• Korean Journal of Clinical Laboratory Science
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• v.37 no.3
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• pp.197-206
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• 2005

To determine the correlation between mast cells(MCs) and neoangiogenesis in the growth and progression of cervical cancer, we investigated mast cell density(MCD), microvessel density(MVD) and the expression of vascular epithelial growth factor(VEGF) in cervical intraepithelial neoplasia and invasive suqamous cell carcinoma of the uterine cervix. Forty-five cervical intraepithelial neoplasia(CIN I, II and III), 15 microinvasive carcinomas, 15 invasive squamous cell carcinomas and 20 normal cervical epithelia were included in this study. MCs were stained with anti-c-Kit antibody and alcian blue, microvessels with anti-factor VIII antibody and VEGF with anti-VEGF antibody. The adjacent fields of both normal and neoplastic epithelium were used for counting MCs and microvessels. Computerized image analysis was used to evaluate MCD and MVD. MCD and MVD were the mean numbers per $1mm^2$ counted in 5-10 high and low power fields respectively. In both c-Kit and alcian blue stained sections, MCD progressively increased along the continuum from CIN I to invasive squamous cell carcinoma(p<0.001). MVD increased significantly with cervical neoplasia progression, from CIN to invasive squamous cell carcinoma (p<0.001). In double c-Kit and Factor VIII-stained sections, MCs were mainly present in the areas adjacent to newly formed blood vessels. However, there were no significant differences in MCD and MVD between normal epithelum and CIN I. A strong correlation was also observed between MCD and MVD. In double VEGF and alcian blue-stained sections, VEGF was expressed in only MCs. Strong VEGF-positive MCs were particularly abundant around the tumorous region. Our results suggest that MCs may upregulate neoangiogenesis by VGEF secretion in the development and progression of cervical neoplasia.

• Journal of Korean Neurosurgical Society
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• v.67 no.3
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• pp.364-375
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• 2024

Objective : Kinesin family member C1 (KIFC1), a non-essential kinesin-like motor protein, has been found to serve a crucial role in supernumerary centrosome clustering and the progression of several human cancer types. However, the role of KIFC1 in glioma has been rarely reported. Thus, the present study aimed to investigate the role of KIFC1 in glioma progression. Methods : Online bioinformatics analysis was performed to determine the association between KIFC1 expression and clinical outcomes in glioma. Immunohistochemical staining was conducted to analyze the expression levels of KIFC1 in glioma and normal brain tissues. Furthermore, KIFC1 expression was knocked in the glioma cell lines, U251 and U87MG, and the functional roles of KIFC1 in cell proliferation, invasion and migration were analyzed using cell multiplication, wound healing and Transwell invasion assays, respectively. The autophagic flux and expression levels matrix metalloproteinase-2 (MMP2) were also determined using imaging flow cytometry, western blotting and a gelation zymography assay. Results : The results revealed that KIFC1 expression levels were significantly upregulated in glioma tissues compared with normal brain tissues, and the expression levels were positively associated with tumor grade. Patients with glioma with low KIFC1 expression levels had a more favorable prognosis compared with patients with high KIFC1 expression levels. In vitro, KIFC1 knockdown not only inhibited the proliferation, migration and invasion of glioma cells, but also increased the autophagic flux and downregulated the expression levels of MMP2. Conclusion : Upregulation of KIFC1 expression may promote glioma progression and KIFC1 may serve as a potential prognostic biomarker and possible therapeutic target for glioma.

