• Asian Pacific Journal of Cancer Prevention
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• v.14 no.8
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• pp.4549-4552
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• 2013

The incidence of gastric cancer worldwide, and in particular in developing countries, has shown a marked increase. Poor prognosis of gastric cancer patients occurs due to the rapid metastasis of the disease via the lymphatic and blood vessels. The aim of this study was to investigate the expression and the clinical significance of D2-40 and CD34 in human gastric cancer. D2-40 and CD34 expression wasdetected in 1,072 cases of Chinese patients with gastric carcinoma using immunohistochemistry. The lymphatic vessel density (LVD) and microvessel density (MVD) were calculated and analyzed and the correlation with the clinicopathological factors and prognosis was determined. The LVD and MVD of the gastric cancer cases were significantly higher compared to those of normal tissues (P < 0.05). The expression of D2-40-LVD and CD34-MVD in the malignancies were positively related to the age, tumor size, invasion depth, lymphatic metastasis and pathological tumor-node-metastasis (pTNM) (P < 0.05); However, no statistically significant difference was identified between them with the patient gender (P > 0.05). Up-regulation of D2-40 and CD34 expression was significantly correlated with the poor survival rate in univariate and multivariate analyses. The LVD marked by D2-40 and the MVD marked by CD34 were positively correlated to the clinicopathological factors of the malignancies and may play important role in the development and progression of gastric cancer.

• Journal of Physiology & Pathology in Korean Medicine
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• v.38 no.1
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• pp.32-37
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• 2024

The aim of this study was to investigate the role of Daesiho-tang (Da Chai Hu-Tang) water extract (DSTE) in regulating chronic stress-induced cancer progression, focusing on its activity in modulating tumor-associated macrophages (TAMs). Different stimuli can polarize TAMs into immune-stimulating M1 macrophages or immunosuppressive M2 macrophages. During cancer progression, M2 phenotype increases and supports tumor growth, angiogenesis and metastasis. Notably, chronic stress-induced catecholamines promote M2 macrophage polarization. In this study, we investigated whether DSTE regulates norepinephrine (NE)-induced M2 macrophage polarization in RAW 264.7 mouse macrophage cells. Even though NE itself did not increase the expression of M2 markers, the conditioned media of NE-treated 4T1 mouse breast cancer cells (NE CM) significantly up-regulated M2 markers in RAW 264.7 cells, suggesting that NE-regulated cancer cell secretome stimulated M2 polarization. However, such increase was abrogated by DSTE. NE CM also induced phosphorylation of signal transducer and activator of transcription 6 (STAT6) in RAW 264.7 cells, which was clearly reversed by pretreatment with DSTE, demonstrating that DSTE inhibited M2 polarization by inactivating STAT6. Finally, M2-polarized RAW264.7 cells by NE CM markedly increased the migration of 4T1 cells. However, such increase was completely reversed by co-treating RAW264.7 cells with NE CM and DSTE, indicating that DSTE attenuated cancer cell migration by blocking M2 polarization. Taken together, our results suggest a probable use of DSTE for cancer patients under chronic stress by regulating M2 macrophage polarization.

• International journal of thyroidology
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• v.11 no.2
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• pp.143-151
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• 2018

Background and Objectives: Sirtuins (SIRTs) play important roles in cellular and organismal homeostasis. They have distinct gene expression patterns in various cancers; however, the relationship between SIRT expression and the progression of thyroid cancer is unclear. We investigated the expression of SIRTs in patients with papillary thyroid carcinoma (PTC) and their role as biomarkers for predicting the aggressiveness of this disease. Materials and Methods: We used immunohistochemical staining to evaluate the expression of SIRT1 and SIRT3 in tumor specimens from 270 patients with PTC. We also evaluated the potential association between SIRT expression and diverse clinicopathological features. Results: High SIRT1 expression was negatively correlated with lymphovascular invasion, central lymph node metastasis, and lateral lymph node metastasis. Multivariate analyses revealed that high SIRT1 expression was a negative independent risk factor for lateral lymph node metastasis. By contrast, high SIRT3 expression was positively correlated with locoregional recurrence. Interestingly, when patients were grouped by tumor SIRT expression patterns, the group with low SIRT1 expression and high SIRT3 expression was correlated with more aggressive cancer phenotypes including central lymph node metastasis and lateral lymph node metastasis. Conclusion: Our results suggest that SIRTs play dual roles in tumor progression, and the combination of decreased SIRT1 expression and increased SIRT3 expression is significantly associated with a poor prognosis in patients with PTC.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.5619-5624
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• 2015

