• Asian Pacific Journal of Cancer Prevention
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• v.16 no.1
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• pp.195-199
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• 2015

Background: This study was conducted to determine the influence of MACC1 expression on chemotherapy sensitivity in human U251 glioblastoma cells. Materials and Methods: Expression of the MACC1 gene in 49 cases of human brain glioma was determined by quantitative real-time PCR. Silencing effects of RNA interference on MACC1 was detected by Western-blotting. Flow cytometry methods and methyl thiazolyl tetrazolium assay (MTT) were used to determine the apoptosis and growth inhibitory rates of the U251 cells with MACC1 silencing. before and after treatment with cisplatin (DDP). Results: MACC1 mRNA in gliomas was up-regulated remarkably, to 158.8% of that in peri-cancerous tissues (P<0.05). The siRNA-MACC1 could inhibit the expression of MACC1 protein significantly (p<0.05), associated with an increase in apoptosis rate from 2.57% to 5.39% in U251 cells and elevation of the growth inhibitory rate from 1.5% to 17.8% (p<0.05 for both). After treatment with DDP at various concentrations (1, 3, $5{\mu}g/ml$), compared with control U251 cells, the apoptosis rate of MACC1-silenced U251 cells rose from 8.41%, 13.2% and 19.5% to 12.8%, 17.8% and 25.8%; the growth inhibitory rate increased from 16.2%, 19.3% and 24.5% to 23.7%, 28.4% and 36.3%. Conclusions: There is a notable relationship between over-expression of MACC1 and the characteristics of glioma cells. Silencing of MACC1 was found to enhance the apoptosis and growth inhibitory rates of U251 glioma cells, and thereby increase their sensitivity to DDP chemotherapy.

• Current Optics and Photonics
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• v.3 no.3
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• pp.256-262
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• 2019

Extensive tumor resection accompanied by radiotherapy and chemotherapy is the standard of care for malignant gliomas. However, there is a significant obstacle to the complete resection of the tumor due to the difficulty of distinguishing tumor and normal brain tissue with a conventional surgical microscope. Recently, multiple studies have shown the possibility of fluorescence-guided surgery in malignant gliomas. The most used fluorescence dyes for brain tumor surgery are 5-aminolevulinic acid (5-ALA) and indocyanine green (ICG). In this paper, a new fluorescence guided operation system, which can detect both 5-ALA and ICG fluorescent images simultaneously, is presented. This operation system consists of light emitting diodes (LEDs) which emits 410 nm and 740 nm wavelengths. We have performed experiments on rats in order to verify the operation of the newly developed operation system. Oral administration and imaging were performed to observe the fluorescence of 5-ALA and ICG fluorescence in rats. When LEDs at wavelengths of 410 nm and 740 nm were irradiated on rats, 628 nm wavelength with a violet fluorescence color and 825 nm wavelength with a red fluorescence color were expressed in 5-ALA and ICG fluorescent material, respectively, thus we were able to distinguish the tumor tissues easily. Previously, due to the poor resolution of the conventional surgical microscope and the fact that the color of the vein is similar to that of the tumor, the tumor resection margin was not easy to observe, thus increasing the likelihood for cancer recurrence. However, when the tumor is observed through the fluorescence guided operation system, it is possible to easily distinguish the color with the naked eye and it can be completely removed. Therefore, it is expected that surgical removal of cancerous tumors will be possible and surgical applications and surgical microscopes for cancer tumor removal surgery will be promising in the future.

