• Asian Pacific Journal of Cancer Prevention
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• v.16 no.10
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• pp.4317-4321
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• 2015

Background: Prognostic biomarkers in breast cancer are routinely investigated in the primary tumors to guide further management. However, it is proposed that the expression may change during the disease progression, and may result in a different immune profile in the metastatic nodes. This work aimed to investigate the expression of breast prognostic biomarkers in primary tumors and in its axillary nodal metastasis, to estimate the possible discordant expression. Materials and Methods: 60 paired primary and axillary nodal metastasis samples were collected from patients with primary breast cancer with positive nodal deposits, diagnosed at the Maadi Military Hospital, Cairo, Egypt, during the year 2013. ER, PR and HER2 expression was assessed by immunohistochemistry in all samples Results: 48.3% of the included cases showed concordant results for both ER and PR receptors between the primary tumor and its nodal metastasis while 51.7% showed discordant results and the discordance level was statistically significant. On the other hand, 70% of the cases showed concordant Her2 results between the primary tumors and the nodal deposits, 30% showed discordant results and the difference was significant. Conclusions: The study indicated that the discordance in ER and PR receptor expression between the primary breast tumor and their nodal metastasis may be significant. The possible switch in the biomarker status during the disease progression is worth noting and may change the patient therapeutic planning. So, whether the treatment selection should be based on biomarkers in the lymph node is a topic for further studies and future clinical trials.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.2229-2234
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• 2012

Purpose: To assess efficacy of Ki67 combined with VEGF as a molecular grading model to predict outcomes with non-muscle invasive bladder cancer (NMIBC). Materials: 72 NMIBC patients who underwent transurethral resection (TUR) followed by routine intravesical instillations were retrospectively analyzed in this study. Univariate and multivariate analyses were performed to confirm the prognostic values of the Ki67 labeling index (LI) and VEGF scoring for tumor recurrence and progression. Results: The novel molecular grading model for NMIBC contained three molecular grades including mG1 (Ki67 $LI{\leq}25%$, VEGF $scoring{\leq}8$), mG2 (Ki67 LI>25%, VEGF $scoring{\leq}8$; or Ki67 $LI{\leq}25%$, VEGF scoring > 8), and mG3 (Ki67 LI > 25%, VEGF scoring > 8), which can indicate favorable, intermediate and poor prognosis, respectively. Conclusions: The described novel molecular grading model utilizing Ki67 LI and VEGF scoring is helpful to effectively and accurately predict outcomes and optimize personal therapy.

• Radiation Oncology Journal
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• v.32 no.2
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• pp.63-69
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• 2014

Purpose: To find the applicability of adjuvant radiotherapy for extrahepatic bile duct cancer (EBDC), we analyzed the pattern of failure and evaluate prognostic factors of locoregional failure after curative resection without adjuvant treatment. Materials and Methods: In 97 patients with resected EBDC, the location of tumor was classified as proximal (n = 26) and distal (n = 71), using the junction of the cystic duct and common hepatic duct as the dividing point. Locoregional failure sites were categorized as follows: the hepatoduodenal ligament and tumor bed, the celiac artery and superior mesenteric artery, and other sites. Results: The median follow-up time was 29 months for surviving patients. Three-year locoregional progression-free survival, progression-free survival, and overall survival rates were 50%, 42%, and 52%, respectively. Regarding initial failures, 79% and 81% were locoregional failures in proximal and distal EBDC patients, respectively. The most common site was the hepatoduodenal ligament and tumor bed. In the multivariate analysis, perineural invasion was associated with poor locoregional progression-free survival (p = 0.023) and progression-free survival (p = 0.012); and elevated postoperative CA19-9 (${\geq}37U/mL$) did with poor locoregional progression-free survival (p = 0.002), progression-free survival (p < 0.001) and overall survival (p < 0.001). Conclusion: Both proximal and distal EBDC showed remarkable proportion of locoregional failure. Perineural invasion and elevated postoperative CA19-9 were risk factors of locoregional failure. In these patients with high risk of locoregional failure, adjuvant radiotherapy could be considered to improve locoregional control.

