• The Korean Journal of Cytopathology
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• v.7 no.1
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• pp.97-102
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• 1996

Fine needle aspiration cytology of a pulmonary mass was performed on a 51-year-old man who had a left testicular mass. Cytologic features were composed of a homogeneous population of malignant cells associated with a background of foamy and lacelike material. The cellular features were characterized by monomorphous cell proliferation of relatively regular large cells, generally isolated or grouped. Occasionally, fine blanching stroma with large tumor cells and scanty lymphocytes were noted. The tumor cells had a round, regular nucleus, prominent round nucleoli, and a thin rim of cytoplasm containing large vacuoles or lacunae filled with glycogen. The fine needle aspiration cytologic diagnosis was highly consistent with metastatic seminoma from testis and less likely primary or other metastatic carcinoma. The diagnosis of resected testicular mass was classic seminoma. Despite the fact that cytopathologists were not familial with diagnosis of seminoma due to clinician's lack of interest in fine needle aspiration cytology of germ cell tumors including seminoma, it appears that a diagnosis of this tumor should not be problematic in cytologic material if specific histologic criteria are applied.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.4031-4036
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• 2012

Background: The negative signaling provided by interactions of the co-inhibitory molecule, programmed death-1 (PD-1), and its ligands, B7-H1 (PD-L1) and B7-DC (PD-L2), is a critical mechanism contributing to tumor evasion; blockade of this pathway has been proven to enhance cytotoxic activity and mediate antitumor therapy. Here we evaluated the anti-tumor efficacy of AAV-mediated delivery of the extracellular domain of murine PD-1 (sPD-1) to a tumor site. Material and Methods: An rAAV vector was constructed in which the expression of sPD-1, a known negative regulator of TCR signals, is driven by human cytomegalovirus immediate early promoter (CMV-P), using a triple plasmid transfection system. Tumor-bearing mice were then treated with the AAV/sPD1 construct and expression of sPD-1 in tumor tissues was determined by semi quantitative RT-PCR, and tumor weights and cytotoxic activity of splenocytes were measured. Results: Analysis of tumor homogenates revealed sPD-1 mRNA to be significantly overexpressed in rAAV/sPD-1 treated mice as compared with control levels. Its use for local gene therapy at the inoculation site of H22 hepatoma cells could inhibit tumor growth, also enhancing lysis of tumor cells by lymphocytes stimulated specifically with an antigen. In addition, PD-1 was also found expressed on the surfaces of activated CD8+ T cells. Conclusion: This study confirmed that expression of the soluble extracellular domain of PD-1 molecule could reduce tumor microenvironment inhibitory effects on T cells and enhance cytotoxicity. This suggests that it might be a potential target for development of therapies to augment T-cell responses in patients with malignancies.

• Natural Product Sciences
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• v.23 no.1
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• pp.21-28
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• 2017

In our program to search for new AMP-activated protein kinase (AMPK) activators from plants that exert potential anticancer property, we found that an EtOAc extract of Myristica fragrans (nutmeg) activated AMPK enzyme in human breast cancer MCF-7 cells. Two major diarylbutane-type lignans, macelignan and meso-dihydroguaiaretic acid (MDGA), were isolated as active principles from this extract. Treatment of breast cancer cells with two compounds induced cellular apoptosis, evidenced by cleavage of poly-(ADP-ribose) polymerase (PARP) and Ser 15 phosphorylation of p53. Moreover, macelignan and MDGA significantly inhibited the colony formation of MCF-7 breast cancer cells on soft agar. Intraperitoneal injection of macelignan and MDGA (20 mg/kg) suppressed the tumor growth of 4T1 mammary cancer cells. These results indicate that the chemopreventive effects of two major diarylbutane-type lignans from Myristica fragrans (nutmeg) may be associated with induction of apoptosis presumably through AMPK activation.

