Wnt is a powerful signaling pathway that plays a crucial role in cell fate determination, survival, proliferation and motility during development, in adult tissues and cancer. The aims of the present study were three fold: i) to assess Wnt11 immunoexpression and its possible relationship with Wnt5a in high- and low-grade human serous ovarian cancer (HGSC and LGSC) specimens; ii) to assess Wnt11 expression levels in Wnt5a overexpressing SKOV-3 cells; iii) to reveal the role of Wnt11 in viability, adhesion, migration and invasion of SKOV-3 cells using recombinant human Wnt11 (rhWnt11). Immunohistochemistry revealed a significant difference in Wnt11 expression between HGSC and LGSC groups (p=0.001). Moreover, a positive correlation was observed between Wnt5a and Wnt11 expression in the HGSC (r=0.713, p=0.001), but not the LGSC group. The expression of Wnt11 was decreased by 35% in Wnt5a overexpressing cells (SKOV-3/Wnt5a) compared to mock controls. Similarly Wnt11 expression levels were decreased by 47% in the presence of exogenous Wnt5a compared to untreated cells. In the presence of rhWnt11, 31% increased cell viability (p<0.001) and 21% increased cell adhesion to matrigel (p<0.01) were observed compared to control. Cell migration was increased by 1.6-fold with rhWnt11 as revealed by transwell migration assay (p<0.001). However, 45% decreased cell invasion was observed in the presence of rhWnt11 compared to control (p<0.01). Our results may suggest that differential Wnt11 immunoexpression in HGSC compared to LGSC could play important roles in serous ovarian cancer progression and may be modulated by Wnt5a expression levels.
Cihan, Yasemin Benderli;Arslan, Alaettin;Cetindag, Mehmet Faik;Mutlu, Hasan
Asian Pacific Journal of Cancer Prevention
/
v.15
no.10
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pp.4225-4231
/
2014
Aim: To determine prognostic value of blood parameters on overall and progression-free survival in cases received adjuvant radiotherapy and chemotherapy with diagnosis of stage I-III breast cancer. Materials and Methods: We retrospectively reviewed files of 350 patients with non-metastatic breast cancer who were treated in the Radiation Oncology Department of Kayseri Teaching Hospital between 2005 and 2010. Pretreatment white blood cell (WBC), neutrophil, monocyte, basophil and eosinophil counts, and the neutrophil/lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR) were recorded. The relationship between clinicopathological findings and blood parameters was assessed. Results: Overall, 344 women and 6 men were recruited. Median age was $55.3{\pm}0.3$ years (range: 22-86). Of the cases, 243 (61.4%) received radiotherapy while 329 (94.3%), received chemotherapy and 215 (61.4%) received hormone therapy. Mean overall survival (OS) and progression-free survival (PFS) was 84.4 and 78.8 months, respectively. During follow-up, 48 patients died due to either disease-related or non-related causes. Local recurrence was detected in 14 cases, while distant metastasis was noted in 45 cases. In univariate analysis, age, pathology, perinodal invasion were significantly associated with overall survival, whereas gender, stage and hormone therapy were significantly associated with progression-free survival. In multivariate analysis, histopathological diagnosis (OR: 0.3; 95%: 0.1-0.7; p=0.006) and perinodal invasion (OR: 0.1; 95% CI: 0.1-1.3; p=0.026) were significantly associated with overall survival, whereas tumor stage (OR: 2.1; 95% CI: 0.0-0.7; p=0.014) and hormone therapy (OR: 2.1; 95%: 1.2-3.8; p=0.010) were significantly associated with progression-free survival. Conclusions: It was found that serum inflammatory markers including WBC, neutrophil, lymphocyte and monocyte counts, and NLR and PLR had no effect on prognosis in patients with breast cancer who underwent surgery and received adjuvant radiotherapy and chemotherapy.
Journal of the Korean Association of Oral and Maxillofacial Surgeons
/
v.37
no.6
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pp.490-495
/
2011
Introduction: Development of carcinoma on oral tongue may cause bilateral cervical lymph node metastasis, rapid invasion and growth of the cancer cells due to rich blood supply in muscle tissues. It is not only difficult to develop an animal experimental model, but also to proceed follow-up research after the development of such model as the induction of cancer lead to difficulty in taking nutrition for the experimental animals that often causes early death. Materials and Methods: IIn this study, author have transplanted YD-$10B_{mod}$ cells into nude mouse oral tongues with different cells number ($5{\times}10^4$, $5{\times}10^5$, $5{\times}10^6$ cells/mouse) and observed the development aspect of oral tongue cancers. Results: The cancer developed from orthotopic transplantation of YD-$10B_{mod}$ cells into nude mouse oral tongue show invasion and central necrosis of the tumor, similar to the cancers developed human oral tongue cancer. The difference in tumor size and the time of central necrosis development depending on the number of transplanted tumor cells shows the feasibility of extending the survival period of the nude mouse by limiting the transplanted tumor cells to < $5{\times}10^4$ cells/mouse or under per nude mouse. Conclusion: This nude mouse model could be used effectively in developing effective chemotheray agent and establishing an animal experimental model that can be used to study the mechanism of cervical lymph node metastasis of the oral tongue cancer.
