• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.651-658
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• 2013

Uterine leiomyomas (UL) are extremely common neoplasms in women of reproductive age, and are associated with a variety of characteristic choromosomal aberrations (CAs). The p53 gene has been reported to play a crucial role in suppressing the growth of a variety of cancer cells. Therefore, the present study investigated the effects of CAs and the p53 gene on ULs. We performed cytogenetic analysis by G-banding in 10 cases undergoing myomectomy or hysterectomy. Fluorescence in situ hybridization (FISH) with a p53 gene probe was also used on interphase nuclei to screen for deletions. In patients, CAs were found in 23.4% of 500 cells analysed, significantly more frequent than in the control group (p<0.001). In the patients, 76% of the abnormalities were structural aberrations (deletions, translocations and breaks), and only 24% were numerical. Deletions were the most common structural aberration observed in CAs. Among these CAs, specific changes in five loci 1q11, 1q42, 2p23, 5q31 and Xp22 have been found in our patients and these changes were not reported previously in UL. The chromosome breaks were more frequent in cases, from high to low, 1, 2, 6, 9, 3, 5, 10 and 12. Chromosome 22, X, 3, 17 and 18 aneuploidy was observed to be the most frequent among all numerical aberrations. We observed a low frequency of p53 losses (2-11%) in our cases. The increased incidence of autosomal deletions, translocations, chromatid breaks and aneuploidy, could contribute to the progression of the disease along with other chromosomal alterations.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5301-5310
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• 2013

The biological mechanisms of cancer and associations with behavior of tumours need to be studied to understand progression and determine appropriate treatments. Here we investigated expression of VEGF, MMP-9 and E-cadherin in laryngeal SCCs and their relations with clinical behavior. This prospective study was based on 38 surgical specimens from patients with primary laryngeal SCC and data recorded in their cards. Expression of the three factors in tumor tissue was examined using immunohistochemistry and correlations with clinical parameters of primary tumors, regional lymph node metastases, stage of disease, histopathologic differentiation, and vascular/cartilage invasion were investigated. Regarding the cases with positive MMP-9 expression, the difference between well and moderately/poorly differentiated tumors was statistically significant. However, differences between early stage (stage I and II) and late-stage (stage III and IV) tumours, and between positive and negative for pLN metastasis were not. No significant relationship between positive VEGF and tumor differentiation or stage was apparent, but E-cadherin levels significantly differed between well and moderately/poorly differentiated tumours and with the presence of pLN metastasis. E-cadherin staining did not vary between MMP-9 positive and negative cases. In conclusion, MMP-9 may be a negative predictor of differentiation in laryngeal SCC, while E-cadherin is a predictor of differentiation and nodal metastases. Even if the difference between VEGF expression and tumor stage was not statistically significant, it seems that there exists some relationship, which might be clarified with a greater number of cases.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.26 no.2
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• pp.137-145
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• 2000

Carcinogenesis is a multi-stage process that generally consists of at least three steps; initiation, promotion, and progression. If one of these carcinogenic steps were suppressed or delayed, the cancer could be prevented. Cancer chemoprevention is defined to be inhibition or reversal of the carcinogenic process by the specific chemical agents and is a novel approach to cancer management alternative to conventional chemotherapy. Chlorophylln(CHL), a water-soluble derivative of chlorophyll, containing sodium and copper, has been known to be strong antimutagen in several test systems, but its mechanism of antimutagenic action is unknown. In the present experiment, the possibility of CHL as chemopreventive drugs on 7,12-dimethylbenz[a]anthracene(DMBA)-induced hamster buccal pouch carcinogenesis was investigated by mutagenicity test, carcinogenicity test, and frequency or spectrum of H-ras mutations in the both of DMBA-induced and chlorophylln-pretreated-DMBA induced tumor by polymerase chain reaction and non-isotopic restriction fragment length polymorphism. The treatment of CHL reduced the yields and multiplicity of the 0.5% DMBA-induced tumor, 86% to 62.5% and $3.7{\pm}0.6$ to $1.4{\pm}0.3$, respectively. The occurrence of histidine revertant by $20{\mu}mole$ DMBA was inhibited 25.6 to 81.7% by 1 to $5{\mu}M$ CHL in a dose-dependent manner. The mutation rates of H-ras gene in DMBA-induced and CHL-pretreated-DMBA induced tumor were 96%, 94% of which the most mutations were in codon 12/13. These results suggest that CHL inhibits the carcinogenic action of DMBA by the formation of complex between CHL and DMBA or the inhibition of the activation of DMBA in vivo. But CHL did not affect the mutation rates or its spectrum in already formed tumor.

