• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.1
• /
• pp.511-514
• /
• 2013

Background: A small but significant proportion of cases with atypical squamous cells of undetermined significance (ASCUS) may harbour CIN 2-3, or even invasive carcinoma. Although immediate colposcopy, HPV-DNA testing or expectant management are three recommended options in ASCUS triage, a consensus does not currently exist on which one of these approaches is the most efficient. In this study, we aimed to compare the performance and cost of immediate colposcopy and colposcopy based on the human papillomavirus (HPV) testing for detecting histologically confirmed high-grade cervical intraepithelial neoplasia (CIN) in women with ASCUS. Materials and Methods: Records of 594 women with an index Papanicolaou smear showing ASCUS were retrospectively analyzed. Women in the immediate colposcopy arm were referred directly to colposcopy (immediate colposcopy group, n=255) and those in the HPV triage arm were proceeded to colposcopy if the high-risk HPV (hrHPV) test was positive (HPV triage group, n=339). High grade CIN (CIN2+) detection rate and treatment costs were compared between the groups. Results: The detected rate of CIN2+ was higher in the HPV triage group compared to immediate colposcopy group (8% vs. 1.6%, p=0.011). In the HPV triage group, the total cost, cost per patient, and the cost for detecting one case of high grade CIN were higher than the immediate colposcopy group (p<0.001). Conclusions: In women with ASCUS cytology, HPV DNA testing followed by colposcopy is more costly than immediate colposcopy, but this approach is associated with a higher rate of CIN2+ detection. This findings suggest that HPV DNA testing combined with cervical cytology could reduce the referral rate to colposcopy.

• Tuberculosis and Respiratory Diseases
• /
• v.65 no.2
• /
• pp.105-109
• /
• 2008

Background: Fascin is an actin-bundling protein that plays an important role in cellular motility. Fascin is normally expressed in the neuronal and mesenchymal cells and its expression is low or absent in the epithelia. However, an overexpression of fascin has been linked to the invasive behavior of some neoplasms such as breast, stomach and ovarian tumors. In this study, we evaluated the expression of fascin and its prognostic significance in stage I non-small cell lung cancer (NSCLC). Methods: Immunohistochemical staining for fascin was performed on the paraffin-embeded tissue sections of 81 cases of resected NSCLC. Staining of more than 5% of the tumor cells was recorded as positive immunoreactivity. Results: Fascin expression was seen in 73% (59/81) of the cases and this was more frequently seen in squamous cell carcinoma than in adenocarcinoma (93% vs 42%). There were no significant correlations of fascin immunoreactivity with tumor recurrence and overall survival. Conclusion: The expression rate of fascin was relatively high in NSCLC, but this was without prognostic significance. The exact clinical role of fascin should be defined through further investigations.

• Journal of Gastric Cancer
• /
• v.1 no.1
• /
• pp.4-9
• /
• 2001

Purpose: The trefoil factor family 1 (TFF1) has a protective effect against gastric mucosal damage induced by nonsteroidal anti-inflammatory drugs or ethanol. In addition, a TFF1 knockout mouse model has exhibited circumferential adenomas with high-grade dysplasia, of which $30\%$ progressed into frankly invasive carcinomas. We tried to determine whether the expression pattern of the TFF1 could be involved in the development of sporadic gastric carcinomas. Materials and Methods: We examined TFF1 expression in a series of 43 sporadic gastric carcinomas and 18 gastric adenomas by immunohistochemistry. Results: Strong positive TFF1 staining was identified primarily in the normal gastric mucosa, mainly in the cytoplasm of the superficial and foveolar epithelium. We found TFF1 expression in $55.8\%$ (24 out of 43) of the gastric carcinomas and in $16.7\%$ (3 out of 18) of the gastric adenomas. Statistically, TFF1 immunoreactivity was significantly higher in diffuse-type ($82.4\%$) than in intestinal-type ($38.5\%$) carcinomas(p=0.0058, Fisher's exact test). Conclusion: Our findings provide sufficient evidence that the expression of TFF1 in gastric cancer may simply disclose gastric-type differentiation of neoplastic cells and provide further support for the existence of at least two pathways of malignant transformation of the gastric mucosa: one via intestinal metaplasia and adenomatous dysplasia, leading to glandular carcinomas with intestinal-type differentiation, and the other via hyperplastic changes or de novo changes, leading to diffuse carcinomas and to a subset of glandular carcinomas displaying gastric-type differentiation.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.11
• /
• pp.6261-6265
• /
• 2013

