• Korean Journal of Head & Neck Oncology
• /
• v.22 no.2
• /
• pp.123-129
• /
• 2006

Objective ： This retrospective study was designed to evaluate the anti-tumor efficacy and toxicities of the radiation therapy(RT) combined with cisplatin-based chemotherapy in locally advanced nasopharyngeal cancer(NPC). Materials and Methods ： Fifty three patients with locally advanced NPCs(AJCC stage II, III, IV) received curative RT and cisplatin-based chemotherapy. Duration of follow-up ranged from 5.5 to 201 months(median 50.8 months). Nineteen patients(35.8%) were treated with induction chemotherapy including cisplatin $100mg/m^2$ for 1 day and 5-fluorouracil $1g/m^2$ for 5 days followed by RT(Induction CTx-RT). Another 34 patients (64.2%) were treated with concurrent chemoradiation(CCRT) using cisplatin $100mg/m^2$(D1, 22, 43). Results ： Thirty-six(67.9%) and 11(20.8%) patients achieved clinical complete response and partial response, respectively. The pattern of failure was as follows：14 locoregional recurrence(26.4%) and 7 distant metastasis(13.2%). Among them, two patients(3.8%) had both locoregional and distant failure. Median overall survival(OS) and progression-free survival(PFS) were 85.5 months and 87.5 months, respectively. Five-year OS rate was 57.1%. The stage(AJCC), tumor response to chemoradiation and T stage were significant prognostic factors for OS(p=0.0113, p=0.0362 and p=0.0469). The stage(AJCC), tumor response to chemoradiation were also significant prognostic factors for PFS(p=0.0329, p=0.0424). Compared to each treatment group(Induction CTx-RT vs. CCRT), there were no significant differences in OS and PFS(p=0.7000, p=0.8261). Grade 3-4 mucositis, nausea/vomiting and hematological toxicities were noticed in 35.8%, 11.3% and 13.2%, respectively. Delayed RT over 2 weeks was inevitable in 26.5%. Seventeen patients(50%) successfully completed planned 3 courses of cisplatin in CCRT group. Conclusions ： RT combined with cisplatin-based chemotherapy in locally advanced NPC showed high response rate, good locoregional control, and survival rate. As expected, frequency of acute toxicities increased, and the patient's compliance to treatment was need to be improved. Although our data could not show additional survival benefit of CCRT compare to that of induction chemotherapy followed by RT, patients' accrual and further follow-up are required due to limitation of retrospective study.

• Journal of Life Science
• /
• v.27 no.1
• /
• pp.1-7
• /
• 2017

Abnormal actin remodeling is a typical characteristic of tumor cells. Thymosin ${\beta}_{10}$ (TB10) and profilin-1 (PFN-1) are actin-binding proteins and essential regulators of actin polymerization. We previously showed that TB10 induced death in ovarian cancer cells by sequestering F-actin, but the underlying mechanisms of this induction have not been explored. In this study, we identified TB10 as a novel regulator of PFN-1 and demonstrated its novel function as a tumor suppressor in ovarian cancer cell lines. The present study investigated protein expression profiles through polyacrylamide gel electrophoresis (PAGE) and liquid chromatography-mass spectroscopy (LC-MS/MS) in SKOV3 cells, an ovarian cancer cell line, that were transiently transfected with TB10. PFN-1 was highly overexpressed in response to TB10, and overexpression of PFN-1 resulted in inhibition of cell proliferation and migration and promotion of cellular apoptosis in ovarian cancer cells. Furthermore, transiently transfected PFN-1 appeared to deactivate the Erk signaling pathway, followed by decreased expression of Elk-1 and Egr-1 in human ovarian cancer cells. Interestingly, PFN-1 did not affect the activation of Akt. The results demonstrated that PFN-1 induced apoptotic cell death and inhibited proliferation and migration in ovarian cancer cells, suggesting that PFN-1 may be valuable in anti-cancer therapy.