• BMB Reports
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• v.39 no.6
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• pp.730-736
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• 2006

To evaluated the effect of recombinant adenovirus Ad-ODC-AdoMetDCas which can simultaneously express both antisense ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (AdoMetDC) on cell cycle distribution in colorectal cancer cell and investigated underlying regulatory responses, human colorectal cancer cells HT-29 were cultured in RPMI 1640 medium and infected with Ad-ODC-AdoMetDCas. Cell cycle progression was detected by flow cytometry analysis. The expression levels of cell cycle regulated proteins were measured by Western blot analysis. The mRNA level of cyclin D1 was measured by RT-PCR. And a luciferase reporter plasmid of cyclin D1 promoter was constructed to observe the effect of Ad-ODC-AdoMetDCas on cyclin D1 promoter activity. The results showed that recombinant adenovirus Ad-ODC-AdoMetDCas significantly induced $G_1$ arrest, decreased levels of cyclin D1 protein and mRNA and suppressed the promoter activity. Ad-ODC-AdoMetDCas also inhibited nuclear translocation of $\beta$-catenin. In conclusion, downregulation of ODC and AdoMetDC mediated by Ad-ODC-AdoMetDCas transfection induces $G_1$ arrest in HT-29 cells and the arrest was associated with suppression of cyclin D1 expression and inhibition of $\beta$-catenin nuclear translocation. As a new anticancer reagent, the recombinant adenovirus Ad-ODC-AdoMetDCas holds promising hope for the therapy of colorectal cancers.

• Radiation Oncology Journal
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• v.31 no.3
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• pp.147-154
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• 2013

Purpose: To evaluate the role of salvage radiotherapy (RT) for the treatment of regional lymph node recurrence (RLNR) after radical surgery in advanced gastric cancer. Materials and Methods: We retrospectively analyzed medical records of 26 patients who underwent salvage treatment after diagnosis of RLNR between 2006 and 2011. Patients with peritoneal seeding or distant metastasis were excluded. Eighteen patients received RT with or without chemotherapy and the other 8 did chemotherapy only without RT. A three-dimensional conformal RT was performed with median dose of 56 Gy (range, 44 to 60 Gy). Sixteen patients had fluoropyrimidine-based chemotherapy, 5 did taxane-based chemotherapy, and irinotecan was applied in 4. Results: With a median follow-up of 20 months (range, 5 to 57 months), median overall survival (OS) and progression-free survival (PFS) after diagnosis of RLNR were 29 months and 12 months in the entire patients, respectively. Radiotherapy (p = 0.007) and disease-free interval (p = 0.033) were statistically significant factors for OS in multivariate analysis. Median OS was 36 months in patients who received RT and 16 months in those who did not. Furthermore, delivery of RT (p < 0.001), complete remission after salvage treatment (p = 0.040) and performance status (p = 0.023) were associated with a significantly better PFS. Gastrointestinal toxicities from RT were mild in most patients. Conclusion: Salvage RT combined with systemic chemotherapy may be an effective treatment managing RLNR from advanced gastric cancer.

• Journal of Chest Surgery
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• v.48 no.3
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• pp.193-198
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• 2015

Background: Patients on dialysis undergoing surgery belong to a high-risk group. Only a few studies have evaluated the outcome of major thoracic surgical procedures in dialysis patients. We evaluated the outcomes of pulmonary resection for non-small cell lung cancer (NSCLC) in patients on hemodialysis (HD). Methods: Between 2008 and 2013, seven patients on HD underwent pulmonary resection for NSCLC at our institution. We retrospectively reviewed their surgical outcomes and prognoses. Results: The median duration of HD before surgery was 55.0 months. Five patients underwent lobectomy and two patients underwent wedge resection. Postoperative morbidity occurred in three patients, including pulmonary edema combined with pneumonia, cerebral infarction, and delirium. There were no instances of in-hospital mortality, although one patient died of intracranial bleeding 15 days after discharge. During follow-up, three patients (one patient with pathologic stage IIB NSCLC and two patients with pathologic stage IIIA NSCLC) experienced recurrence and died as a result of the progression of the cancer, while the remaining three patients (with pathologic stage I NSCLC) are alive with no evidence of disease. Conclusion: Surgery for NSCLC in HD patients can be performed with acceptable perioperative morbidity. Good medium-term survival in patients with pathologic stage I NSCLC can also be expected. Pulmonary resection seems to be the proper treatment option for dialysis patients with stage I NSCLC.

• Radiation Oncology Journal
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• v.31 no.1
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• pp.18-24
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• 2013