Background: Recent studies have suggested that expression of the RAS protein activator like-1 gene (RASAL1) is decreased in gastric carcinoma tissues and cell lines, indicated a role in tumorigenesis and development of gastric cancer. Reduced expression of RASAL1 could result in aberrant increase of activity of RAS signaling pathways in cancer cells. However, the exact mechanism which induces down-regulation of the RASAL1 gene remains unclear. This study aimed to determine the methylation status and regulation of RASAL1 in gastric cancer. Materials and Methods: Using the methylation-specific polymerase chain reaction (MSP), the methylation status of CpG islands in the RASAL1 promoter in gastric cancers and paired adjacent non-cancerous tissues from 40 patients was assessed and its clinicopathological significance was analyzed. The methylation status of RASAL1 in gastric cancer lines MKN-28, SGC-790l, BGC-823, as well as in normal gastric epithelial cell line GES-l was also determined after treatment with a DNA methyltransferase inhibitor, 5-aza-2'-doexycytidine (5-Aza-CdR). RAS activity (GAS-GTP) was assessed through a pull-down method, while protein levels of ERK1/2, a downstream molecule of RAS signaling pathways, were determined by Western blotting. Results: The frequencies of RASAL1 promoter methylation in gastric cancer and paired adjacent non-cancerous tissues were 70% (28/40) and 30% (12/40) respectively (P<0.05). There were significantly correlations between RASAL1 promoter methylation with tumor differentiation, tumor size, invasive depth and lymph node metastasis in patients with gastric cancer (all P<0.05), but no correlation was found for age or gender. Promoter hypermethylation of the RASAL1 gene was detected in MKN-28, SGC-790l and BGC-823 cancer cells, but not in the normal gastric epithelial cell line GES-1. Elevated expression of the RASAL1 protein, a decreased RAS-GTP and p-ERK1/2 protein were detected in three gastric cancer cell lines after treatment with 5-Aza-CdR. Conclusions: Aberrant hypermethylation of the RASAL1 gene promoter frequently occurs in gastric cancer tissues and cells. In addition, the demethylating agent 5-Aza-CdR can reverse the hypermethylation of RASAL1 gene and up-regulate the expression of RASAL1 significantly in gastric cancer cells in vivo. Our study suggests that RASAL1 promoter methylation may have a certain relationship with the reduced RASAL1 expression in gastric cancer.

• Asian Pacific Journal of Cancer Prevention
• /
• v.17 no.1
• /
• pp.249-254
• /
• 2016

Molecular detection methods such as RT-PCR for detecting breast cancer-associated gene expression in the peripheral blood have the potential to modify breast cancer (BC) staging and therapy. In this regard, we evaluated the potential of erb-B2 molecular marker in BC detection and analyzed the expression of erb-B2 mRNA in the peripheral blood and fresh tissue samples of 50 pretreated female BC patients and 50 healthy females by reverse transcription-PCR (RT-PCR) method. We also assessed the correlation of erb-B2 mRNA marker positivity in peripheral blood and tumor tissue samples with clinical and pathological factors in BC patients in order to evaluate its prognostic value. It was shown that there is a significant difference between healthy females and BC patients with expression of the erb-B2 molecular marker (p<0.01). A significant difference between the expression of erb-B2 in the peripheral blood and tissue samples of BC patients (p<0.01) and the frequency of circulating erb-B2 mRNA expression in peripheral blood and in tissue was detected by RT-PCR. No correlation was found between erb-B2 mRNA expression in blood or tumor tissue samples and lymph node, tumor grade, tumor stage, tumor size, patient's age, ki67, estrogen receptor (ER), progesterone receptor (PGR), P53, and HER-2 status. However, in a small subset of 31 BC patients we found that expression of erb-B2 in peripheral blood or in both peripheral blood and tumor tissue was directly correlated with lympho-vascular invasion and perineural invasion as poor prognostic features. The highest rates of erb-B2 expression in peripheral blood or tumor tissue were in the ER and PR negative and HER-2 positive group. This study suggests that the application of the RT-PCR and immunohistochemical methods for erb-B2 molecular marker detection would provide a higher detection rate, especially in early stage BC.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.9
• /
• pp.5287-5291
• /
• 2013

