• Asian Pacific Journal of Cancer Prevention
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• v.15 no.5
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• pp.2313-2318
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• 2014

Peroxisome proliferator-activated receptor gamma (PPAR-${\gamma}$), a ligand-dependent nuclear transcription factor, has been found to widely exist in tumor tissues and plays an important role in affecting tumor cell growth. In this study, we investigated the effect of PPAR-${\gamma}$ on aspects of the cervical cancer malignant phenotype, such as cell proliferation and apoptosis. Cell growth assay, Western blotting, Annexin V and flow cytometry analysis consistently showed that treatment with troglitazone (TGZ, a PPAR-${\gamma}$ agonist) led to dose-dependent inhibition of cervical cancer cell growth through apoptosis, whereas T0070907 (another PPAR-${\gamma}$ antagonist) had no effect on Hela cell proliferation and apoptosis. Furthermore, we also detected the protein expression of p53, p21 and Mdm2 to explain the underlying mechanism of PPAR-${\gamma}$ on cellular apoptosis. Our work, finally, demonstrated the existence of the TGZ-PPAR-${\gamma}$-p53 signaling pathway to be a critical regulator of cell apoptosis. These results suggested that PPAR-${\gamma}$ may be a potential therapeutic target for cervical cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5371-5374
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• 2013

Objective: Photodynamic therapy (PDT) is an emerging therapeutic procedure suitable for the treatment of cervical cancer. However, the side effects of PDT are severe, including skin ulceration, so we designed an experiment to examine the effects of multiple low-dose photodynamic therapy of 5, 10, 15, 20-tetrakis(1-methylpyridinium-4-yl) porphyrin (Tmpyp4) on tumour growth by utilizing a model in nude mice implanted with Hela cervical cancer cells. Materials and Methods: Female BALB/c nude mice (aged 5-6 weeks, weighing 18-20 g) were used. Hela cervical cancer cells were injected subcutaneously ($1{\times}10^7cells/200{\mu}L$). Ten days after injection, the mice were divided into three groups (n=6), the A group of controls without any treatment, the B group receiving a single-treatment with Tmpyp4 (10 mg/kg, intratumor injection) and irradiation (blue laser, $108J/cm^2$), and the C group given three-treatments with Tmpyp4 (10 mg/kg, intratumor injection) and irradiation at intervals of two days. After starting treatment, tumours were measured every two days, to assess growth. At 2 weeks after the last treatment of C group, tumour tissue and organs were collected from each mouse to evaluate tumor histology and organ damage. Results: Tumour growth in C group was significantly inhibited compared with A and B groups (P<0.05), without any injury to the skin and internal organs. Conclusion: Our novel findings demonstrated that multiple low-dose photodynamic therapy of Tmpyp4 could inhibit cervical cancer growth significantly with no apparent side effects.

• Radiation Oncology Journal
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• v.36 no.3
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• pp.182-191
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• 2018

Purpose: To investigate the clinical outcome of proton therapy (PT) in patients with chordoma. Materials and Methods: Fifty-eight patients with chordoma treated with PT between June 2007 and December 2015 at the National Cancer Center, Korea, were retrospectively analyzed. The median total dose was 69.6 cobalt gray equivalent (CGE; range, 64.8 to 79.2 CGE). Local progression-free survival (LPFS), distant metastasis-free survival (DMFS), overall survival (OS), and disease-specific survival (DSS) rates were calculated by the Kaplan-Meier method. Results: With the median follow-up of 42.8 months (range, 4 to 174 months), the 5-year LPFS, DMFS, OS, and DSS rates were 87.9%, 86.7%, 88.3%, and 92.9%, respectively. The tumor location was associated with the patterns of failure: the LPFS rates were lower for cervical tumors (57.1%) than for non-cervical tumors (93.1%) (p = 0.02), and the DMFS rates were lower for sacral tumors (53.5%) than for non-sacral tumors (100%) (p = 0.001). The total dose was associated with both the LPFS rate and DMFS rate. The initial tumor size was associated with the DMFS rate, but was not associated with the LPFS rate. Three patients had grade 3 late toxicity with none ≥grade 4. Conclusion: PT is an effective and safe treatment in patients with chordomas. The tumor location was associated with the patterns of failure: local failure was common in cervical tumors, and distant failure was common in sacral tumors. Further refinement of PT, such as the utilization of intensity modulated PT for cervical tumors, is warranted to improve the outcome.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.12
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• pp.4915-4918
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• 2014