• Genomics & Informatics
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• v.21 no.1
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• pp.8.1-8.19
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• 2023

Cancer of the stomach is the second most frequent cancer-related death worldwide. The survival rate of patients with gastric cancer (GC) remains fragile. There is a requirement to discover biomarkers for prognosis approaches. Helicobacter pylori in the stomach is closely associated with the progression of GC. We identified the genes associated with poor/favorable prognosis in H. pylori-induced GC. Multivariate statistical analysis was applied on the Gene Expression Omnibus (GEO) dataset GSE54397 to identify differentially expressed miRNAs (DEMs) in gastric tissues with H. pylori-induced cancer compared with the H. pylori-positive with non-cancerous tissue. A protein interaction map (PIM) was built and subjected to DEMs targets. The enriched pathways and biological processes within the PIM were identified based on substantial clusters. Thereafter, the most critical genes in the PIM were illustrated, and their prognostic impact in GC was investigated. Considering p-value less than 0.01 and |Log2 fold change| as >1, five microRNAs demonstrated significant changes among the two groups. Gene functional analysis revealed that the ubiquitination system, neddylation pathway, and ciliary process are primarily involved in H. pylori-induced GC. Survival analysis illustrated that the overexpression of DOCK4, GNAS, CTGF, TGF-b1, ESR1, SELE, TIMP3, SMARCE1, and TXNIP was associated with poor prognosis, while increased MRPS5 expression was related to a favorable prognosis in GC patients. DOCK4, GNAS, CTGF, TGF-b1, ESR1, SELE, TIMP3, SMARCE1, TXNIP, and MRPS5 may be considered prognostic biomarkers for H. pylori-induced GC. However, experimental validation is necessary in the future.

• Tuberculosis and Respiratory Diseases
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• v.42 no.4
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• pp.492-501
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• 1995

Background: Transforming growth factor- alpha(TGF-$\alpha$) may play important roles in carcinogenesis, tumor growth, and angiogenesis. Transforming growth factor-beta(TGF-$\beta$) are known to be involved in cell-cycle control and regeneration. TGF-$\alpha$ positively acts on growth control of many epithelial cells in contrast to the negative role of TGF-$\beta$. Method: To evaluate the possible role of TGF-$\alpha$ and TGF-$\beta$ in human primary lung cancers, the expression of TGF-$\alpha$ and TGF-$\beta$ were immmunohistochemically investigated in tissue sections from forty seven cases with lung cancers and ten cases with non-cancerous lung tissues. Recombinant cloned monoclonal antibody of TGF-$\alpha$ and neutralizing antibody of TGF-$\beta$ were employed as primary antibodies after dewaxing the formalin-fixed, paraffinized tissue sections. Results: TGF-$\alpha$ was expressed in the cytoplasms of tumor cells in thirty five cases of forty seven(74.5%) primary lung cancers, whereas the control expressed in two of ten brochial epithelial cells. The expression of TGF-$\alpha$ was disclosed in four cases of eleven(36.4 %) small cell carcinomas and thirty one cases of thirty six(86.1%) non-small cell carcinomas of the lung. Expressions of TGF-$\beta$ was discernible in bronchial epithelium in eight of ten non-cancerous lung tissues. The expression of TGF-$\beta$ was noted in the cytoplasms of tumor cells in eight cases of forty seven(17.0%) primary lung cancers. The expression of TGF-$\beta$ disclosed in two cases of eleven(18.2%) small cell carcinomas and six cases of thirty six(16.7%) non- small cell carcinomas of the lung. Conclusion: These findings suggest that up-regulation of TGF-$\alpha$ and down-regulation of TGF-$\beta$ are involved during development and growth of primary lung cancers.

• Tuberculosis and Respiratory Diseases
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• v.46 no.4
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• pp.523-532
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• 1999