• Journal of the korean academy of Pediatric Dentistry
• /
• v.36 no.4
• /
• pp.607-612
• /
• 2009

The malignant tumor in childhood is one of the main causes of children s death due to disease. The traditional treatment for the malignancy is known for the radiation therapy and the chemical therapy or both. However, the treatments tend to induce intraoral complications. Different from adults, almost all children on cancer therapy are expected to have dental complications, because their permanent teeth are on the developmental stage. The degree of dental complication depends on the patient's age, type of chemical and other factors-radiation dose and frequency. In this report, 3 children who had experienced the anti-cancer therapy on their age between 1 and 4 years were selected and dental complications were examined. The children have chance for the various oral complications including the developmental problems such as agenesis, microdontia and hypoplasia of the teeth. Therefore, it's important to understand the side-effects of anticancer therapy during the permanent teeth had been developmental stage in young patients. Also, oral health care specialists, including pediatric and hospital dentist can support the oncology team by providing basic oral care, implementing oral care protocols, delivering emergency dental treatment undergoing anticancer treatment.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• v.26 no.1
• /
• pp.18-23
• /
• 2000

The changes of the microorganism composition after therapeutic radiation for oral cancer patients are not well known and the long-term follow-up data are not reported. To obtain basic data for understanding of pathogenesis and prevention and treatment of dental caries and mucositis occuring after radiation therapy, 7 of the oral cancer patients presented at the Seoul National University Oral & Maxillofacial Department between 1997 and 1998 whose treatment plan included radiation therapy were recruited to investigate the changes in bacterial composition(total aerobic count, Candida, Staphylococci, Lactobacilli, S. mutans, and S. salivarius (mitis, sanguis)) of the saliva before, during, and after radiation therapy. The basic data obtained from this study on identification and composition change of the bacteria in saliva of patients treated with radiation therapy can be used (1) as a reference for deciding on the ideal anti-microbial spectrum of the oral rinsing agent to be used in patients treated with radiation therapy for malignant tumor of the head and neck region. (2) to enhance the understanding of increase of opportunistic infection after immunochemical changes of the saliva and its relation to specific bacterial infection. (3) as a reference in prescribing prophylactic antibiotics in immunodepressed patients after radiation therapy.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.18
• /
• pp.8533-8539
• /
• 2016

Background: B-cell chronic lymphocytic leukemia B (B-CLL), the most common type of leukemia, may be caused by apoptosis deficiency in the body. Adipose tissue-derived mesenchymal stem cells (AD-MSCs) as providers of pro-apoptotic molecules such as tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), can be considered as an effective anti-cancer therapy candidate. Therefore, in this study we assessed the role of tumor necrosis factor-producing mesenchymal stem cells oin apoptosis of B-CLL cells resistant to fludarabine-based chemotherapy. Materials and Methods: In this study, after isolation and culture of AD-MSCs, a lentiviral LeGO-iG2-TRAIL-GFP vector containing a gene producing the ligand pro-apoptotic with plasmid PsPAX2 and PMDG2 virus were transfected into cell-lines to generate T293HEK. Then, T293HEK cell supernatant containing the virus produced after 48 and 72 hours was collected, and these viruses were transduced to reprogram AD-MSCs. Apoptosis rates were separately studied in four groups: group 1, AD-MSCs-TRAIL; group 2, AD-MSCs-GFP; group 3, AD-MSCs; and group 4, CLL. Results: Observed apoptosis rates were: group 1, $42{\pm}1.04%$; group 2, $21{\pm}0.57%$; group 3, $19{\pm}2.6%$; and group 4, % $0.01{\pm}0.01$. The highest rate of apoptosis thus occurred ingroup 1 (transduced TRAIL encoding vector). In this group, the average medium-soluble TRAIL was 72.7pg/m and flow cytometry analysis showed a pro-apoptosis rate of $63{\pm}1.6%$, which was again higher than in other groups. Conclusions: In this study we have shown that tumor necrosis factor (TNF) secreted by AD-MSCs may play an effective role in inducing B-CLL cell apoptosis.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.3
• /
• pp.1241-1245
• /
• 2015