Background and Aims: Advances in the treatment of cervical cancer over the last decade have predominantly involved the development of genes directed at molecular targets. Gene therapy is recognized to be a novel method for the treatment of cervical cancer. Genes can be administered into target cells via nanocarriers. This study aimed to develop systemically administrable nano-vectors. Floate (Fa) containing gene loaded nanoparticles (NPs) could target HeLa human cervical cancer cells through combination with receptors on the cells to increase the nuclear uptake of genetic materials. Methods: Fa was linked onto Poly (ethylene glycol)-b-poly (D, L-lactide) (PEG-PLA) to form Fa-PEG-PLA, and the resulting material was used to load plasmids of enhanced green fluorescence protein (pEGFP) to obtain gene loaded nanoparticles (Fa-NPs/DNA). Physical-chemical characteristics, in vitro release and cytotoxicity of Fa-NPs/DNA were evaluated. The in vitro transfection efficiency of Fa-NPs/DNA was evaluated in HeLa cells and human umbilical vein endothelial cells (HUVEC). PEG-PLA without Fa was used to load pEGFP from NPs/DNA as a control. Results: Fa-NPs/DNA has a particle size of 183 nm and a gene loading quantity of 92%. After 72h of transfection, Fa-NPs/DNA displayed over 20% higher transfection efficiency than NPs/DNA and 40% higher than naked DNA in HeLa cells. However, in HUVECs, no significant difference appeared between Fa-NPs/DNA and NPs/DNA. Conclusions: Fa-PEG-PLA NPs could function as excellent materials for gene loading. This nano-approach could be used as tumor cell targeted medicine for the treatment of cervical cancer.

• Radiation Oncology Journal
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• v.16 no.4
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• pp.357-366
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• 1998

Brachytherapy is an essential part of radiotherapy for uterine cervical cancer. The low dose rate (LDR) regimen has been the major technique of intracavitary therapy for cervical cancer. However, there has been an expansion in the last 20 years of high dose rate (HDR) machines using Ir-192 sources. Since 1979, HDR brachytherapy has been used for the treatment of uterine cervical cancer in Korea. The number of institutions employing HDR has been increasing, while the number of low dose rate system has been constant. In 1995, there was a total 27 HDR brachytherapy units installed and 1258 cases of patients with cervical cancer were treated with HDR Most common regimens of HDR brachytherapy are total dose of 30-39 Gy at point A with 10-13 fractions in three fractions per week. 24-32 Gy with 6-8 fractions in two fractions per week, and 30-35 Gy with 6-7 fractions in two fractions per week. The average fractionation regimen of HDR brachytherapy is about 8 fractions of 4.1 Gy each to Point A. In Korea, treatment results for HDR brachytherapy are comparable with the LDR series and appears to be a safe and effective alternative to LDR therapy for the treatment of cervical carcinoma. Studies from the major centers report the five-year survival rate of cervical cancer as. 78-86$\%$ for Stage 1, 68-85$\%$ for stage 11, and 38-56$\%$ for Stage III. World-wide questionnaire study and Japanese questionnaire survey of multiple institutions showed no survival difference in any stages and dose-rate effect ratio (HDR/LDR) was calculated to be 0.54 to 0.58. However the optimum treatment doses and fractionation schemes appropriate to generate clinical results comparable to conventional LDR schemes have yet to be standardized. In conclusion, HDR intracavitary radiotherapy is increasingly practiced in Korea and an effective treatment modality for cervical cancer. To determine the optimum radiotherapy dose and fractionation schedule, a nation-wide prospective study is necessary in Korea. In addition, standardization of HDR application (clinical, computer algorithms, and dosimetric aspects) is necessary.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.17 no.1
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• pp.73-81
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• 1995

The poor survival rates of patients with carcinoma of a tongue, despite of modern therapy, is well recognized. One of the most important prognostic factors is status of the cervical lymph nodes. There have been a long-standing debate about the treatment of cervical lymph nodes in early-stage tongue cancer. There are two major treatment opinion. The one is surgical excision of primary tumor with prophylactic neck dissection, simultaneously, and the other is to delay the cervical therapy until cervical lymph node is palpable. Recently we have experienced the early cervical metastasis in three patients who had been diagnosed as a carcinoma of the tongue. They were T1, T2 lesion and no palpable node was found. But histopathologic examination showed the occult metastasis or delayed cervical metastasis was occured. By the review of literature and clinical experience, we could conclude the prophylactic neck dissection offers a better chance for success than therapeutic neck dissection of palpable lymph nodes, in case of oral tongue cancer.

• Korean Journal of Pharmacognosy
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• v.53 no.1
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• pp.21-28
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• 2022

Sparassis crispa is an edible mushroom that has been widely utilized in Japan and Korea. It has various biological activities, such as anti-hypertensive, anti-allergic, anti-diabetic, anti-inflammatory, anti-angiogenic, and anti-cancer effects. In this study, we investigated the anticancer activity and underlying molecular mechanism of chloroform fraction of methanol extract of S. crispa (CESP) against cervical cancer stem cells (CSCs), which contribute to tumor initiation, recurrence, and resistance to therapy of human cervical cancer. CESP effectively inhibited the proliferation, tumorsphere formation, and migration of HeLa-derived cervical CSCs by promoting apoptosis. In addition, CESP significantly downregulated the expression of key cancer stemness markers, including integrin α6, CD133, CD44, ALDH1A1, Nanog, Oct-4, and Sox-2, in HeLa-derived cervical CSCs. Furthermore, CESP remarkably suppressed in vivo tumor growth of HeLa-derived cervical CSCs in a chick embryo chorioallantoic membrane (CAM) model. Therefore, our findings suggest that CESP has potential as a natural medicine for the prevention and treatment of cervical cancer by targeting CSCs.