The human papilloma virus (HPV) causes skin and mucous membrane infections. It crosses from one person to another by skin-to-skin contact, such as sexual contact. There are more than 100 types of HPV that can influence different parts of the body. Some types of HPV can cause cancer (such as cervical or anal cancer) and others can cause warts (such as genital or plantar warts). HPV infection is one of the most common sexually transmitted infections (STIs) in Iran and around the world. Considerable molecular evidence suggests a role for human papilloma virus (HPV) in the pathogenesis of carcinoma. Epidemiological studies on human papilloma viruses (HPVs) infections in general population are critical for the performing of health policy guidelines for developing the strategies to hinder the primary and secondary different cancer. In different parts of Iran, there is a lack of population-based studies to determine the prevalence of HPV in the general population. The aim of this population-based study was therefore to report the prevalence ratse of HPV types among Iranian patients. To study the risk of human papilloma virus (HPV) infection, we managed a retrospective study in Kerman province, southeast of Iran. For this purpose, 410 patients tested for the presence of HPV DNA using PCR and INNo-Lipa assays. HPV DNA was detected in 108 out of 410 patients (26.34%), while it was not detected in any of the control group samples. Patients included 23 (21.1%) males and 86 (78.8%) females. HPV type 6 was the most common (49%) followed by HPV type 16 (10.1%), and also HPV type11 (9.2%). The prevalence of HPV in Iran is comparable to those reported in other regions of the world. In a similar manner, it seems that HPV types 6, 16 and11 are the most common types in Kerman. Additional studies on larger group of patients, particularly in those with pre-invasive forms of disease, are needed to explain the roles of different HPV types in this location of Iran.

• The Korean Journal of Nuclear Medicine Technology
• /
• v.12 no.1
• /
• pp.33-38
• /
• 2008

Purpose: The Gated cardiac blood pool scan is non-invasive method that a quantitative evaluation of left ventricular function. Also this scan have shown the value of radionuclide ejection fraction measurements during the course of chemotherapy as a predictor of cardiac toxicity. Therefore a reliable method of monitoring its cardiotoxic effects is necessary. the purpose of this study is to minimize the overestimate of left ventricular ejection fraction (LVEF) by modified body position to reduce the influence of scattered rays from surrounding organs of the heart in the background region of interest. Materials and Methods: Gated cardiac blood pool scan using in vivo $^{99m}Tc$-red blood cell (RBC) was carried out in 20 patients (mean $44.8{\pm}8.6$ yr) with chemotherapy for a breast carcinoma. Data acquisition requires about 600 seconds and 24 frames of one heart cycle by the multigated acquisition mode, Synchronization deteriorates toward the end of the cycle and with the distance from the trigger signal (R-wave) by ECG gating. Gated cardiac blood pool scan was studied with conventional method (supine position and the detector head in $30-45^{\circ}$ left anterior oblique position and caudal $10-20^{\circ}$ tilt) and compared with modified method (left lateral flexion position with 360 mL of drinking water). LVEF analysis was performed by using the automatically computer mode. Results: The ROI counts of modified scan method were lower than LV conventional method ($1429{\pm}251$ versus $1853{\pm}243$, <0.01). And LVEF of modified method was also decrease compared with conventional method ($58.3{\pm}5.6%$ versus $65.3{\pm}6.1%$, <0.01). Imaging analysis indicated that stomach was expanded because of water and spleen position was changed to lateral inferior compared with conventional method. Conclusion: This study shows that the modified method in MUGA reduce the influence of scattered rays from surrounding organs. Because after change the body position to left lateral flexion and drinking water, the location of spleen, left lobe of liver and stomach had changed and they could escaped from background ROI. Therefore, modified method could help to minimize the overestimate LVEF (%).