• IMMUNE NETWORK
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• v.1 no.3
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• pp.260-265
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• 2001

Transforming growth $factor-{\beta}1$ ($TGF-{\beta}1$) is a multipotent growth factor affecting development, homeostasis and tissue repair. Many kinds of malignant tissues were reported to overexpress transforming growth $factor-{\beta}1$ ($TGF-{\beta}1$) gene. However, a little work has been done on the circulating $TGF-{\beta}1$ and the association of $TGF-{\beta}1$ with progression in patients with malignant tumors. In this study, we measured the plasma level of $TGF-{\beta}1$ in gastric cancer and prostate cancer patients and evaluated the utility of plasma $TGF-{\beta}1$ as a possible tumor marker. We used Enzyme-linked immunosorbent assay (ELISA) system in order to measure plasma $TGF-{\beta}1$ level in 134 gastric cancer patients, 50 prostate cancer patients and 290 normal controls. And the tumor marker, carcinoembryonic antigen (CEA), prostate-specific antigen (PSA), was compared with $TGF-{\beta}1$ in the aspects of sensitivity and specificity. The mean plasma $TGF-{\beta}1$ levels were $1.219{\pm}0.834$ (0.272-5.772) ng/mL in normal controls, $5.964{\pm}3.218$ (0.845-18.124) ng/mL in gastric cancer and $4.140{\pm}2.345$ (1.108-13.302) ng/mL in prostate cancer. In gastric cancer patients difference in plasma $TGF-{\beta}1$ level was not detected according to cancer stage. In comparison with other tumor marker (CEA, PSA) $TGF-{\beta}1$ is more potent in sensitivity. These results indicate that the plasma $TGF-{\beta}1$ level can be a potent tumor marker in gastric cancer and prostate cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.3
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• pp.909-914
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• 2012

Background: Gefitinib, a tyrosine kinase inhibitor (TKI) of epidermal growth factor receptor (EGFR), is used both as a single drug and concurrently with whole brain radiotherapy (WBRT) the standard treatment for brain metastases (BM), and is reported to be effective in a few small studies of patients with BM from non-small-cell lung cancer (NSCLC). However, no study has compared the two treatment modalities. This retrospective analysis was conducted to compare the efficacy of gefitinib alone with gefitinib plus concomitant WBRT in treatment of BM from NSCLC. Methods: We retrospectively reviewed 90 patients with BM from NSCLC who received gefitinib alone (250mg/day, gefitinib group) or with concomitant WBRT (40Gy/20f/4w, gefitinib-WBRT group) between September 2005 and September 2009 at Sun Yat-Sen University Cancer Center. Forty-five patients were in each group. Results: The objective response rate of BM was significantly higher in gefitinib-WBRT group (64.4%) compared with gefitinib group (26.7%, P<0.001). The disease control rate of BM was 71.1% in gefitinib-WBRT group and 42.2% in gefitinib group (P=0.006). The median time to progression of BM was 10.6 months in gefitinib-WBRT group and 6.57 months in gefitinib group (P<0.001). The median overall survival(OS) of gefitinib-WBRT and gefitinib alone group was 23.40 months and 14.83 months, respectively (HR, 0.432, P=0.002). Conclusion: Gefitinib plus concomitant WBRT had higher response rate of BM and significant improvement in OS compared with gefitinib alone in treatment of BM from NSCLC.

• Journal of Life Science
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• v.27 no.8
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• pp.958-964
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• 2017

Autophagy plays an important role in cellular homeostasis and survival for cell recycling and various stresses within the cell. Recent studies have shown that autophagy activity modulates the expression of oncogene and tumor suppressor genes, leading to the development or suppression of cancer. Induction of autophagy is involved in preventing cancer development in normal cells and plays an important role in prompting a specific cell death mechanism in cancer cells with damaged cell death function. It is also known that autophagy inhibition increases the therapeutic efficacy by sensitizing cancer cells that are resistant to chemotherapy. However, the role of autophagy has not yet been fully understood in cancer treatment. Oral squamous cell carcinoma accounts for more than 90% of oral cancer and is the sixth most common cancer in the world. The incidence of oral cancer has increased by 50% over the last 20 years and the mortality rate is over 40% within 5 years after the onset. In oral cancers, the role of autophagy are described to look for tumor inhibitory in the early stages of tumor formation, like other cancers, indicating the dual functions involved in tumor cell survival include tumor progression stages. This review summarizes the various roles of autophagy in cancer cells and suggests the possibility of autophagy as a promising target for effective oral cancer therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7171-7177
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• 2013

