• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7645-7649
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• 2013

Background: Immune functions and their relation to prognosis in breast cancer patients have become areas of great interest in recent years. Correlations between survival outcomes and peripheral blood flow cytometry parameters are therefore of interest. Here we focused on patients with non-metastatic breast cancer (BC). Materials and Methods: A total of 29 patients with pathological confirmed breast carcinoma and flow cytometry data were assessed for overall survival (OS) and progression free survival (PFS). Results: The median age of the patients was 54 years (range, 29-83). Multivariate analysis revealed that OS was significantly associated with absolute cytotoxic T cell count (95%CI, coef 2.26, p=0.035), tumor size (95%CI, coef -14.5, p 0.004), chemotherapy (95%CI, coef 12.9, p 0.0001), MFI of CD4 (95%CI, coef -5.1, P 0.04), MFI of HLA DR (95%CI, coef -5.9, p 0.008) and tumor grade (95%CI, coef -13, P 0.049) with R-Sq(adj)=67%. Similar findings were obtained for PFS. Conclusions: OS and PFS were significantly associated with tumor grade, tumor size, chemotherapy, MFI of CD4, HLA DR and absolute cytotoxic T cell count. The study revealed that MFI of basic CD markers and absolute cytotoxic T cell number may be a prognostic factors in women with non-metastatic BC.

• Archives of Pharmacal Research
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• v.27 no.11
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• pp.1147-1153
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• 2004

Bladder cancer is a common cancer with high risk of recurrence and mortality. Intravesicle chemotherapy after trans-urethral resection is required to prevent tumor recurrence and progression. It has been known that antioxidants enhance the antitumor effect of bacillus Calmette-Guerin (BCG), the most effective intravesical bladder cancer treatment. Capsaicin, the major pungent ingredient in genus Capsicum, has recently been tried as an intravesical drug for overactive bladder and it has also been shown to induce apoptotic cell death in many cancer cells. In this study, we investigated the apoptosis-inducing effect and alterations in the cellular redox state of capsaicin in MBT-2 murine bladder tumor cells. Capsaicin induced apoptotic MBT-2 cell death in a time- and dose-dependent manner. The capsaicin-induced apoptosis was blocked by the pretreatment with Z-VAD-fmk, a broad-range caspase inhibitor, or Ac-DEVD-CHO, a caspase-3 inhibitor. In addition to the caspase-3 activation, capsaicin also induced cytochrome c release and decrease in Bcl-2 protein expression with no changes in the level of Bax. Furthermore, capsaicin at the concentration of inducing apoptosis also markedly reduced the level of reactive oxygen species and lipid peroxidation, implying that capsaicin may enhance the antitumor effect of BCG in bladder cancer treatment. These results further suggest that capsaicin may be a valuable intravesical chemotherapeutic agent for bladder cancers.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.21
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• pp.9479-9485
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• 2014

Background: Cancer initiation and progression are controlled by genetic and epigenetic events. One epigenetic process which is widely known is DNA methylation, a cause of gene silencing. If a gene is silenced the protein which it encodes will not expressed. Objectives: 1. Identify the methylation status of BRCA1 in patients with epithelial ovarian cancer (EOC)and assess BRCA1 protein expression in tumor tissue. 2. Examine whether BRCA1 gene methylation and BRCA1 protein are associated with survival of epithelial ovarian cancer patients. Methods: The study design was a prospective-cohort study, conducted at Sardjito hospital, Yogyakarta, Indonesia. Results: A total of 69 cases were analyzed in this study. The data showed that the methylation status of BRCA1 in EOC was positive in 89.9%, with clear protein expression of BRCA1 in 31.9%. Methylation status and expression of BRCA1 were not prognosticators of EOC patients. Menarche, CA125 level, clinical stage and residual tumor were independent factors for prognosis.

• International Journal of Oral Biology
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• v.39 no.1
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• pp.1-7
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• 2014

Neuromedin B (NMB) acts as a growth factor or a morphogen and plays a role in cancer progression. Indeed, the NMB receptor (NMB-R) is overexpressed in different types of tumors. In our current study, we investigated the involvement of NMB-R in the proliferation of oral cancer cells. Human oral squamous cell carcinoma (SCC) and human oral cancer cells, SCC-25 cells were found to be NMB-R-positive. The NMB-R antagonist PD168368 inhibited the proliferation of SCC-25 cells and reduced their colony formation capacity. We also found that PD168368 induced the cell cycle arrest and apoptosis of SCC-25 cells in a dose-/time-dependent manner. Overall, this antitumor activity of PD168368 in human oral cancer cells suggests that NMB-R is a potential target for the future prevention and treatment of human cancers.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.973-978
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• 2016

Background: Between October 2012 and February 2015, 25 patients with metastatic colorectal cancer (mCRC) (mean age, $57.0{\pm}12.1years$) were granted access to aflibercept via the Aflibercept Named Patient Program at four centers. Materials and Methods: Here we reported the initial experience of aflibercept / FOLFIRI in combination. We evaluated treatment-related adverse events (AEs), progression-free survival (PFS) and overall survival (OS). Results: The majority of the patients experienced gastrointestinal toxicity (grade 1-2), with diarrhea (52%), mucositis (52%), and nausea/vomiting (20%) being largely observed. Neutropenia (16%) and febrile neutropenia (8%) were common grade 3-4 hematological events. Aflibercept-related toxicity was managed as per practice guidelines. No grade 5 event was reported. Median PFS was 6.12 months (95% CI, 4.80-7.20) and OS was 12 months (95% CI, 9.80-14.18). The partial response (PR), stable disease (SD), and progressive disease (PD) rates were 25% (95% CI: 23.4-27.0), 37.5% (95% CI: 31.6-43.3), and 37.5% (95% CI: 22.5-52.5), respectively. Conclusions: Aflibercept/FOLFIRI can be administered safely in a second line setting to Malaysian patients with mCRC, as the AEs experienced were generally reversible and manageable. The safety and efficacy outcomes were consistent with those observed in Western populations.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.12
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• pp.4813-4820
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• 2015