• Molecules and Cells
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• v.41 no.7
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• pp.653-664
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• 2018

The RNA-binding protein tristetraprolin (TTP) binds to adenosine-uridine AU-rich elements in the 3'-untranslated region of messenger RNAs and facilitates rapid degradation of the target mRNAs. Therefore, it regulates the expression of multiple cancer and immunity-associated transcripts. Furthermore, a lack of TTP in cancer cells influences cancer progression and predicts poor survival. Although the functions of TTP on cancer cells have previously been researched, the mechanism of TTP on the interaction between cancer cells with their micro-environment remains undiscovered. In this study, we admed to determine the role of cancer cell TTP during the interaction between tumor and immune cells, specifically regulatory T cells (Tregs). We evaluate the capability of TTP to modulate the antitumor immunity of GC and explored the underlying mechanism. The overexpression of TTP in GC cells dramatically increased peripheral blood mononuclear lymphocyte (PBML) -mediated cytotoxicity against GC cells. Increased cytotoxicity against TTP-overexpressed GC cells by PBMLs was determined by Treg development and infiltration. Surprisingly, we found the stabilization of programmed death-ligand 1 (PD-L1) mRNA was declining while TTP was elevated. The PD-L1 protein level was reduced in TTP-abundant GC cells. PD-L1 gas been found to play a pivotal role in Treg development and functional maintenance in immune system. Taken together, our results suggest the overexpression of TTP in GC cells not only affects cell survival and apoptosis but also increases PBMLs -mediated cytotoxicity against GC cells to decelerate tumor progression. Moreover, we identified PD-L1 as a critical TTP-regulated factor that contributes to inhibiting antitumor immunity.

• Proceedings of the Korean Society of Toxicology Conference
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• 2002.11b
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• pp.118-130
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• 2002

The frequency of prostate cancer has been increasing (1). Afflicting 10% of men older than the age of 65, it repre-sents the most frequently diagnosed cancer in American men, with an even higher incidence in the African-American population. Many investigators have tried to identify prognostic markers that distinguish indolent versus aggressive forms of prostate cancer, and to understand the genetic factors that evoke prostate cancer initiation and progression (2).(omitted)

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3899-3903
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• 2012

B7-H3 is a newly discovered member of the B7/CD28 superfamily which functions as an important T-cell immune molecule. It has been reported recently that B7-H3 is highly expressed in many cancer cells, the data indicating that it may be a regulation factor contributing to tumor-resistance. In our study, we used bioinformatics to identify differentially expressed genes between colonic cancer cells and normal colonic cells, aiming to analyze mechanisms and identify sub-pathways closely related to progression, with the final aim of finding small molecule drugs which might interfere this progression. We found that ajmaline is one related factor which may enhance self-immunity in colon carcinoma therapy and B7-H3 plays important roles with regard to immunoreactions of colonic cancer cells. All the results indicate that H7-B3 is a favorable prognostic biomarker for colon carcinomas, providing novel information regarding likely targets for intervention.

• Journal of Microbiology and Biotechnology
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• v.11 no.5
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• pp.876-879
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• 2001

${\gamma}$ -Tubulin is an essential component involved in microtubule nucleation. The present work examined whether the fast proliferation of cancer cells can be retarded by the depletion of ${\gamma}$ -tubulin expression. Two different gastric cancer cell lines and one control cell line were treated with antisence oligonucleotides complementary to the messenger RNA of ${\gamma}$ -tubulin. The$[^3H]$ -thymidine incorporation in the two gastric cancer cell lines, SNU-1 and SNU-216, was dramatically reducd by treatment with the ${\gamma}$ -tubulin antisense oligonucleotides in a dosage-dependent manner. In contrast, the control cell line, NIH/3T3, showed no significant effect from the antisense oligonucleotides even at a high concentration. The ablation of ${\gamma}$ -tubulin expression in the tumor cells resulted in an altered DNA synthesis during mitosis and it decreased the cell progression. Accordingly, the use of antisense oligonucleotides may be an effective way of inhibiting the proliferation of human gastric cancers.