Background: Thyroid carcinoma is the most common malignancy of the endocrine organs. Although the majority of thyroid cancer patients experience positive outcomes, anaplastic thyroid carcinoma is considered one of the most aggressive malignancies. Current therapeutic regimens do not confer a significant survival benefit, and new therapies are urgently needed. Oncolytic herpes simplex virus (oHSV) may represent a promising therapy for cancer. In the present study, we investigated the therapeutic effects of a third-generation HSV vector, $G47{\Delta}$, on various human thyroid carcinoma cell lines in vitro. Two subcutaneous (s.c.) models of anaplastic thyroid carcinoma were also established to evaluate the in vivo anti-tumor efficacy of $G47{\Delta}$. Materials and Methods: The human thyroid carcinoma cell line ARO, FRO, WRO, and KAT-5, were infected with $G47{\Delta}$ at different multiplicities of infection (MOIs) in vitro. The survival rates of infected cells were calculated each day. Two s.c. tumor models were established using ARO and FRO cells in Balb/c nude mice, which were intratumorally (i.t.) treated with either $G47{\Delta}$ or mock. Tumor volumes and mouse survival times were documented. Results: $G47{\Delta}$ was highly cytotoxic to different types of thyroid carcinomas. For ARO, FRO, and KAT-5, greater than 30% and 80% of cells were killed at MOI=0.01 and MOI=0.1, respectively on day 5. WRO cells displayed modest sensitivity to $G47{\Delta}$, with only 21% and 38% of cells killed. In the s.c. tumor model, both of the anaplastic thyroid carcinoma cell lines (ARO and FRO) were highly sensitive to $G47{\Delta}$; $G47{\Delta}$ significantly inhibited tumor growth and prolonged the survival of mice bearing s.c. ARO and FRO tumors. Conclusions: The oHSV $G47{\Delta}$ can effectively kill different types of human thyroid carcinomas in vitro. $G47{\Delta}$ significantly inhibited growth of anaplastic thyroid carcinoma in vivo and prolonged animal survival. Therefore, $G47{\Delta}$ may hold great promise for thyroid cancer patients.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.16
• /
• pp.6813-6823
• /
• 2015

Glioblastoma, also known as glioblastoma multiforme (GBM), is the most aggressive of human brain tumors and has a stunning progression with a mean survival of one year from the date of diagnosis. High cell proliferation, angiogenesis and/or necrosis are histopathological features of this cancer, which has no efficient curative therapy. This aggressiveness is associated with particular heterogeneity of the tumor featuring multiple genetic and epigenetic alterations, but also with implications of aberrant signaling driven by growth factors. The transforming growth factor ${\beta}$ ($TGF{\beta}$) superfamily is a large group of structurally related proteins including $TGF{\beta}$ subfamily members Nodal, Activin, Lefty, bone morphogenetic proteins (BMPs) and growth and differentiation factor (GDF). It is involved in important biological functions including morphogenesis, embryonic development, adult stem cell differentiation, immune regulation, wound healing and inflammation. This superfamily is also considered to impact on cancer biology including that of GBM, with various effects depending on the member. The $TGF{\beta}$ subfamily, in particular, is overexpressed in some GBM types which exhibit aggressive phenotypes. This subfamily impairs anti-cancer immune responses in several ways, including immune cells inhibition and major histocompatibility (MHC) class I and II abolishment. It promotes GBM angiogenesis by inducing angiogenic factors such as vascular endothelial growth factor (VEGF), plasminogen activator inhibitor (PAI-I) and insulinlike growth factor-binding protein 7 (IGFBP7), contributes to GBM progression by inducing metalloproteinases (MMPs), "pro-neoplastic" integrins (${\alpha}v{\beta}3$, ${\alpha}5{\beta}1$) and GBM initiating cells (GICs) as well as inducing a GBM mesenchymal phenotype. Equally, Nodal promotes GICs, induces cancer metabolic switch and supports GBM cell proliferation, but is negatively regulated by Lefty. Activin promotes GBM cell proliferation while GDF yields immune-escape function. On the other hand, BMPs target GICS and induce differentiation and sensitivity to chemotherapy. This multifaceted involvement of this superfamily in GBM necessitates different strategies in anti-cancer therapy. While suppressing the $TGF{\beta}$ subfamily yields advantageous results, enhancing BMPs production is also beneficial.

• Journal of radiological science and technology
• /
• v.29 no.4
• /
• pp.285-291
• /
• 2006

During cancer therapy, gamma-ray irradiation and treatment of anti-cancer chemicals destroy the normal cells as well as cancer cells. In this study, we investigated the effect of epigallocathechin-gallate(EGCG) extracted from green tea, which is known to have anti-cancer and anti-oxident activities, in order to find out the feasible method to protect the normal cells and to kill the cancer cells efficiently. We investigated the effect of EGCG on the leukemia cell growth and cell necrosis, especially when treated along with gamma radiation. The EGCG inhibited the leukemia cell, HL-60, growth at the appropriate concentration while it exhibited no influence on the normal cell growth. More significantly, it enhanced leukemia cell necrosis when its treatment was combined with gamma irradiation. Simultaneous treatment of EGCG and gamma radiation increased leukemia cell necrosis up to 35% compared with separate treatments. These results suggest that drinking of green tea or co-treatment of EGCG during gamma irradiation therapy may result in better prognosis through enhancement of the tumor cell necrosis and protection of the normal cells.