Gastric cancer (GC) is one of the most common cancers, with high incidences in East Asia countries. Most GC patients have been reported with low early diagnosis rate and show extremely poor prognosis. Therefore, it is necessary to develop novel and more sensitive biomarkers to improve early diagnosis and therapy in order to provide longer survival and better quality of life for gastric cancer patients. MicroRNAs (miRNAs) play crucial roles in GC development and progression. miRNAs have emerged as a novel molecular biomarker for cancer diagnosis, prognosis and therapy with surprising stability in tissues, serum or other body fluids. This review summarizes major advances in our current knowledge about potential miRNA biomarkers for GC that have been reported in the past two years.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.6151-6158
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• 2013

Radio frequency ablation (RFA) is an effective means of achieving local control of liver cancer. It is a particularly suitable mode of therapy for small and favorably located tumors. However, local progression rates are substantially higher for large tumors (>3.0 cm). In the current study, we report on a mathematical model based on geometric optimization to treat large liver tumors. A database of mathematical models relevant to the configuration of liver cancer was also established. The specific placement of electrodes and the frequency of ablation were also optimized. In addition, three types of liver cancer lesion were simulated by computer guidance incorporating mathematical models. This approach can be expected to provide a more effective and rationale mechanism for employing RFA in the therapy of hepatic carcinoma.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.sup3
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• pp.279-285
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• 2016

It has been established that different kinds of bacteria agents are involved in various cancers. Although the mechanism of tumorigenesis is not clearly understood, there is evidence for the presence of bacteria within tumors, with at least a progression effect for some bacteria that prepare suitable microenvironments for tumor cell growth. The aim of current study was to evaluate bacterial dysbiosis in sentinel lymph nodes of breast cancer patients. One hundred and twenty three fresh-frozen sentinel lymph nodes and a corresponding number of normal adjacent breast tissue specimens and five normal mastectomy samples were investigated employing RT-PCR. In addition using genus-specific primers were applied. There was a significant differences as presence of Methylobacterium radiotolerance DNA recorded between patients and normal control group (p= 0.0). Based on our research work, further studies into the role of microbes in breast cancer would be of great interest.

• Molecules and Cells
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• v.38 no.2
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• pp.171-179
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• 2015

Prostatic acid phosphatase (PAP) expression increases proportionally with prostate cancer progression, making it useful in prognosticating intermediate to high-risk prostate cancers. A novel ligand that can specifically bind to PAP would be very helpful for guiding prostate cancer therapy. RNA aptamers bind to target molecules with high specificity and have key advantages such as low immunogenicity and easy synthesis. Here, human PAP-specific aptamers were screened from a 2'-fluoropyrimidine (FY)-modified RNA library by SELEX. The candidate aptamer families were identified within six rounds followed by analysis of their sequences and PAP-specific binding. A gel shift assay was used to identify PAP binding aptamers and the 6N aptamer specifically bound to PAP with a Kd value of 118 nM. RT-PCR and fluorescence labeling analyses revealed that the 6N aptamer bound to PAP-positive mammalian cells, such as PC-3 and LNCaP. IMR-90 negative control cells did not bind the 6N aptamer. Systematic minimization analyses revealed that 50 nucleotide sequences and their two hairpin structures in the 6N 2'-FY RNA aptamer were equally important for PAP binding. Renewed interest in PAP combined with the versatility of RNA aptamers, including conjugation of anti-cancer drugs and nano-imaging probes, could open up a new route for early theragnosis of prostate cancer.

• Molecules and Cells
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• v.42 no.1
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• pp.17-27
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• 2019

Ubiquitin-specific protease 44 (USP44) has been implicated in tumor progression and metastasis across various tumors. However, the function of USP44 in prostate cancers and regulatory mechanism of histone-modifying enzymes by USP44 in tumors is not well-understood. Here, we found that enhancer of zeste homolog 2 (EZH2), a histone H3 lysine 27 methyltransferase, is regulated by USP44. We showed that EZH2 is a novel target of USP44 and that the protein stability of EZH2 is upregulated by USP44-mediated deubiquitination. In USP44 knockdown prostate cancer cells, the EZH2 protein level and its gene silencing activity were decreased. Furthermore, USP44 knockdown inhibited the tumorigenic characteristics and cancer stem cell-like behaviors of prostate cancer cells. Inhibition of tumorigenesis caused by USP44 knockdown was recovered by ectopic introduction of EZH2. Additionally, USP44 regulates the protein stability of oncogenic EZH2 mutants. Taken together, our results suggest that USP44 promotes the tumorigenesis of prostate cancer cells partly by stabilizing EZH2 and that USP44 is a viable therapeutic target for treating EZH2-dependent cancers.