• Journal of Gastric Cancer
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• v.20 no.3
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• pp.300-312
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• 2020

Purpose: Circular RNAs (circRNAs) are a new class of RNA molecules whose function is largely unknown. There is a growing evidence that circRNAs play an important regulatory role in the progression of a variety of human cancers. However, the exact roles and the mechanisms of circRNAs in gastric cancer are not clear. In this study, we aimed to elucidate the mechanism of hsa_circ_0005556. Materials and Methods: Real-time quantitative polymerase chain reaction was used to detect the expression of hsa_circ_0005556, miR-4270, and matrix metalloproteinase-19 (MMP19) in gastric cancer tissues and cell lines. The expression of hsa_circ_0005556 in gastric cancer cells was silenced by lentivirus, and cell proliferation, invasion, migration, and tumorigenesis in nude mice were assessed to evaluate the function of hsa_circ_0005556 in gastric cancer. Results: The expression of hsa_circ_0005556 in gastric cancer tissues and gastric cancer cell lines was higher compared to normal controls. In vitro, the downregulation of hsa_ circ_0005556 significantly inhibited proliferation, migration, and invasion of gastric cancer cells. In vivo, the downregulation of hsa_circ_0005556 suppressed tumor growth in nude mice. Conclusions: Our study shows that the hsa_circ_0005556/miR-4270/MMP19 axis is involved in proliferation, migration, and invasion of gastric cancer cells through the competing endogenous RNA (ceRNA) mechanism.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.22
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• pp.9945-9948
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• 2014

Background: The purpose of this study was to investigate Tim-3 expression on peripheral CD3-CD56+ natural killer (NK) cells and CD3+CD56+ natural killer T (NKT) cells in lung cancer patients. Materials and Methods: We analyzed Tim-3+CD3-CD56+ cells, Tim-3+CD3-$CD56^{dim}$ cells, Tim-3+CD3-$CD56^{bright}$ cells, and Tim-3+CD3+CD56+ cells in fresh peripheral blood from 79 lung cancer cases preoperatively and 53 healthy controls by flow cytometry. Postoperative blood samples were also analyzed from 21 members of the lung cancer patient cohort. Results: It was showed that expression of Tim-3 was significantly increased on CD3-CD56+ cells, CD3-$CD56^{dim}$ cells and CD3+CD56+ cells in lung cancer patients as compared to healthy controls (p=0.03, p=0.03 and p=0.04, respectively). When analyzing Tim-3 expression with cancer progression, results revealed more elevated Tim-3 expression in CD3-CD56+ cells, CD3-$CD56^{dim}$ cells and CD3+CD56+ cells in cases with advanced stages (III/IV) than those with stage I and II (p=0.02, p=0.04 and p=0.01, respectively). In addition, Tim-3 expression was significantly reduced on after surgical resection of the primary tumor (p<0.01). Conclusions: Tim-3 expression in natural killer cells from fresh peripheral blood may provide a useful indicator of disease progression of lung cancer. Furthermore, it was indicated that Tim-3 might be as a therapeutic target.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.12
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• pp.4881-4883
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• 2015

A population-based relationship between low vitamin D status and increased cancer risk is now generally accepted. However there were only few studies reported on prognostic impact. To determine the effect of low vitamin D on progression of breast cancer, we conducted a cross-sectional analysis of vitamin D levels and clinico-pathological characteristics in 200 cases of breast cancer diagnosed during 2011-2012 at the National Cancer Institute of Thailand. Vitamin D levels were measured by high-performance liquid chromatography (HPLC). Clinical and pathological data were accessed to examine prognostic effects of vitamin D. We found that the mean vitamin D level was $23.0{\pm}6.61ng/ml$. High vitamin D levels (${\geq}32ng/ml$) were detected in 7% of patients, low levels (<32 ng/ml) in 93% Mean vitamin D levels for stages 1-4 were $26.1{\pm}6.35$, $22.3{\pm}6.34$, $22.2{\pm}6.46$ and $21.3{\pm}5.42ng/ml$ respectively (P=0.016) and 24.1 and 21.3 ng/ml for lymph node negative and positive cases (P=0.006). Low vitamin D level (<32 ng/ml) was significantly found in majority of cases with advanced stage of the disease (P=0.036), positive node involvement (P=0.030) and large tumors (P=0.038). Our findings suggest that low and decreased level of vitamin D might correlate with progression and metastasis of breast cancer.