• Molecules and Cells
• /
• v.41 no.5
• /
• pp.423-435
• /
• 2018

This investigation was aimed at working out the combined role of lncRNA H19, miR-29b and Wnt signaling in the development of colorectal cancer (CRC). In the aggregate, 185 CRC tissues and corresponding para-carcinoma tissues were gathered. The human CRC cell lines (i.e. HT29, HCT116, SW480 and SW620) and normal colorectal mucosa cell line (NCM460) were also purchased. Si-H19, si-NC, miR-29b-3p mimics, miR-29b-3p inhibitor, si-PGRN and negative control (NC) were, respectively, transfected into the CRC cells. Luciferase reporter plasmids were prepared to evaluate the transduction activity of $Wnt/{\beta}-catenin$ signaling pathway, and dual-luciferase reporter gene assay was arranged to confirm the targeted relationship between H19 and miR-29b-3p, as well as between miR-29b-3p and PGRN. Finally, the proliferative and invasive capacities of CRC cells were appraised through transwell, MTT and scratch assays. As a result, overexpressed H19 and down-expressed miR-29b-3p displayed close associations with the CRC patients' poor prognosis (P < 0.05). Besides, transfection with si-H19, miR-29b-3p mimic or si-PGRN were correlated with elevated E-cadherin expression, decreased snail and vimentin expressions, as well as less-motivated cell proliferation and cell metastasis (P < 0.05). Moreover, H19 was verified to directly target miR-29b-3p based on the luciferase reporter gene assay (P < 0.05), and miR-29b-3p also bound to PGRN in a direct manner (P < 0.05). Finally, addition of LiCl ($Wnt/{\beta}-catenin$ pathway activator) or XAV93920 ($Wnt/{\beta}-catenin$ pathway inhibitor) would cause remarkably altered E-cadherin, c-Myc, vimentin and snail expressions, as well as significantly changed transcriptional activity of ${\beta}-catenin/Tcf$ reporter plasmid (P < 0.05). In conclusion, the lncRNA H19/miR-29b-3p/PGRN/Wnt axis counted a great deal for seeking appropriate diagnostic biomarkers and treatment targets for CRC.

• Journal of the Korea Academia-Industrial cooperation Society
• /
• v.12 no.9
• /
• pp.4068-4074
• /
• 2011

The purpose of this study was to examine the usefulness of MR Breast perfusion image and time-signal intensity curve in patients diagnosed with breast cancer. We selected on 20 patients who were histologically diagnosed to have invasive ductal carcinoma (IDC) from March 2009 to December 2010. First, the Breast perfusion mapping image was reconstructed after obtaining the dynamic contrast enhancement image. The reconstructed image measured the slope, maximal relative enhancement, and time to peak on the detail including the lesion region, normal region, back ground region after obtaining the time-signal intensity curve. The lesion region and normal and slope of the back ground part were measured with the quantitive analytical method about the research and the average was compared and was analyze. In the qualitative analysis, the signal strength of each pixel was analyze with the macroscopic and being high it was low, the medium (2) performed the division of (a) by the three-point standard and the average was measured. The findings from the quantitative image analysis are the following: In the lesion region, the slope and maximal relative enhancement were the highestest among and the time to peak was the highestest in the back ground region. In the qualitative analysis, the breast perfusion image showed a diagnostic efficiency.

• Journal of Breast Cancer
• /
• v.21 no.4
• /
• pp.406-414
• /
• 2018

Purpose: T-cell immunoglobulin and mucin domain-containing molecule 3 (TIM-3) is an emerging immune response molecule related to T-cell anergy. There has been tremendous interest in breast cancer targeting immune checkpoint molecules, especially in the triple-negative breast cancer (TNBC). This study was designed to investigate TIM-3 expression on tumor infiltrating lymphocytes (TILs), its relationships with clinicopathological parameters and expression of programmed death receptor 1 (PD-1)/programmed death receptor ligand 1 (PD-L1), and its prognostic role. Methods: Immunohistochemistry on tissue microarray blocks produced from 109 samples of invasive ductal carcinoma type TNBC was performed with antibodies toward TIM-3, PD-1, PD-L1 and breast cancer-related molecular markers. Associations between their expression and clinicopathological parameters as well as survival analyses were performed. Results: TIM-3 was expressed in TILs from all 109 TNBCs, consisting of 17 cases (<5%), 31 cases (6%-25%), 48 cases (26%-50%), and 13 cases (>51%). High TIM-3 was significantly correlated with younger patients (p=0.0101), high TILs (p=0.0029), high tumor stage (p=0.0018), high PD-1 (p=0.0001) and high PD-L1 (p=0.0019), and tended to be associated with higher histologic grade, absence of extensive in situ components and microcalcification. High TIM-3 expression was significantly associated with a combinational immunophenotype group of high PD-L1 and high PD-1 (p<0.0001). High TIM-3 demonstrated a significantly better disease-free survival (DFS) (p<0.0001) and longer overall survival (OS) (p=0.0001), together with high TILs and high PD-1. In univariate survival analysis, high TIM-3 showed reduced relapse risk (p<0.0001) and longer OS (p=0.0003), together with high PD-1 expression. In multivariate analysis, high TIM-3 was statistically significant in predicting prognosis, showing better DFS (hazard ratio [HR], 0.0994; 95% confidence interval [CI], 0.0296-0.3337; p=0.0002) and longer OS (HR, 0.1109; 95% CI, 0.0314-0.3912; p=0.0006). Conclusion: In this study, we demonstrate that TIM-3 expression is an independent positive prognostic factor in TNBC, despite its association with poor clinical and pathologic features.