• Journal of Chest Surgery
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• v.37 no.8
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• pp.691-701
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• 2004

Background: Tissue hypoxia is a characteristic of many human malignant neoplasms, and hypoxia inducible factor-1 (HIF-1) plays a pivotal role in essential adaptive response to hypoxia, and activates a signal pathway for the expression of the hypoxia-regulated genes, resulting in increased oxygen delivery or facilitating metabolic adaptation to hypoxia. Increased level of HIF-1 a has been reported in many human malignancies, but in esophageal squamous cell carcinoma, the influence of HIF-1 a on tumor biology, including neovascularization, is not still defined. Material and Method: The influence of HIF-1 a expression on angiogenic factors, correlation between the tumor proliferation and HIF-1 a expression, interaction of HIF-1 a expression and p53, and correlation between HIF-1 a expression and clinicopathological prognostic parameters were investigated, using immunohistochemical stains for HIF-1 a, VEGF, CD34, p53, and Ki-67 on 77 cases of resected esophageal squamous cell carcinoma. Result: HIF-1 a expression in cancer cells was found in 33 of 77 esophageal squamous cell carcinoma cases. The 33 cases (42.9%) showed positive stain for HIF-1 a. High HIF-1 a expression was significantly associated with several pathological parameters, such as histologic grade (p=0.032), pathological TMN stage (p=0.002), the depth of tumor invasion (p=0.022), regional lymph node metastasis (p=0.002), distant metastasis (p=0.049), and lymphatic invasion (p=0.004). High HIF-1 a expression had significant VEGF immunoreactivity (p=0.008) and Ki-67 labeling index (p<0.001), but was not correlated with microvascular density within tumors (p=0.088). The high HIF-1 a expression was correlated with aberrant p53 accumulation with a marginal significance (p=0.056). The overall 5-year survival rate was 34.9%. The survival rate of patients with a high HIF-1 a expression was worse than that of patients with low-expression tumors (log-rank test, p=0.0001). High HIF-1 a expression was independent unfavorable factors although statistical significance is marginal in multivariate analysis. Conclusion: It is suggested that (1) high HIF-1 a expression in esophageal squamous cell carcinoma is associated with tumor hypoxia, or with genetic alteration in early carcinogenesis and progressive stages, (2) high HIF-1 a expression may be associated with intratumoral neovascularization through HIF-VEGF pathway, and (3) high HIF-1 a expression is associated with poor prognosis in patients with esophageal squamous cell carcinoma and may playa role as biomarker for regional lymph node metastasis.

• Journal of Chest Surgery
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• v.39 no.11 s.268
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• pp.828-837
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• 2006

Background: Tissue hypoxia is characteristic of many human malignant neoplasm, and hypoxia inducible factor-1(HIF-1) plays a pivotal role in essential adaptive response to hypoxia, and activates a signal pathway for the expression of the hypoxia-regulated genes, resulting in increasing $O_2$ delivery or facilitating metabolic adaptation to hypoxia. Increased level of HIF-$1{\alpha}$ has been reported in many human malignancies, but in non-small cell lung carcinoma the influence of HIF-$1{\alpha}$ on tumor biology, including neovascularization, is not still defined. In present study the relationship of HIF-$1{\alpha}$ expression on angiogenetic factors, relationship between the tumor proliferation and HIF-$1{\alpha}$ expression, interaction of HIF-$1{\alpha}$ expression and p53, and relationship between HIF-$1{\alpha}$ expression and clinico-pathological prognostic parameters were investigated. Material and Method: Archival tissue blocks recruited in this study were retrieved from fifty-nine patients with primary non-small cell lung carcinoma, who underwent pneumonectomy or lobectomy from 1997 to 1999. HIF-$1{\alpha}$, VEGF(vascular endothelial growth factor), and p53 protein expression and Ki-67 labeling index in tumor tissues were evaluated, using a standard avidin-biotin-peroxidase complex(ABC) immunohistochemistry. Relationship between the HIF-$1{\alpha}$ expression and VEGF, p53 overexpression and correlation between the HIF-$1{\alpha}$ expresseion and Ki-67 index were analyzed. Clinico-pathologic prognostic parameters were also analyzed. Result: HIF-$1{\alpha}$ expression in cancer cells was found in 24 of 59 cases of non-small cell lung carcinoma(40.7%). High HIF-$1{\alpha}$ expression was significantly associated with several pathological parameters, such as pathological TMN stage(p=0.004), pT stage(p=0.020), pN stage (p=0.029), and lymphovascular invasion(p=0.019). High HIF-$1{\alpha}$ expression was also significantly associated with VEGF immunoreactivity(p<0.001), and aberrant p53 expression(p=0.040). but was marginally associated with Ki-67 labeling index(p=0.092). The overall 5-year survival rate was 42.3%. The survival curve of patients with a high HIF-$1{\alpha}$ expression was worse than that of patients with low-expression(p=0.002). High HIF-$1{\alpha}$ expression was independent unfavorable factors with a marginal significance in multivariate analysis performed by Cox regression. Conclusion: It is suggested that high HIF-$1{\alpha}$ expression may be associated with intratumoral neovascularization possibly through HIF-VEGF pathway, and high HIF-$1{\alpha}$ expression could be associated with lymph node metastasis and post operative poor prognosis in patients with non-small cell lung carcinoma.