Pancreatic cancer is a fatal malignancies which is predominantly seen in men and at advanced age (40-85 years) and has an aggressive course. Its frequency is gradually increasing over the past years. It accounts for 2% of all cancers and 5% of cancer-related deaths. Pancreatic cancer takes the first place among asymptomatic cancers. Ninety percent of cases are adenocarcinomas. Ten percent of the patients have a familial disposition. The disease is very difficult to detect as it has no early signs and spreads rapidly to surrounding organs is one of the most deadly types of cancer. Pancreatic cancer may result from hereditary germline or somatic acquired mutations in cancer-related genes and mutations also cause cancer progression and metastasis.

• Biomolecules & Therapeutics
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• v.26 no.1
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• pp.69-80
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• 2018

Cancer cells reprogram cellular metabolism to support the malignant features of tumors, such as rapid growth and proliferation. The cancer promoting effects of metabolic reprogramming are found in many aspects: generating additional energy, providing more anabolic molecules for biosynthesis, and rebalancing cellular redox states in cancer cells. Metabolic pathways are considered the pipelines to supply metabolic cofactors of epigenetic modifiers. In this regard, cancer metabolism, whereby cellular metabolite levels are greatly altered compared to normal levels, is closely associated with cancer epigenetics, which is implicated in many stages of tumorigenesis. In this review, we provide an overview of cancer metabolism and its involvement in epigenetic modifications and suggest that the metabolic adaptation leading to epigenetic changes in cancer cells is an important non-genetic factor for tumor progression, which cooperates with genetic causes. Understanding the interaction of metabolic reprogramming with epigenetics in cancers may help to develop novel or highly improved therapeutic strategies that target cancer metabolism.

• Journal of Digestive Cancer Reports
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• v.8 no.1
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• pp.51-55
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• 2020

Prognosis of patients with pancreatic cancer is poor due to difficulty in early diagnosis and low resectability rate at the time of diagnosis. Apart from the progression of cancer, venous thromboembolism - a complication that can increase patient mortality - is known to occur frequently in pancreatic cancer. This review was aimed at identifying whether venous thromboembolism is more common in pancreatic cancer than in other cancer types. In addition, we reviewed several studies to determine whether thromboprophylaxis increases the survival rates of patients with pancreatic cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.2019-2025
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• 2016

Hepatocellular carcinoma (HCC) is major health problem with high mortality rates, especially in patients with hepatitis B virus (HBV) infection. Telomerase function is one of common mechanisms affecting genome stability and cancer development. Recent studies demonstrated that genetic polymorphisms of telomerase associated genes such as telomerase associated protein 1 (TEP1) rs1713449 and PIN2/TERF1-interacting telomerase inhibitor 1 (PINX1) rs1469557 may be associated with risk of HCC and other cancers. In this study, 325 patients with HCC and 539 non-HCC groups [193 healthy controls, 80 patients with HBV-related liver cirrhosis (LC) and 266 patients with HBV-related chronic hepatitis (CH)] were enrolled to explore genetic polymorphisms of both SNPs using the allelic discrimination method based on MGB probe TaqMan real time PCR. We demonstrated that all genotypes of both genes were in Hardy-Wienberg equilibrium (P>0.05). Moreover, there was no significant association between rs1713449 genotypes and HCC risk, HCC progression and overall survival (P>0.05). Interestingly, we observed positive association of rs1469557 with risk of HCC when compared with the LC group under dominant (CC versus CT+TT, OR=1.89, 95% CI= 1.06-3.40, P=0.031) and allelic (C versus T alleles, OR=1.75, 95% CI=1.04-2.94, P=0.033) models, respectively. Moreover, overall survival of HCC patients with CC genotype of rs1469557 was significantly higher than non-CC genotype (Log-rank P=0.015). These findings suggest that PINX1 rs1469557 but not TEP1 rs1469557 might play a role in HCC progression in Thai patients with LC and be used as the prognosis marker to predict overall survival in HCC patients.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.2
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• pp.487-492
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• 2012