Background: With the development of the molecular biological methods, studies of the early diagnosis of lung cancer and the detection in the preneoplastic state by using genetic probes in the high risk groups are widely investigated. In lung cancer, squamous cell carcinoma is considered to progress from the normal bronchial mucosa to the preneoplastic state, and finally to the invasive carcinoma. In this study, we investigated the expression of p53 and c-erbB2 in the normal bronchi and the cancer tissues in patients with squamous cell lung cancer to evaluate the possibility of using these immunohistochemical markers as the diagnostic and prognostic parameters of patients with squamous cell lung cancer. Method: The normal and cancerous bronchial tissues of 25 patients with squamous cell carcinoma of the lung, surgically resected from May 1995 to November 1996, were immunohistochemically stained with the monoclonal antibodies to p53(DAKO-p53) and c-erbB2(phamingen 15821A) respectively. We compared the expression status of these markers between the normal bronchial mucosa and the tumor tissue, and also investigated the relationship between the expression status of these markers in tumor tissues and the pathological stage, and the survival time. Results: The pathological stage was as follows; stage I, II were found in 5 patients respectively, stage IIIA was in 8 patients, stage IIIB was in 4 patients, and stage IV was in 3 patients. The expression rate of p53 in the squamous cell lung cancer was 48%, and it was not expressed in the normal bronchial mucosa. The expression status was increased as the pathological stage advanced(p=0.0091 by test of trend). But there were no relationship between the expression of p53 and the median survival time. C-erbB2 did not yield a significantly meaningful result. Conclusion: p53 was not found in the normal bronchial mucosa, but it was expressed in 48% of the tumor tissue. And the expression rate increased as the pathological stage advanced. So it would be helpful to apply the immunochistochemical stain with p53 in the bronchial biopsy specimen in the early diagnosis trial or staging of squamous cell lung cancer.

• Journal of Life Science
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• v.25 no.8
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• pp.947-952
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• 2015

Prostate apoptosis response-4 (Par-4) was originally identified in androgen-independent prostate cancer cells undergoing apoptosis. Par-4 is ubiquitously expressed in normal cells and tissues, but it is downregulated in several types of cancers. Par-4 is a 38 kDa tumor suppressor protein encoded by the PARW gene. Par-4 promotes apoptosis in a variety of cancerous cells, but not in normal cells. In this review, we focused on the structure, expression and function of Par-4 in apoptotic signaling pathway. Functional domains of Par-4 include two nuclear localization sequences (NLS), a leucine zipper (LZ) domain, a nuclear export sequence (NES) and selective for apoptosis in cancer cell (SAC) domain. Many studies have underlined the importance of Par-4 in preventing cancer development. The activity of Par-4 is differently regulated by localization of intracellular and extracellular Par-4. Intracellular Par-4 inhibits Akt- and NF-κB-mediated cell survival pathways and downregulates Bcl-2 expression. Extracellular Par-4 activates the extrinsic apoptotic pathway by binding to cell surface receptor GRP78, a stress response protein that is in the endoplasmic reticulum (ER). Endogenous Par-4 sensitizes cancer cells to various apoptotic stimuli, while exogenous Par-4 enhances SAC domain-dependent apoptosis in cancer cells, but not normal cells. Therefore, Par-4 is an attractive target for cancer therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.3667-3671
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• 2015

Invasion and metastasis is the major cause of tumor recurrence, difficulty for cure and low survival rate. Excavating key transcription factors, which can regulate tumor invasion and metastasis, are crucial to the development of therapeutic strategies for cancers. PU.1 is a master hematopoietic transcription factor and a vital regulator in life. Here, we report that, compared to adjacent non-cancerous tissues, expression of PU.1 mRNA in metastatic hepatocellular carcinoma (HCC), but not primary HCC, was significantly down-regulated. In addition, levels of PU.1 mRNA in metastatic hepatoma cell lines MHCC97L and MHCC97H were much lower than in non-metastatic Hep3B cells. Transwell invasion assays after PU.1 siRNA transfection showed that the invasion of hepatoma cell lines was increased markedly by PU.1 knockdown. Oppositely, overexpression of PU.1 suppressed the invasion of these cells. However, knockdown and overexpression of PU.1 did not influence proliferation. Finally, we tried to explore the potential mechanism of PU.1 suppressing hepatoma cell invasion. ChIP-qPCR analysis showed that PU.1 exhibited a high binding capacity with miR-615-5p promoter sequence. Overexpression of PU.1 caused a dramatic increase of pri-, pre- and mature miR-615-5p, as well as a marked decrease of miR-615-5p target gene IGF2. These data indicate that PU.1 inhibits invasion of human HCC through promoting miR-615-5p and suppressing IGF2. These findings improve our understanding of PU.1 regulatory roles and provided a potential target for metastatic HCC diagnosis and therapy.

