myeloid leukemia patients and identify any role in disease progression and outcome. Materials and Methods: DNA was isolated from peripheral blood of 82 newly diagnosed acute myeloid leukemia cases and the CYP2B6 G15631T gene polymorphism was assayed by PCR restriction fragment length polymorphism (PCR-RFLP). Results: The frequency of the GG genotype (wild type) was 48 (58.5%) and that of the mutant type T allele was 34 (41.9%). GT genotype heterozygous variants were found in 28 (34%), and TT genotype homozygous variants in 6 (7.3%) cases. We found no significant association between the CYP2B6 G15631T polymorphism and complete response (CR) (p-value=0.768), FAB classification (p-value=0.51), cytogenetic analysis (p-value=0.673), and overall survival (p-value=0.325). Also, there were no significant links with early toxic death (p-value=0.92) or progression-free survival (PFS) (p-value=0.245). Conclusions: Our results suggest that the CYP2B6 polymorphism has no role in disease progression, therapeutic outcome, patient free survival, early toxic death and overall survival in acute myeloid leukemia patients.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3083-3088
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• 2012

We investigated the prognostic value of pituitary tumor transforming gene 1 (PTTG1) expression according to clinicopathological features among localized or locally advanced prostate cancer cases receiving hormone therapy. A retrospective study involved 64 patients receiving combined androgen blockade treatment was performed. PTTG1 expression was determined by immunohistochemical staining using initial needle biopsy specimens for diagnosis. Associations of PTTG1 with various clinicopathological features and disease-free survival were examined via uni- and multivariate analyses. No association between PTTG1 expression and clinical T stage, Gleason score, pretreatment PSA levels, risk groups was found (p =0.682, 0.184, 0.487, 0.571, respectively). Univariate analysis revealed that increased PTTG1 expression, T3 stage and high risk group were associated with increased risk of disease progression (p =0.000, 0.042, and 0.001), and high PSA level had a tendency to predict disease progression (p =0.056). Cox hazard ratio analysis showed that PTTG1 low expression (p =0.002), PTTG1 high expression (p =0.000) and high risk group (p =0.0147) were significantly related to decreased disease-free survival. In conclusion, PTTG1 expression determined by immunohistochemical staining in needle biopsy specimens for diagnosis is a negative prognostic factor for progression in localized or locally advanced prostate cancer receiving hormone therapy.

• Genomics & Informatics
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• v.7 no.2
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• pp.122-130
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• 2009

A systems biology approach for the identification of perturbed molecular functions is required to understand the complex progressive disease such as breast cancer. In this study, we analyze the microarray data with Gene Ontology terms of molecular functions to select perturbed molecular functional modules in breast cancer tissues based on the definition of Gene ontology Functional Code. The Gene Ontology is three structured vocabularies describing genes and its products in terms of their associated biological processes, cellular components and molecular functions. The Gene Ontology is hierarchically classified as a directed acyclic graph. However, it is difficult to visualize Gene Ontology as a directed tree since a Gene Ontology term may have more than one parent by providing multiple paths from the root. Therefore, we applied the definition of Gene Ontology codes by defining one or more GO code(s) to each GO term to visualize the hierarchical classification of GO terms as a network. The selected molecular functions could be considered as perturbed molecular functional modules that putatively contributes to the progression of disease. We evaluated the method by analyzing microarray dataset of breast cancer tissues; i.e., normal and invasive breast cancer tissues. Based on the integration approach, we selected several interesting perturbed molecular functions that are implicated in the progression of breast cancers. Moreover, these selected molecular functions include several known breast cancer-related genes. It is concluded from this study that the present strategy is capable of selecting perturbed molecular functions that putatively play roles in the progression of diseases and provides an improved interpretability of GO terms based on the definition of Gene Ontology codes.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.4
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• pp.1627-1632
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• 2014

Background: Several studies indicated that the diagnosis season affects the prognosis of some cancers, such as examples in the prostate, colon and breast. This retrospective study aimed to investigate whether the diagnosis and recurrent season impacts the prognosis of epithelial ovarian cancer patients. Methods: From January 2005 to August 2010, 161 epithelial ovarian cancer patients were analyzed and followed up until August 2013. Kaplan-Meier survival curves and the log-rank test were used to make the survival analysis. Multivariate analysis was conducted to identify independent prognostic factors. Results: The prognostic factors of overall survival in epithelial ovarian cancer patients included age, clinical stage, pathological type, histological grade, residual disease after primary surgery, recurrent season and adjuvant chemotherapy cycles. Moreover, clinical stage, histological grade, residual disease after primary surgery, recurrent season and adjuvant chemotherapy cycles also impacted the progression-free survival of epithelial ovarian cancer patients. The diagnosis season did not have a significantly relationship with the survival of operable epithelial ovarian cancer patients. Median overall survival of patients with recurrent month from April to November was 47 months, which was longer (P < 0.001) than that of patients with recurrence month from December to March (19 months). Median progression-free survival of patients with recurrence month from April to November and December to March was 20 and 8 months, respectively (P < 0.001). Conclusion: The recurrence season impacts the survival of epithelial ovarian cancer patients. However, the diagnosed season does not appear to exert a significant influence.