Trace element zinc deficiency or excess is implicated in the development or progression of some cancers. The exact role of zinc in the etiology of colon cancer is unclear. To cast light on this question, an experimental model of colon carcinogenesis was applied here. Six week old rats were given sub cutaneous injections of DMH (30 mg/kg body weight) twice a week for three months and sacrificed after 4 months (precancer model) and 6 months (cancer model). Plasma zinc levels showed a significant decrease (p<0.05) at 4 months and a greater significant decrease at 6 months (p<0.01) as compared with controls. In the large intestine there was a significant decrease in tissue zinc levels (p<0.005) and in CuZnSOD, and alkaline phosphatase activity (p<0.05) in the pre-cancerous model and a greater significant decrease in tissue zinc (p<0.0001), and in CuZnSOD and alkaline phosphatase activity (p<0.001), in the carcinoma model. The tissue zinc levels showed a significant decrease in the small intestine and stomach (p<0.005) and in liver (p<0.05) in the cancer model. 87% of the rats in the precancer group and 92% rats in the cancer group showed histological evidence of precancerous lesions and carcinomas respectively in the colon mucosa. This study suggests that the decrease in plasma zinc, tissue zinc and activity of zinc related enzymes are associated with the development of preneoplastic lesions and these biochemical parameters further decrease with progression to carcinoma in the colon.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10273-10276
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• 2015

Objective: To explore the clinical effects of nimotuzumab combined with chemotherapy in the treatment of late gastric cancer. Methods: A total of 34 reoccurrence or metastatic patients with late stage gastric cancer who were confirmed by histopathology and/or cytology were selected and randomly divided into observational and control groups, of 17 cases each. Patients in the control group were treated with the standard DCF plan, while patients in observational group additionally received nimotuzumab. The short-term and long-term efficacy and adverse reactions in the 2 groups were followed. Results: The objective response rate (ORR) and disease control rate (DCR) were 64.7% (11/17) and 82.4% (14/17) in observational group and 25.0%(4/16) and 37.5%(6/16) in the control group(ORR and DCR between 2 groups, ${\chi}^2=5.2412$, P=0.0221 and ${\chi}^2=6.9453$, P=0.0084). The median progression-free survival (PFS) time and median overall survival (OS) time were 6.50 months and 12.50 months in observational group and 4.50 months and 8.25 months in the control group (P=0.0212; P=0.0255). The main toxic and side effects in the 2 groups were reduced leukocytes and hemoglobin, gastrointestinal reactions and hair loss and these were relieved after symptomatic treatment and nutrition support therapy. There were no differences in the occurrence of toxic and side effects between the 2 groups. Conclusions: Nimotuzumab combined with DCF plan is effective in treating late stage gastric cancer. A larger scale study is now warranted for confirmation of the findings.

• Journal of Gastric Cancer
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• v.14 no.3
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• pp.147-155
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• 2014

Homeostatic imbalance between cell proliferation and death in gastric mucosal epithelia may lead to gastritis and gastric cancer. Despite abundant gastrokine 1 (GKN1) expression in the normal stomach, the loss of GKN1 expression is frequently detected in gastric mucosa infected with Helicobacter pylori, as well as in intestinal metaplasia and gastric cancer tissues, suggesting that GKN1 plays an important role in gastric mucosal defense, and the gene functions as a gastric tumor suppressor. In the stomach, GKN1 is involved in gastric mucosal inflammation by regulating cytokine production, the nuclear factor-${\kappa}B$ signaling pathway, and cyclooxygenase-2 expression. GKN1 also inhibits the carcinogenic potential of H. pylori protein CagA by binding to it, and up-regulates antioxidant enzymes. In addition, GKN1 reduces cell viability, proliferation, and colony formation by inhibiting cell cycle progression and epigenetic modification by down-regulating the expression levels of DNMT1 and EZH2, and DNMT1 activity, and inducing apoptosis through the death receptor-dependent pathway. Furthermore, GKN1 also inhibits gastric cancer cell invasion and metastasis via coordinated regulation of epithelial mesenchymal transition-related protein expression, reactive oxygen species production, and PI3K/Akt signaling pathway activation. Although the modes of action of GKN1 have not been clearly described, recent limited evidence suggests that GKN1 acts as a gastricspecific tumor suppressor. This review aims to discuss, comment, and summarize the recent progress in the understanding of the role of GKN1 in gastric cancer development and progression.