• Radiation Oncology Journal
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• v.32 no.2
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• pp.49-56
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• 2014

Purpose: Survival outcome of locally advanced pancreatic cancer has been poor and little is known about prognostic factors of the disease, especially in locally advanced cases treated with concurrent chemoradiation. This study was to analyze overall survival and prognostic factors of patients treated with concurrent chemoradiotherapy (CCRT) in locally advanced pancreatic cancer. Materials and Methods: Medical records of 34 patients diagnosed with unresectable pancreatic cancer and treated with definitive CCRT, from December 2003 to December 2012, were reviewed. Median prescribed radiation dose was 50.4 Gy (range, 41.4 to 55.8 Gy), once daily, five times per week, 1.8 to 3 Gy per fraction. Results: With a mean follow-up of 10 months (range, 0 to 49 months), median overall survival was 9 months. The 1- and 2-year survival rates were 40% and 10%, respectively. Median and mean time to progression were 5 and 7 months, respectively. Prognostic parameters related to overall survival were post-CCRT CA19-9 (p = 0.02), the Eastern Cooperative Oncology Group (ECOG) status (p < 0.01), and radiation dose (p = 0.04) according to univariate analysis. In multivariate analysis, post-CCRT CA19-9 value below 180 U/mL and ECOG status 0 or 1 were statistically significant independent prognostic factors associated with improved overall survival (p < 0.01 and p = 0.02, respectively). Conclusion: Overall treatment results in locally advanced pancreatic cancer are relatively poor and few improvements have been accomplished in the past decades. Post-treatment CA19-9 below 180 U/mL and ECOG performance status 0 and 1 were significantly associated with an improved overall survival.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.19
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• pp.8177-8182
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• 2014

Background: Blocking angiogenesis by targeting vascular endothelial growth factor (VEGF) signaling pathway to inhibit tumor growth has proven to be successful in treating a variety of different metastatic tumor types, including kidney, colon, ovarian, and lung cancers, but its role in castration-resistant prostate cancer (CRPC) is still unknown. We here aimed to determine the efficacy and toxicities of anti-VEGF agents in patients with CRPC. Materials and Methods: The databases of PubMed, Web of Science and abstracts presented at the American Society of Clinical Oncology up to March 31, 2014 were searched for relevant articles. Pooled estimates of the objective response rate (ORR) and prostate-specific antigen (PSA) response rate (decline ${\geq}50%$) were calculated using the Comprehensive Meta-Analysis (version 2.2.064) software. Median weighted progression-free survival (PFS) and overall survival (OS) time for anti-VEGF monotherapy and anti-VEGF-based doublets were compared by two-sided Student's t test. Results: A total of 3,841 patients from 19 prospective studies (4 randomized controlled trials and 15 prospective nonrandomized cohort studies) were included for analysis. The pooled ORR was 12.4% with a higher response rate of 26.4% (95%CI, 13.6-44.9%) for anti-VEGF-based combinations vs. 6.7% (95%CI, 3.5-12.7%) for anti-VEGF alone (p=0.004). Similarly, the pooled PSA response rate was 32.4% with a higher PSA response rate of 52.8% (95%CI: 40.2-65.1%) for anti-VEGF-based combinations vs. 7.3% (95%CI, 3.6-14.2%) for anti-VEGF alone (p<0.001). Median PFS and OS were 6.9 and 22.1 months with weighted median PFS of 5.6 vs. 6.9 months (p<0.001) and weighted median OS of 13.1 vs. 22.1 months (p<0.001) for anti-VEGF monotherapy vs. anti-VEGF-based doublets. Conclusions: With available evidence, this pooled analysis indicates that anti-VEGF monotherapy has a modest effect in patients with CRPC, and clinical benefits gained from anti-VEGF-based doublets appear greater than anti-VEGF monotherapy.