• Advances in Traditional Medicine
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• v.6 no.1
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• pp.12-20
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• 2006

Some natural products are able to inhibit radiation effects and exert an antitumor effect with fewer adverse reactions; however, their antitumor effects are less than those of widely-used synthetic drugs. Propolis is a natural material that has been attracting attention, and we extracted this material with water and investigated the effect of continuous propolis administration on radioactivity-induced reduction of hemocytes, in addition to the antioxidant and antitumor effects of propolis. Following a 1-week adjustment period, water-soluble propolis was administered intraperitoneally to male ICR mice at a dose of 100 mg/kg every other day for 2 weeks. Following administration, 2 Gy whole-body irradiation was performed and the counts of leukocytes, lymphocytes, and granulocytes and monocytes in the peripheral blood were determined 1, 3, 7, 15 and 30 days after irradiation. These cells were considered since they are closely associated with immunity to radioactivity. In a second experiment, water-soluble propolis was similarly administered to the mice for 2 weeks after a 1-week adjustment period, and 2 Gy whole-body irradiation was performed. The antioxidant effects in hemocytes were then investigated using 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH), a radical generator. In a third experiment, $1\;{\times}\;10^6$ Sarcoma-180 cells were inoculated into the right thigh of mice, which were divided into four groups: control, water-soluble propolis-treated, 6 Gy irradiated and water-soluble propolis-treated + 6 Gy irradiated groups, and changes in tumor size were measured for 20 days. Statistical analysis was conducted using ANOVA for multiple groups. In the three experiments, administration of water-soluble propolis inhibited the reduction of hemocytes caused by whole-body irradiation, showed antioxidant effects against radioactivity, and inhibited tumor growth, respectively. In conclusion, our data suggest that the antioxidant effect of watersoluble propolis inhibits hemocyte reduction caused by whole-body irradiation and enhances immunological inhibition of tumor growth.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.6
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• pp.2647-2650
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• 2014

Background: Colorectal cancers(CRC) are the third most common cancer in the western world, with surgery preferred for management of non-metastatic disease and post surgical treatment usually arranged according to the TNM staging system. However, there is still prognostic variation between patients who have the same stage. It is increasingly recognized that variations within disease course and clinical outcome in colorectal cancer patients are influenced by not only oncological characteristics of the tumor itself but also host response factors. Recent studies have shown correlation between the inflammatory response and clinical outcomes in various cancers. The neutrophil/lymphocyte ratio (NLR) has been described as a marker for immune response to various stimuli including cancer. Material-Methods: Two hundred eighty-one CRC patients were included in our retrospective analysis, separated into two groups according to a cut-off value for the NLR. Patient data including age, gender, vertical penetration, anatomic location, and differentiation of the tumor, TNM stage, survival rate, and disease-free survival were analyzed for correlations with the NLR. Results: Using ROC curve analysis, we determined a cut-off value of 2.2 for NLR to be best to discriminate between patient survival in the whole group. In univariate analysis, high pretreatment NLR (p=0.001, 95%CI 1.483-4.846), pathologic nodal stage (p<0.001, 95%CI 1.082-3.289) and advanced pathologic TNM stage (p<0.001, 95%CI 1.462-4.213) were predictive of shorter survival. In multivariate analysis, advanced pathologic TNM stage (p=0.001, 95%CI 1.303-26.542) and high pretreatment NLR (p=0.005, 95%CI 1.713-6.378) remained independently associated with poor survival. Conclusions: High pre-treatment NLR is a significant independent predictor of shorter survival in patients with colorectal cancer. This parameter is a simple, easily accessible laboratory value for identifying patients with poorer prognosis.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.2
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• pp.282-289
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• 2008