Purpose: The purpose of this study was to assess the clinical outcomes of hypofractionated radiotherapy (HFRT) with three-dimensional conformal technique for medically inoperable patients with early stage non-small-cell lung cancer (NSCLC) and to evaluate prognostic factors. Materials and Methods: We performed a retrospective review of 26 patients who underwent HFRT for early stage NSCLC between September 2005 and August 2011. Only clinical stage T1-3N0 was included. The median RT dose was 70 Gy (range, 60 to 72 Gy) and the median biologically equivalent dose (BED) was 94.5 Gy (range, 78.0 to 100.8 Gy). In 84.6% of patients, 4 Gy per fraction was used. Neoadjuvant chemotherapy with paclitaxel and cisplatin was given to 2 of 26 patients. Results: The median follow-up time for surviving patients was 21 months (range, 13 to 49 months). The overall response rate was 53.9%, and the initial local control rate was 100%. The median survival duration was 27.8 months. Rates of 2-year overall survival, progression-free survival (PFS), local control (LC), and locoregional-free survival (LRFS) were 54.3%, 61.1%, 74.6%, and 61.9%, respectively. Multivariate analysis showed that BED (>90 vs. ${\leq}90$ Gy) was an independent prognostic factor influencing PFS, LC, and LRFS. Severe toxicities over grade 3 were not observed. Conclusion: Radical HFRT can yield satisfactory disease control with acceptable rates of toxicities in medically inoperable patients with early stage NSCLC. HFRT is a viable alternative for clinics and patients ineligible for stereotactic ablative radiotherapy. BED over 90 Gy and 4 Gy per fraction might be appropriate for HFRT.

• Journal of Gastric Cancer
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• v.14 no.1
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• pp.58-62
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• 2014

We report an extremely rare case of primary squamous cell carcinoma of the stomach. A 69-year-old man was admitted to our hospital with a 2-month history of dysphagia and tarry stools. Endoscopic examination revealed a cauliflower-shaped protruding mass along the lesser curvature of the gastric cardia. Biopsy of the lesion revealed squamous cell carcinoma of the stomach. Computed tomography revealed a thickened stomach wall and a mass protruding into the gastric lumen. Total gastrectomy with splenectomy, distal pancreatectomy, and Roux-en-Y reconstruction was performed, together with a lower thoracic esophagectomy via a left thoracotomy. Histopathological examination of the specimen revealed well-differentiated squamous cell carcinoma of the stomach. Postoperative follow-up was uneventful for the first 18 months. However, multiple liver metastases and para-aortic lymph node metastasis developed subsequently. Despite systemic combination chemotherapy, the patient died because of progression of the recurrent tumors. Here, we review the characteristics of 56 cases of gastric squamous cell carcinoma reported in Japan.

• Journal of Microbiology and Biotechnology
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• v.28 no.8
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• pp.1401-1411
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• 2018

The serine-threonine kinase AKT plays a pivotal role in tumor progression and is frequently overactivated in cancer cells; this protein is therefore a critical therapeutic target for cancer intervention. We aimed to identify small molecule inhibitors of the pleckstrin homology (PH) domain of AKT to disrupt binding of phosphatidylinositol-3,4,5-trisphosphate (PIP3), thereby downregulating AKT activity. Liposome pulldown assays coupled with fluorescence spectrometry were used to screen flavonoids for inhibition of the AKT PH-PIP3 interaction. Western blotting was used to determine the effects of the inhibitors on AKT activation in cancer cells, and in silico docking was used for structural analysis and optimization of inhibitor structure. Several flavonoids showing up to 50% inhibition of the AKT PH-PIP3 interaction decreased the level of AKT activation at the cellular level. In addition, the modified flavonoid showed increased inhibitory effects and the approach would be applied to develop anticancer drug candidates. In this study, we provide a rationale for targeting the lipid-binding domain of AKT, rather than the catalytic kinase domain, in anticancer drug development.

• Journal of Applied Biological Chemistry
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• v.57 no.2
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• pp.113-122
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• 2014

A5E is complex of several medicinal herb ethanol extracts. The aim of this study is investigating the anticancer effect for non-small cell lung cancer. The antitumor effects of A5E on NCI-H460 were examined by regulation of cell proliferation, apoptosis, cell cycle arrest, mitochondrial membrane potential (${\Delta}{\Psi}_m$), and apoptosis-related protein. Cell proliferation was measured by MTS assay. Apoptosis induced by A5E was confirmed by Annexin V-fluorescein isothiocyanate (FITC)/Propidium Iodide (PI) staining, and cell cycle arrest was measured by PI staining. NF-${\kappa}B$ translocation was detected by immunofluorescence and MMP (${\Delta}{\Psi}_m$) was measured by JC-1 staining. The expression of extrinsic pathway molecules such as FasL and FADD were elevated, and procaspase-8 was processed by A5E. In addition, intrinsic pathway related molecules were altered. The Bcl-2 and Bcl-xl levels decreased, Bax increased, and cytochrome C was released. In addition, the mitochondrial membrane potential collapsed, and caspase-3 and poly-(ADP-ribose) polymerase were processed by A5E. Moreover, A5E affected the cellular survival pathway involving phosphatidylinositol 3-kinase (PI3K)/Akt and NF-${\kappa}B$. PI3K and Akt were downregulated, also NF-${\kappa}B$ expression was decreased, and nuclear translocalization was inhibited by A5E. These results suggested that A5E delays proliferation, inhibit cell cycle progression and induce apoptosis in human lung cancer cell. We conclude that A5E is a potential anticancer agent for human lung carcinoma.