• Biomolecules & Therapeutics
• /
• v.30 no.6
• /
• pp.553-561
• /
• 2022

Chronic myeloid leukemia (CML) is a slowly progressing hematopoietic cell disorder. Sphingosine kinase 1 (SPHK1) plays established roles in tumor initiation, progression, and chemotherapy resistance in a wide range of cancers, including leukemia. However, small-molecule inhibitors targeting SPHK1 in CML still need to be developed. This study revealed the role of SPHK1 in CML and investigated the potential anti-leukemic activity of hirsuteine (HST), an indole alkaloid obtained from the oriental plant Uncaria rhynchophylla, in CML cells. These results suggest that SPHK1 is highly expressed in CML cells and that overexpression of SPHK1 represents poor clinical outcomes in CML patients. HST exposure led to G2/M phase arrest, cellular apoptosis, and downregulation of Cyclin B1 and CDC2 and cleavage of Caspase 3 and PARP in CML cells. HST shifted sphingolipid rheostat from sphingosine 1-phosphate (S1P) towards the ceramide coupled with a marked inhibition of SPHK1. Mechanistically, HST significantly blocked SPHK1/S1P/S1PR1 and BCR-ABL/PI3K/Akt pathways. In addition, HST can be docked with residues of SPHK1 and shifts the SPHK1 melting curve, indicating the potential protein-ligand interactions between SPHK1 and HST in both CML cells. SPHK1 overexpression impaired apoptosis and proliferation of CML cells induced by HST alone. These results suggest that HST, which may serve as a novel and specific SPHK1 inhibitor, exerts anti-leukemic activity by inhibiting the SPHK1/S1P/S1PR1 and BCR-ABL/PI3K/Akt pathways in CML cells, thus conferring HST as a promising anti-leukemic drug for CML therapy in the future.

• Journal of Chest Surgery
• /
• v.25 no.9
• /
• pp.948-954
• /
• 1992

In spite of recent progress in anticancer chemotherapy, the survival of patients with metastases to the lung treated nonsurgically has been extremely poor. So we adopted more aggressive surgical approaches for the treatment of patients with pulmonary metastases since 1985. We experienced 22 operations of metastatic lung cancer in 19 patients in the department of Thoracic & Cardiovascular Surgery in Kosin Medical College since 1985, so we reviewed the results of treatment retrospectively. The results were as follows: 1. The primary organs of metastatic lung cancer were 4 cases in each of the breast, uterus, and extremities, 3 cases in the rectum, 2 cases in the kidney, 1 case in each of the pelvis and liver, and the pathological findings were 13 cases in carcinoma and 6 cases in sarcoma. 2. The treatments for primary lesions were 15 cases of the operations with anticancer chemotherapy or radiation therapy, 2 cases of choriocarcinoma with anticancer chemotherapy only, 1 cases of uterine cervical carcinoma with chemo-radiation therapy, and 1 case of pelvic synovia sarcoma with intra-arterial anticancer chemotherapy. 3. Disease free intrerval were as follows: 7 cases were in 2 years to 4 years, 4 cases were in 1 year to 2 years, and 5 cases were beyond one year, of them one case was discovered primary lesion and metastatic lung tumor concomittently. 3 cases were above 4 years, of them one case of breast cancer were above 13 years especially. 4. The sites of metastatic lung cancer was 15 lesions in the right lung, and 9 lesions in the left lung, And the lobar sites were 10 lesions in the upper lobe, 2 lesions in the middle lobe, and 12 lesions in the lower lobe. 5. The operative methods of metastatic lung cancer were 7 case of partial resection of lung, 12 cases of pulmonary lobectomy, 1 case of pneumonectomy and 1 case of dissection of mediastinal lymph node. 6. The postoperative complications were 1 case of mild respiratory insufficency, 1 cases of pyothorax, and 1 case of urethral stricture. 7. Postoperative adjuvant therapy were as follows: No adjuvant therapy were 4 cases, anti-cancer chemotherapy were 8 cases, radiation therapy was 1 case, and combined with chemo k radiation therapy were 8 cases. 8. The results of long term follow-up were as follows: The 5 patients were died at 2 months, 22 months, 24 months, 32 months, and 49 months postoperatively, so mean survival period was 32 months postoperatively excluding one patient who was died at 2 months postoperatively. And 14 patients are aliving, of them 3 patients are living in recurred state, and the other 11 patients are living without any evidence of recurrence.