• Journal of Life Science
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• v.15 no.5 s.72
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• pp.726-733
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• 2005

Histone deacetylase (HDAC) inhibitors target key steps of tumor development. They inhibit proliferation, induce differentiation and/or apoptotic cell death, and exhibit potent antimetastatic and antiangiogenic properties in cancer cells in vitro and in vivo. Although they are emerging as a promising new treatment strategy in malignancy, how they exert their effect on human non-small cell lung cancer cells is as yet unclear. The present study was undertaken to investiate the underlying mechanism of a HDAC inhibitor trichostatin A (TSA)-induced growth arrest and its effect on the cell cycle control gene products in a human lung carcinoma cell line A549. TSA treaoent induced the growth inhibition and morphological changes in a concentration-dependent manner. Treatment of A549 cells with TSA resulted in a concentration-dependent increased G1 (under 100 ng/ml) and/or G2/M (200 ng/ml) cell population of the cell cycle as determined by flow cytometry Moreover, 200 ng/ml TSA treatment significantly induced the population of sub-G1 cells (23.0 fold of control). This anti-proliferative effect of TSA was accompanied by a marked inhibition of cyclins, positive regulators of cell cycle progression, and cyclin-dependent kinases (Cdks) expression and concomitant induction of tumor suppressor p53 and Cdk inhibitors such as p21 and p27 Although further studies are needed, these findings provide important insights into the possible molecular mechanisms of the anti-cancer activity of TSA in human lung carcinoma cells.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.32 no.3
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• pp.209-215
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• 2006

Preoperative neoadjuvant chemotherapy using cisplatin and 5-FU is generally given in oral and maxillofacial cancer. At tissue level both inflammation and fibrosis occur after chemotherapy. The cellular changes mimic those of a granulating wound, with activated macrophages and fibroblasts replacing the malignant cells as they are erradicated. Stromal cells, together with extracellular matrix components, provide the microenvironment that is pivotal for tumor cell growth, invasion, and metastatic progression. Vascular endothelial growth factor(VEGF), an important regulator of angiogenesis in cancer, induces mitogenesis of vascular endothelial cells, and vascular permeabilization and microvessel formation in a tumor are associated with tumor nutrition and oxygenation. Also, they are associated with chemotherapeutic drug delivery. Oxygen delivery to tumor appears to rely on a network of microvessels, On the other hand, the tumor microvessel is clearly an important factor in chemotherapeutic drug delivery to cancer cells, and the efficacy of drug delivery can be high in richly vascularized tumors. So, this study was conducted to evaluate the effect of neoadjuvant chemotherapy on microvessel density from 11 patients with tongue cancers. Our results showed that neoadjuvant chemotherapy was seemed to decrease VEGF expression in tumor cells, however, it did not significantly alter VEGF expression in tumor-associated macrophages. Also, Neoadjuvant chemotherapy had little effect on the microvessel density using CD34, and tumor-associated macrophage level using CD68. Thus, tumorassociated macrophages seem to be the key factor associated with the maintenance of microvessel density after neoadjuvant chemotherapy in tongue cancer.

• Biomolecules & Therapeutics
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• v.28 no.6
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• pp.561-568
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• 2020

We examined the anticancer effects of a novel sirtuin inhibitor, MHY2256, on HCT116 human colorectal cancer cells to investigate its underlying molecular mechanisms. MHY2256 significantly suppressed the activity of sirtuin 1 and expression levels of sirtuin 1/2 and stimulated acetylation of forkhead box O1, which is a target protein of sirtuin 1. Treatment with MHY2256 inhibited the growth of the HCT116 (TP53 wild-type), HT-29 (TP53 mutant), and DLD-1 (TP53 mutant) human colorectal cancer cell lines. In addition, MHY2256 induced G0/G1 phase arrest of the cell cycle progression, which was accompanied by the reduction of cyclin D1 and cyclin E and the decrease of cyclin-dependent kinase 2, cyclin-dependent kinase 4, cyclin-dependent kinase 6, phosphorylated retinoblastoma protein, and E2F transcription factor 1. Apoptosis induction was shown by DNA fragmentation and increase in late apoptosis, which were detected using flow cytometric analysis. MHY2256 downregulated expression levels of procaspase-8, -9, and -3 and led to subsequent poly(ADP-ribose) polymerase cleavage. MHY2256-induced apoptosis was involved in the activation of caspase-8, -9, and -3 and was prevented by pretreatment with Z-VAD-FMK, a pan-caspase inhibitor. Furthermore, the autophagic effects of MHY2256 were observed as cytoplasmic vacuolation, green fluorescent protein-light-chain 3 punctate dots, accumulation of acidic vesicular organelles, and upregulated expression level of light-chain 3-II. Taken together, these results suggest that MHY2256 could be a potential novel sirtuin inhibitor for the chemoprevention or treatment of colorectal cancer or both.