We evaluated the effect of SHBCS on adhesion and invasion of colon L5-26 adenocarcinoma cell line in vitro in vitro and experimental liver metastasis in vivo. SHBCS showed little inhibitory effect on colon 26-L5 cell proliferation. At the concentration of up to 500 mg/ml of SHBCS 80% of cells were viable. SHBCS showed no inhibitory effect on adhesion and invasion of colon 26-L5 cells, which were placed on matrigel. In a dose dependent manner, oral administration of SHBCS showed a significantly inhibitory effect on liver metastasis from colon 26-L5 injected mice. When mice were depleted of NK cells or macrophages before tumor inoculation, SHBCS significantly decreased liver metastasis fromf the tumor injected mice. Compared with the control mice, SHBCS increased the populations of macrophages and NK cells by 30%, 18%(10 mg/mouse, 50 mg/mouse) and 5%, 1% (10 mg/mouse, 50 mg/mouse) respectively. Compared with the control mice, SHBCS increased the populations of CD4 cells by 5%, 18% (10 mg/mouse, 50 mg/mouse) respectively. Spelenocytes from mice administerd with SHBCS were stimulated with LPS plus ConA, proliferation of splenocytes from mice administerd with SHBCS was 140%, 146%(10 mg/mouse, 50 mg/mouse) compared with th control mice. In conclusion, the present study suggests that SHBCS may have an inhibitory effect on liver metastasis through immunopotentiating activity which is associated with macrophages and NK cells.

• Korean Journal of Head & Neck Oncology
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• v.25 no.1
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• pp.18-23
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• 2009

Objectives : In $CO_2$ laser surgery for supraglottic cancer, neck dissection is generally done in second stage. We investigated simultaneous neck dissection with primary resection could be available in laser supraglottic surgery. Material and Methods : We analyzed 13 patients with supraglottic cancer who were treated with transoral supraglottic laryngectomy and simultaneous neck dissection from 2001 to 2007. Tumor stage, extent of laser surgery, histological results, survival rate, local control rate, complications, and functional results were reviewed. Results : 5-year local control rate, survival rate and disease specific survival rate from the neck was 100%, 69.9%, 100% respectively. Tracheotomy was done in all 13 cases. One patient had a long tracheotomy indwelling (191 days). In the rest of 12 patients average decanulation time was 7.4 days(1-22 days). Nasogastric tube was inserted in 5 cases, and average oral intake was possible in 3.5 days(1-16 days). Average hospital days was 29.7 days. There was no serious complication associated with neck dissection. Conclusion : Simultaneous neck dissection with primary laser resection for supraglottic cancer is oncologic sound and can be performed without significant surgical morbidity.

• Journal of Marine Bioscience and Biotechnology
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• v.1 no.2
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• pp.63-70
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• 2006

Natural product compounds are the source of numerous therapeutic agents. The marine environment produces natural products from a variety of structural classes exhibiting activity against numerous disease targets including anticancer agents. Among these, pectenotoxin-2 (PTX-2), which was first identified as a cytotoxic entity in marine sponges, which depolymerizes actin filaments, was found to be highly effective and more potent to activate an intrinsic pathway of apoptosis in p53-deficient tumor cells compared to those with functional p53 both in vitro and in vivo. However, the anti-proliferative mechanism of the compound at non-cytotoxic concentrations has not yet been explored. In the current study, we sought to investigate anti-proliferation and apoptosis of PTX-2 against U937 human leukemic cells and its underlying molecular mechanism. Exposure of U937 cells to PTX-2 resulted in growth inhibition and induction of apoptosis in dose- and time-dependent manner as measured by MTT assay, fluorescent microscopy and flow cytometric analysis. The anti-proliferative effect of PTX-2 was associated with a marked increase in the expression of cyclin-dependent kinase p21 (WAF1/CIP1) mRNA which was tumor suppressor p53-independent. The increase in apoptosis was connected with a time-dependent down-regulation of anti-apoptotic Bcl-XL and inhibitor of apoptosis proteins (IAPs) family such as XIAP and cIAP-2. Though additional studies are needed, these findings suggested that PTX-2-induced inhibition of U937 cells was associated with the induction of apoptotic cell death and the results provided important new insights into the possible molecular mechanisms of the anti-cancer activity of PTX-2.