• Molecular & Cellular Toxicology
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• v.3 no.3
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• pp.198-207
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• 2007

[ $^{18}F$ ]-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET) scan has been found to reflect tumor aggressiveness and prognosis in various types of cancer. In this study, the gene expression profiles of glial tumors were evaluated to determine whether glial tumors with high $^{18}F$-FDG uptake have more aggressive biological potential than with low uptake. Surgical specimens were obtained from the 12 patients with glial tumors (4 males and 8 females, age range 42-68 years). The tumor samples were divided into two groups based on the $^{18}F$-FDG uptake PET scan findings: high $^{18}F$-FDG uptake (n=4) and low $^{18}F$-FDG uptake (n=8). The pathological tumor grade was closely correlated with the $^{18}F$-FDG uptake pattern: Glial tumors with high $^{18}F$-FDG uptake were pathologically Edmondson-Steiner grade III, while those with low uptake were grade II. The total RNA was extracted from the frozen tissues of all glial tumors (n=12), and adjacent non-cancerous tissue (n=3). The gene expression profiles were evaluated using cDNA microarray. The glial tumors with high $^{18}F$-FDG uptake showed increase expression of 15 genes compared to those with low uptake (P<0.005). Nine genes were down-regulated. Gene expression is closely related to cell survival, cell-to-cell adhesion or cell spreading; therefore, glial tumors with high $^{18}F$-FDG uptake appear to have more aggressive biological properties than those with low uptake.

• International Journal of Oral Biology
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• v.36 no.3
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• pp.117-122
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• 2011

Endothelial cells are a vital constituent of most mammalian organs and are required to maintain the integrity of these tissues. These cells also play a major role in angiogenesis, inflammatory reactions, and in the regulation of thrombosis. Angiogenesis facilitates pulp formation and produces the vessels which are essential for the maintenance of tooth homeostasis. These vessels can also be used in bone and tissue regeneration, and in surgical procedures to place implants or to remove cancerous tissue. Furthermore, endothelial cell regeneration is the most critical component of the tooth generation process. The aim of the present study was to stimulate endothelial regeneration at a site of acute cyclophosphamide (CP)-induced endothelial injury by treatment with human umbilical cord-derived endothelial/mesenchymal stem cells (hEPCs). We randomly assigned 16 to 20-week-old female NOD/SCID mice into three separate groups, a hEPC ($1{\times}10^5$ cells) transplanted, 300mg/kg CP treated and saline (control) group. The mice were sacrificed on days 5 and 10 and blood was collected via the abdominal aorta for analysis. The alanine transaminase (ALT), aspartate aminotransferase (AST), serum alkaline phosphatase (s-ALP), and albumin (ALB) levels were then evaluated. Tissue sections from the livers and kidneys were stained with hematoxylin and eosin (HE) for microscopic analysis and were subjected to immunohistochemistry to evaluate any changes in the endothelial layer. CP treatment caused a weight reduction after one day. The kidney/body weight ratio increased in the hEPC treated animals compared with the CP only group at 10 days. Moreover, hEPC treatment resulted in reduced s-ALP, AST, ALT levels compared with the CP only group at 10 days. The CP only animals further showed endothelial injuries at five days which were recovered by hEPC treatment at 10 days. The number of CD31-positive cells was increased by hEPC treatment at both 5 and 10 days. In conclusion, the CP-induced disruption of endothelial cells is recovered by hEPC treatment, indicating that hEPC transplantation has potential benefits in the treatment of endothelial damage.