Purpose: To compare the safety and efficacy of first-line chemotherapy regimen with or without doxorubicin in treating patients with advanced soft tissue sarcoma (STS). Patients and Methods: We retrospectively analyzed a cohort of 56 patients histologically confirmed with STS who were treated at Jiangsu Cancer Hospital and Research Institute from July 2011 to June 2012.The basic element of first line chemotherapy contained epirubicin in group B and lacked epirubicin in group A. Response was assessed using RECIST criteria. The Kaplan-Meier method was used to estimate progress free survival (PFS). Results: According to RECIST criteria, patients in group treated by chemotherapy without epirubicin, the objective response (OR) ratio was 6.5 % (CR0%+PR6.5%). Disease control rate (DCR=CR+PR+SD) was 25.8% with a median follow-up of 14.6 months, including 2 patients achieving a partial response (PR 6.5%) and a stable response (SD 19.4%) in 6. In group B with epirubicin based regimens, no patient had complete response, PR (28 %) was observed in 7 and SD (24 %) in 6. DCR was observed in 13 patients (52%). By Fisher's exact test, the DCR difference between the two groups was statistically significant (p=0.046). In group A, median PFS was 3.0 months (95%CI:2.1-3.8), compared with 4.0 months (95% CI:3.03-4.97) in group B (p=0.0397 by log-rank test). Epirubicin based chemotherapy and ECOG performance status 0-1 were identified as favorable factors for progression in our cohort of patients. Differences of nonhematologic and hematologic toxicities were not statistically significant between the two groups, and the addition of epirobicin was not associated with cardiac toxicity (p=0.446). Conclusion: Our study demonstrates that epirubicin-based chemotherapy is effective and well tolerated, and is superior to chemotherapy without epirubicin regarding efficacy. Therefore it is recommended that epirubicin-based chemotherapy should be considered as first line for patients with advanced STS.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.1
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• pp.413-417
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• 2013

Purpose: This phase II study was undertaken to determine the efficacy and safety of Loubo$^{(R)}$ (Lobaplatin) in combination with pemetrexed in treating patients with metastatic breast cancer who failed to respond to anthracycline or taxanes. Patients and Methods: Metastatic breast cancer cases who had previously received an anthracycline and a taxane in either adjuvant or metastatic settings, were enrolled. All patients were recruited from Jiangsu Cancer Hospital and Research Institute, and were treated with Loubo$^{(R)}$ (Lobaplatin) 35 $mg/m^2$ (intravenous; on day 1) and pemetrexed 500 $mg/m^2$ (intravenous; on day 1) every 21 days. Efficacy and side effects were evaluated after at least two cycles of chemotherapy. Results: All eligible 19 patients completed at least 2 cycles of chemotherapy with pemetrexed and lobaplatin, and were evaluable. Overall, 3 (15.8%) patients achieved partial response, 11 (57.9%) stable disease, 5 (26.3%) progression of disease, with no complete remission. Response rate was 15.8%, disease control rate was 42.1%. The median survival time was 10.3 months. Neutrophil suppression occurred in 36.8% of patients who had grade 2 toxicity, and 26.3% had grade 3, 26.4% had grade 4. Thrombocytopenia was encountered as follows: 21.1% grade 2, 15.8% grade 3 and 5.5% grade 4. Incidences of anemia were 10.5% in grade 2, 5.3% grade 3 and 0% grade 4. Only 5.3% of patients required packed red blood cell transfusion. Grade 3 digestive tract toxicity occurred in 5.5% of patients. Other toxicities included elevated transaminase,oral mucositis and skin rashes. Conclusions: The regimen of lobaplatin and pemetrexed is modestly active in metastatic breast cancer patients who failed anthracycline or taxanes, and the toxicity profile suggesting that the doses of chemotherapy should be further modified.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3731-3740
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• 2012