• Journal of Microbiology and Biotechnology
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• v.30 no.2
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• pp.279-286
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• 2020

A novel compound named 'kanakugiol' was recently isolated from Lindera erythrocarpa and showed free radical-scavenging and antifungal activities. However, the details of the anti-cancer effect of kanakugiol on breast cancer cells remain unclear. We investigated the effect of kanakugiol on the growth of MCF-7 human breast cancer cells. Kanakugiol affected cell cycle progression, and decreased cell viability in MCF-7 cells in a dose-dependent manner. It also enhanced PARP cleavage (50 kDa), whereas DNA laddering was not induced. FACS analysis with annexin V-FITC/PI staining showed necrosis induction in kanakugiol-treated cells. Caspase-9 cleavage was also induced. Expression of death receptors was not altered. However, Bcl-2 expression was suppressed, and mitochondrial membrane potential collapsed, indicating limited apoptosis induction by kanakugiol. Immunofluorescence analysis using α-tubulin staining revealed mitotic exit without cytokinesis (4N cells with two nuclei) due to kanakugiol treatment, suggesting that mitotic catastrophe may have been induced via microtubule destabilization. Furthermore, cell cycle analysis results also indicated mitotic catastrophe after cell cycle arrest in MCF-7 cells due to kanakugiol treatment. These findings suggest that kanakugiol inhibits cell proliferation and promotes cell death by inducing mitotic catastrophe after cell cycle arrest. Thus, kanakugiol shows potential for use as a drug in the treatment of human breast cancer.

• Korean Journal of Head & Neck Oncology
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• v.17 no.2
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• pp.179-184
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• 2001

Objective: The role of chemotherapy in locally advanced head and neck cancer has been established in nasopharynx and larynx as definitive therapy and organ preserving therapy, respectively. Oral cavity cancers are relatively uncommon and local recurrence is the main cause of treatment failure. We planned this retrospective study to evaluate the role of neoadjuvant chemotherapy in locally advanced oral cavity cancer patients. Materials and Methods: From 1988 March to 2001 February, locally advanced, previously untreated oral cavity cancer patients who received neoadjuvant chemotherapy were examined. Chemotherapy had been done in the following patients: Histologically proven squamous cell or poorly differentiated carcinoma, stage 3 or 4, and performance state 0-2 patients. Chemotherapy regimen consisted of cisplatin and infusional 5-fluorouracil. Response was evaluated after 2 cycles and in case of no response, definitive local therapy was done; otherwise 3 cycles was done before local treatment. Results: 48 patients were treated and 47 patients were evaluable for responses. Complete response rate was 6.4%(3/47) and partial response 80.0%(38/47), scoring overall response rate of 87.2%. Median time to progression was 27.0 months (95% CI : 0-58months) and overall 5 year survival was 54.8%. 5-year disease-free survival in the patients in remission after local treatment was 51.9%. In multivariate analysis, contributing factor to the survival were response to neoadjuvant chemotherapy and local treatment modalities. Extensive surgery was done in 10 patients and 25 patents (52.1%) was followed up with preserved function. With median follow-up of 57.0 months, 19 recurrences were detected, most of which were local or regional type. Conclusion: Neoadjuvant chemotherapy followed by local treatment in oral cavity cancer showed high response rate and was thought to be effective therapeutic approach especially in view of organ preservation.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10375-10379
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• 2015