Purpose: ${\alpha}$-fetoprotein (AFP)-producing gastric cancer is a rare tumor with high rates of liver metastasis and a poor prognosis. Many studies have been performed but there have been no comprehensive investigations of the clinicopathological and prognosis. Materials and Methods: Six hundred ninety four patients with gastric cancer who underwent a curative gastric resection in Hanyang University Hospital from February 2001 to December 2008 were evaluated retrospectively after excluding active or chronic hepatits, liver cirrhosis and preoperative distant metastasis. Among them, thirty five patients had an elevated serum level of AFP (>7 ng/ml) preoperatively. The clinicopathological features of AFP-producing gastric cancer were analyzed. Results: There was poorer differentiation, a higher incidence of lymph node metastasis, more marked lymphatic and vascular invasion in the AFP-positive group than in the AFP-negative group. The 5-year survival rate of the AFP-positive group was significantly poorer than that in the AFP-negative group (66% vs. 80%, P=0.002). A significantly higher incidence of liver metastasis was observed in the AFP-positive group than in the AFP-negative group (14.3% vs. 3.6%, P=0.002) with a shorter median time period from the operation to the metachronous liver metastasis (3.7 months vs. 14.1 months, P=0.043). Multivariate survival analysis revealed the depth of invasion, degree of lymph node metastasis and AFP-positivity to be the independent prognostic factors. Conclusions: AFP-producing gastric cancers have an aggressive behavior with a high metastatic potential to the liver. In addition, their clinicopathological features are quite different from the more common AFP-negative gastric cancer.
AMFR, autocrine motility factor receptor, also called gp78, is a cell surface cytokine receptor which has a dual role as an E3 ubiquitin ligase in endoplasmic reticulum-associated degradation. AMFR expression is associated with tumor malignancy. We here investigated the clinical significance of AMFR and its role in metastasis and prognosis in gastric cancer. Expression of AMFR, E-cadherin and N-cadherin in cancer tissues and matched adjacent normal tissues from 122 gastric cancer (GC) patients undergoing surgical resection was assessed by immunohistochemistry. Levels of these molecules in 17 cases selected randomly were also analysed by Western blotting. AMFR expression was significantly increased in gastric cancer tissues, and associated with invasion depth and lymph node metastasis. Kaplan-Meier analysis showed AMFR expression correlated with poor overall survival and an increased risk of recurrence in the GC cases. Cox regression analysis suggested AMFR to be an independent predictor for overall and recurrence-free survival. E-cadherin expression was decreased in gastric cancer tissues; conversely, N-cadherin was increased. Expression of AMFR negatively correlated with E-cadherin expression, whereas N-cadherin expression showed a significant positive correlation with AMFR expression. AMFR might be involved in the regulation of epithelial-mesenchymal transition, with aberrant expression correlating with a poor prognosis and promoting invasion and metastasis in GCs.
Purpose: The purpose of this study was to describe treatment patterns of radiotherapy (RT) for prostate cancer in Korea. Materials and Methods: A questionnaire about radiation treatment technique and principles in 2013 was sent to 83 radiation oncologists and data from 57 hospitals were collected analyzed to find patterns of RT for prostate cancer patients in Korea. Results: The number of patients with prostate cancer treated with definitive RT ranged from 1 to 72 per hospital in 2013. RT doses and target volumes increased according to risk groups but the range of radiation doses was wide (60 to 81.4 Gy) and the fraction size was diverse (1.8 to 5 Gy). Intensity-modulated radiation therapy was used for definitive treatment in 93.8% of hospitals. Hormonal therapy was integrated with radiation for intermediate (63.2%) and high risk patients (77.2%). Adjuvant RT after radical prostatectomy was performed in 46 hospitals (80.7%). Indications of adjuvant RT included positive resection margin, seminal vesicle invasion, and capsular invasion. The total dose for adjuvant RT ranged from 50 to 72 Gy in 24-39 fractions. Salvage RT was delivered with findings of consecutive elevations in prostate-specific antigen (PSA), PSA level over 0.2 ng/mL, or clinical recurrence. The total radiation doses ranged from 50 to 80 Gy with a range of 1.8 to 2.5 Gy per fraction for salvage RT. Conclusion: This nationwide patterns of care study suggests that variable radiation techniques and a diverse range of dose fractionation schemes are applied for prostate cancer treatment in Korea. Standard guidelines for RT in prostate cancer need to be developed.
At diagnosis, the majority of patients with gastric cancer are found to have local invasion or distant organ metastasis, even though the sole measure for a complete cure is a curative resection. A curative resection is hardly applicable for those with invasion and metastasis; thus, trials with neoadjuvant chemotherapy for downstaging the cancer should be considered. Docetaxel is a semisynthetic taxane that promotes tubulin polymerization and inhibits microtubule depolymerization. In recent studies, many metastatic gastric cancers were treated using neoadjuvant chemotherapy with docetaxel, and the response rates were reported. We report here two cases of locally advanced, non-resectable gastric cancer that were candidates for a curative resection after induction chemotherapy with docetaxel and cisplatin.