• BMB Reports
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• v.57 no.7
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• pp.336-341
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• 2024

Lung cancer is one of the most significant malignancies, with both high morbidity and mortality. CDK10 is closely related to cancer progression and metastasis. However, its role in lung cancer radioresistance demands further clarification. In this study, we demonstrated that CDK10 was downregulated in lung cancer tissues, and CDK10 expression level was associated with the clinical prognosis in lung cancer patients. We also found that silencing CDK10 promoted lung cancer cell proliferation, migration, and radioresistance. We further verified that silencing CDK10 facilitated the activation of JNK/c-Jun signaling, and c-Jun depletion could reverse the effects of CDK10 knockdown in lung cancer cells. Our findings revealed that CDK10 plays an important role in cell growth and radioresistance by inhibiting JNK/c-Jun signaling pathway in lung cancer. Therefore, CDK10 might be a promising therapeutic target in lung cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.4153-4156
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• 2012

Purpose: To investigate the efficacy and toxicity of a combination of gemcitabine with nedaplatin (GN) or cisplatin (GC) for patients with unresectable or recurrent esophagus squamous cell carcinoma. Methods: Gemcitabine was administered at 1 g/m2 intravenously on days 1 and 8; and nedaplatin or cisplatin were administered at 80 mg/m2 intravenously on day 1. We analyzed the response rate, overall survival time, progression-free survival time, and toxicity in 21 patients treated with GN and 27 patients treated with GC. Results: In patients treated with gemcitabine plus nedaplatin, the ORR was 47.6%, the median progression-free survival time was 4.1 months, and the median survival time was 9.3 months. In patients treated with gemcitabine plus cisplatin, the ORR was 48.2%, the median progression-free survival time was 3.9 months, and the median survival time was 9.1 months, respectively. There were no statistically significant differences in ORR, PFS and OS between the two groups. In both, the most commonly observed toxicities were thrombocytopenia and fatigue. Nausea and vomiting was more frequent in the GC group than in the GN group. Conclusion: Gemcitabine based chemotherapy was effective and tolerable for patients with unresectable or recurrent esophagus squamous cell carcinoma refractory to first line chemotherapy.

• Proceedings of the Korean Society of Toxicology Conference
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• 2006.11a
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• pp.19-24
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• 2006

Mothers against decapentaplegic homolog 4 (SMAD4) is a tumor suppressor gene associated with gastrointestinal carcinogenesis. The aim of the present study was to characterize more precisely its role in the development and progression of human gastric carcinoma. In this study, using tissue microarray analysis of 283 gastric cancers and related lesions, we found loss of SMAD4 protein expression in the cytoplasm (36/114, 32%) and in the nucleus (46/114, 40%) of gastric cancer cells. The loss of nuclear SMAD4 expression in primary tumors correlated significantly with poor survival, and was an independent prognostic marker in multivariate analysis. We also found a substantial decrease in SMAD4 expression at both the RNA and protein level in several human gastric carcinoma cell lines. To identify the genetic and/or epigenetic mechanisms of altered SMAD4 expression in gastric carcinoma, loss of heterozygosity (LOH), promoter hypermethylation, and exon mutations were examined. We found that LOH (20/70, 29%) and promoter hypermethylation (4/73, 5%) were associated with the loss of SMAD4 expression. SMAD4 protein levels wore also affected in certain gastric carcinoma cell lines following incubation with Mc132, a proteasome inhibitor. Taken together, our results indicate that the loss of SMAD4, especially loss of nuclear SMAD4 expression, is involved in gastric cancer progression. The loss of SMAD4 in gastric carcinomas is due to several mechanisms, including LOH, hypermethylation, and proteasome degradation.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.6
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• pp.3871-3875
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• 2013

Purpose: MicroRNAs (miRNAs) are small endogenous, non-coding, single-stranded RNAs (approximately 22 nt). Accumulating evidence has shown that aberrant miRNA expression is pronounced and correlated with gastric cancer genesis and progression. Materials and Methods: Expression levels of miR-181a-5p in GC tissues and cell lines were assessed by qRT-PCR and tested for correlation with clinical features. In addition, effects of miR-181a-5p on GC cell growth were investigated. Results: Our findings indicate that miR-181a-5p is upregulated in GC, in correlation with lymph node invasion, nerve invasion and vascular invasion (P<0.05). Enforced expression of miR-181a -5p promoted cell proliferation ability. Conclusions: This study suggested that increased miR-181a-5p is related to GC progression. MiR-181a-5p may represent a potential therapeutic target for GC.

• Biomolecules & Therapeutics
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• v.27 no.2
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• pp.210-215
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• 2019

Colorectal cancer is one of the leading causes of cancer related death due to a poor prognosis. In this study, we investigated the effect of Gomisin G on colon cancer growth and examined the underlying mechanism of action. We found that Gomisin G significantly suppressed the viability and colony formation of LoVo cells. Gomisin G reduced the phosphorylation level of AKT implying that Gomisin G suppressed the PI3K-AKT signaling pathway. Gomisin G also induced apoptosis shown by Annexin V staining and an increased level of cleaved poly-ADP ribose polymerase (PARP) and Caspase-3 proteins. Furthermore, Gomisin G remarkably triggered the accumulation of cells at the sub-G1 phase which represents apoptotic cells. In addition, the level of cyclin D1 and phosphorylated retinoblastoma tumor suppressor protein (Rb) was also reduced by the treatment with Gomisin G thus curtailing cell cycle progression. These findings show the suppressive effect of Gomisin G by inhibiting proliferation and inducing apoptosis in LoVo cells. Taken together, these results suggest Gomisin G could be developed as a potential therapeutic compound against colon cancer.