Background: There have been few studies of Asian ovarian cancer and benign tumors. The primary aim of this paper was to report the protocol of the Ko-EVE study to examine epidemiological and molecular factors for ovarian cancer and benign neoplasms and to ascertain the major risk factors for ovarian cancer control in Korea. Methods: This case-control study covers incident epithelial ovarian cancers and benign neoplasms, four major centers participating in enrolling incident cases and 3 hospitals enrolling healthy controls among health examinees. Standardized questionnaires were administered by trained interviewers, including sections on socio-demographics characteristics, past medical history, medication usage, family history, lifetime consumption of alcohol and tobacco, diet, physical activity, and reproductive factors for women. Various biological specimens were collected in the biorepository according to the standardized protocol. Annual follow-up for cancer cases and follow-up at the 1st year for benign tumor cases are performing to evaluate treatment effect and progression. Passive follow to see long-term survival will be conducting using record linkage with national data. Results: The total number recruited in 2010-2011 was 246 epithelial ovarian cancer cases, 362 benign epithelial tumors and 345 controls. We are planning to collect subjects for at least 1,500 sets of ovarian cancer, 2,000 benign tumors and 1,500 controls till 2018. Conclusions: The Ko-EVE will provide unique and important data to probe the etiology and natural history of Korean epithelial ovarian cancer. It will be continued by genomic and proteomic epidemiological analyses and future intervention studies for the prevention of ovarian cancer among Koreans.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.4
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• pp.2393-2399
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• 2013

Objective: Mitochondrial DNA (mtDNA) is considered a hotspot of mutations in various tumors. However, the relationship between microsatellite instability (MSI) and mtDNA copy number alterations in lung cancer has yet to be fully clarifieds. In the current study, we investigated the copy number and MSI of mitochondrial genome in lung carcinomas, as well as their significance for cancer development. Methods: The copy number and MSI of mtDNA in 37 matched lung carcinoma/adjacent histological normal lung tissue samples were examined by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) assays for sequence variation, followed by sequence analysis and fluorogenic 5'-nuclease real-time PCR. Student's t test and linear regression analyses were employed to analyze the association between mtDNA copy number alterations and mitochondrial MSI (mtMSI). Results: The mean copy number of mtDNA in lung carcinoma tissue samples was significantly lower than that of the adjacent histologically normal lung tissue samples (p<0.001). mtMSI was detected in 32.4% (12/37) of lung carcinoma samples. The average copy number of mtDNA in lung carcinoma samples containing mtMSI was significantly lower than that in the other lung carcinoma samples (P<0.05). Conclusions: Results suggest that mtMSI may be an early and important event in the progression of lung carcinogenesis, particularly in association with variation in mtDNA copy number.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.2
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• pp.161-168
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• 2017

Understanding the crosstalk mechanisms between perivascular cells (PVCs) and cancer cells might be beneficial in preventing cancer development and metastasis. In this study, we investigated the paracrine influence of PVCs derived from human umbilical cords on the proliferation of lung adenocarcinoma epithelial cells (A549) and erythroleukemia cells (TF-$1{\alpha}$ and K562) in vitro using $Transwell^{(R)}$ co-culture systems. PVCs promoted the proliferation of A549 cells without inducing morphological changes, but had no effect on the proliferation of TF-$1{\alpha}$ and K562 cells. To identify the factors secreted from PVCs, conditioned media harvested from PVC cultures were analyzed by antibody arrays. We identified a set of cytokines, including persephin (PSPN), a neurotrophic factor, and a key regulator of oral squamous cell carcinoma progression. Supplementation with PSPN significantly increased the proliferation of A549 cells. These results suggested that PVCs produced a differential effect on the proliferation of cancer cells in a cell-type dependent manner. Further, secretome analyses of PVCs and the elucidation of the molecular mechanisms could facilitate the discovery of therapeutic target(s) for lung cancer.