Background: XELOX plus bevacizumab (XELOX-Bev) and FOLFIRI plus Bevacizumab (FOLFIRI - Bev) treatments are an effective strategies patients with metastatic colorectal cancer (mCRC).The aim of this study was to compare efficacy of first-line XELOX-Bev treatment vs FOLFIRI-Bev treatment for mCRC. Materials and Methods: A total of 409 patients with mCRC who received chemotherapy were included and divided into 2 groups. Group 1 (n=298) received XELOX-Bev and Group 2 (n=111) FOLFIRI-Bev. Comparisons were made in terms of overall (OS) and progression-free (PFS) survival, response rate (RR), and grade 3-4 toxicity. Results: Median follow-up was 11 months in Group 1 and 15 months for Group 2. Complete remission was observed in 29 (9.7%) and 2 (1.8%) patients, partial remission in 139 (46.6%) and 27 (24.5%), stable disease in 88 (29.5%) and 49 (44.1%) and progressive disease in 42 (14.1%) and 33 (30.0%) patients in Group 1 and 2, respectively. Median OS was 25 months (range 2-57 months, 95%CI; 22.2-27.7) for Group 1 and 20 months (range 1-67 months, 95%CI; 16.8-23.1) for Group 2 (p=0.036). Median PFS was 9.6 months (range 2-36 months, 95%CI; 8.8-10.4) for Group 1 and 9 months (range 1-44 months, 95%CI; 7.4-10.5) for Group 2 (p=0.019). Objective RR was 56.4% in Group 1 and 26.1% in Group 2 (p<0.001). Conclusions: First-line XELOX-Bev is more effective with a better response rate, prolongation of median PFS/OS, and a superior safety profile compared with FOLFIRI-Bev.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.16
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• pp.6949-6954
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• 2014

Background: Recent studies have indicated that microRNA-15a (miR-15a) is dysregulated in breast cancer (BC). We aimed to evaluate the expression of miR-15a in BC tissues and corresponding para-carcinoma tissues. We also focused on effects of miR-15a on cellular behavior of MDA-MB-231 and expression of its target gene synuclein-${\gamma}$ (SNCG). Materials and Methods: The expression levels of miR-15a were analysed in BC formalin fixed paraffin embedded (FFPE) tissues by microarray and quantitative real-time PCR. CCK-8 assays, cell cycle and apoptosis assays were used to explore the potential functions of miR-15a in MDA-MB-231 human BC cells. A luciferase reporter assay confirmed direct targets. Results: Downregulation of miR-15a was detected in most primary BCs. Ectopic expression of miR-15a promoted proliferation and suppressed apoptosis in vivo. Further studies indicated that miR-15a may directly interact with the 3'-untranslated region (3'-UTR) of SNCG mRNA, downregulating its mRNA and protein expression levels. SNCG expression was negatively correlated with miR-15a expression. Conclusions: MiR-15a has a critical role in mediating cell cycle arrest and promoting cell apoptosis of BC, probably by directly targeting SNCG. Thus, it may be involved in development and progression of BC.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.12
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• pp.4781-4786
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• 2014

Background: The purpose of this study was to analyze the predictive value of neutrophil/lymphocyte ratio (NLR) to better clarify which patient groups will benefit the most from particular treatments like bevacizumab. Materials and Methods: A total of 245 treatment-naive metastatic colorectal cancern (mCRC) patients were retrospectively enrolled and divided into 2 groups: 145 group A patients were treated with chemotherapy in combination with bevacizumab, and 100 group B patients were treated as above without bevacizumab. Results: Group A patients had better median overall survival (OS) and progression-free survival (PFS) (24.0 and 9.0 months) than group B patients (20 and 6.0 months) (p=0.033; p=0.015). In patients with low NLR, OS and PFS were significantly longer in group A patients (27 vs 18 months, p=0.001; 11 vs 7 months, p=0.017). Conclusions: We conclude that NLR, a basal cancer related inflammation marker, is associated with the resistance to bevacizumab-based treatments in mCRC patients.