Purpose: The aims of this study were to evaluate the expression of the large tumor suppressor (LATS) genes LATS1 and LATS2 by immunohistochemical staining of gastric cancer, and to evaluate the clinicopathological significance of LATS expression and its correlation with overall survival (OS). Materials and Methods: LATS1 and LATS2 expression in a tissue microarray was detected by immunohistochemistry, using 264 gastric cancer specimens surgically resected between July 2006 and December 2009. Results: Low expression of LATS1 was significantly associated with more advanced American Joint Committee on Cancer (AJCC) stage (P=0.001) and T stage (P=0.032), lymph node (LN) metastasis (P=0.040), perineural invasion (P=0.042), poor histologic grade (P=0.007), and diffuse-type histology by the Lauren classification (P=0.033). Low expression of LATS2 was significantly correlated with older age (${\geq}65$, P=0.027), more advanced AJCC stage (P=0.001) and T stage (P=0.001), LN metastasis (P=0.004), perineural invasion (P=0.004), poor histologic grade (P<0.001), and diffuse-type histology by the Lauren classification (P<0.001). Kaplan-Meier survival analysis revealed significantly poor OS rates in the groups with low LATS1 (P=0.037) and LATS2 (P=0.037) expression. Conclusions: Expression of LATS1 or LATS2 is a significant marker for a good prognosis in patients with gastric cancer.
Jung, Hae Yoen;Cho, Hyundeuk;Oh, Mee-Hye;Lee, Ji-Hye;Lee, Hyun Ju;Jang, Si-Hyong;Lee, Moon Soo
Journal of Gastric Cancer
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v.15
no.1
/
pp.39-45
/
2015
Purpose: Recent studies have revealed recurrent alterations in the cell adhesion gene FAT4, a candidate tumor suppressor gene, in cancer. FAT atypical cadherin 4 (FAT4) is a transmembrane receptor involved in the Hippo signaling pathway, which is involved in the control of organ size. Here, we investigated the loss of FAT4 expression and its association with clinicopathological risk factors in gastric cancer. Materials and Methods: We assessed the expression of FAT4 by using immunohistochemistry on three tissue microarrays containing samples from 136 gastric cancer cases, radically resected in the Soonchunhyang University Cheonan Hospital between July 2006 and June 2008. Cytoplasmic immunoexpression of FAT4 was semi-quantitatively scored using the H-score system. An H-score of ${\geq}10$ was considered positive for FAT4 expression. Results: Variable cytoplasmic expressions of FAT4 were observed in gastric cancers, with 33 cases (24.3%) showing loss of expression (H-score <10). Loss of FAT4 expression was associated with an increased rate of perineural invasion (H-score <10 vs. ${\geq}10$, 36.4% vs. 16.5%, P=0.015), high pathologic T stage (P=0.015), high tumor-node-metastasis stage (P=0.017), and reduced disease-free survival time (H-score <10 vs. ${\geq}10$, mean survival $62.7{\pm}7.3$ months vs. $79.1{\pm}3.1$ months, P=0.025). However, no association was found between the loss of FAT4 expression and tumor size, gross type, histologic subtype, Lauren classification, lymphovascular invasion, or overall survival. Conclusions: Loss of FAT4 expression appears to be associated with invasiveness in gastric cancer.
Choi, Yong-Seok;Kim, Min Gyeong;Lee, Jong-Ho;Park, Joo-Yong;Choi, Sung-Weon
Journal of the Korean Association of Oral and Maxillofacial Surgeons
/
v.48
no.5
/
pp.284-291
/
2022
Objectives: This study aimed to analyze the clinicopathological prognostic factors affecting the survival of patients with oral squamous cell carcinoma (OSCC). Materials and Methods: A retrospective study was conducted on patients with OSCC who received treatment at the Oral Oncology Clinic of the National Cancer Center (NCC) from June 2001 to December 2020. The patients' sex, age, primary site, T stage, node metastasis, TNM staging, perineural invasion (PNI), lymphovascular invasion (LVI), differentiation, surgical resection margin, smoking, and drinking habits were investigated to analyze risk factors. For the univariate analysis, a Kaplan-Meier survival analysis and log-rank test were used. Additionally, for the multivariable analysis, a Cox proportional hazard model analysis was used. For both analyses, statistical significance was considered when P<0.05. Results: During the investigation period, 407 patients were received surgical treatment at the NCC. Their overall survival rate (OS) for five years was 70.7%, and the disease-free survival rate (DFS) was 60.6%. The multivariable analysis revealed that node metastasis, PNI, and differentiation were significantly associated with poor OS. For DFS, PNI and differentiation were associated with poor survival rates. Conclusion: In patients with OSCC, cervical node metastasis, PNI, and differentiation should be considered important prognostic factors for postoperative survival.
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