• Biomolecules & Therapeutics
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• v.32 no.3
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• pp.379-389
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• 2024

This study was aimed to evaluate endogenous metabolic changes before and after cisplatin and radiation therapy in patients with cervical cancer via untargeted metabolomic analysis using plasma samples. A total of 13 cervical cancer patients were enrolled in this study. Plasma samples were collected from each patient on two occasions: approximately one week before therapy (P1) and after completion of cisplatin and radiation therapy (P2). Of the 13 patients, 12 patients received both cisplatin and radiation therapy, whereas one patient received radiation therapy alone. The samples were analyzed using the Ultimate 3000 coupled with Q Exactive^TM Focus Hybrid Quadrupole-Orbitrap^TM mass spectrometry (Thermo Fisher Scientific, Waltham, MA, USA). Chromatographic separation utilized a Kinetex C18 column 2.1×100 mm (2.6 ㎛) (Phenomenex, Torrance, CA, USA), and the temperature was maintained at 40℃. Following P2, there were statistically significant increases in the concentrations of indoxyl sulfate, phenylacetylglutamine, Lysophosphatidyethanolamine (LysoPE) (18:1), and indole-3-acetic acid compared with the concentrations observed at P1. Specifically, in the human papillomavirus (HPV) noninfection group, indoxyl sulfate, LysoPE (18:1), and phenylacetylglutamine showed statistically significant increases at P2 compared with P1. No significant changes in metabolite concentrations were observed in the HPV infection group. Indoxyl sulfate, LysoPE (18:1), phenylacetylglutamine, and indole-3-acetic acid were significantly increased following cisplatin and radiation therapy.

• Journal of Korean Traditional Oncology
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• v.21 no.1
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• pp.1-14
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• 2016

The incidence rate of cervical cancer in Korea is still higher than in other developed countries, notwithstanding the national mass screening program. Cervical cancer prognosis is good due to an effective treatment such as surgery or radiation therapy, concurrent chemotherapy in the early stage. However, it is still a poor prognosis when advanced stage or recurrent. Some studies said that combined oriental and western medicine can improve the survival, quality of life, immune function, and decrease side effects in cervical cancer. In the western medical part, clinical practice guideline was published in 2006, 2007 and 2010 in Korea. In China, oriental medicine clinical practice guideline have been published in 2014. But there is no Korean medicine clinical practice guideline. This study will introduce the methods of diagnosis and the medical therapeutics which is commonly utilized for cervical cancer in Korea, and existing Korean medicine clinical practice guideline for Disease Analysis and Treatment (辨證論治). This study will be a meaningful study to establish clinical practice guidelines of Korean Medicine for cervical cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3095-3099
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• 2016

Background: Cervical cancer is the most frequently diagnosed cancer among women in India. Understanding quality of life (QOL) in women undergoing chemo-radiotherapy for cervical cancer will help in introducing interventions for better care and outcomes in these women. This study assessed QOL before and after chemo-radiotherapy in cervical cancer patients. Materials and Methods: This follow-up study covered sixty-seven newly diagnosed women with advanced cervical cancer (stages 2b to 4b). Structured questionnaires (the European Organization for Research and Treatment of Cancer, EORTC QLQ-C30 and EORTC QLQ-CX24) were used to assess the change in QOL after 6 months of treatment. Results: The mean age of women at the time of detection of cervical cancer was $52.3{\pm}11.29$ years (Range 30-75 years). Six months survival was 92.53%. The mean global health score of cervical cancer patients after six months of treatment was 59.52, which was significantly higher than the pre-treatment score of 50.15 (p=0.00007). Physical, cognitive and emotional functioning improved significantly (p<0.05) after treatment. Fatigue, pain, insomnia and appetite loss improved but episodes of diarrhea increased after treatment. The mean "symptoms score" using EORTC QLQ-CX24 post treatment was 20.0 which was significantly lower as compared to the pre- treatment score 30.0 (p<0.00001). Sexual enjoyment and sexual functioning decreased significantly after treatment. Conclusions: QOL of newly diagnosed cervical cancer patients improved significantly following chemo-radio therapy. Enhancement was also demonstrated on three of the five functional scales of EORTC QLQ-C30. To further improve QOL, interventions focusing on social and psychological support and physical rehabilitation may be needed.