• Radiation Oncology Journal
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• v.24 no.4
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• pp.248-254
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• 2006

$\underline{Purpose}$: To evaluate acute toxicities in cervix cancer patients receiving intensity modulated whole pelvic radiation therapy (IM-WPRT). $\underline{Materials\;and\;Methods}$: Between August 2004 and April 2006, 17 patients who underwent IM-WPRT were analysed. An intravenous contrast agent was used for radiotherapy planning computed tomography (CT). The central clinical target volume (CTV) included the primary tumor, uterus, vagina, and parametrium. The nodal CTV was defined as the lymph nodes larger than 1 cm seen on CT and the contrased-enhanced pelvic vessels. The planning target volume (PTV) was the 1-cm expanded volume around the central CTV, except for a 5-mm expansion from the posterior vagina, and the nodal PTV was defined as the nodal CTV plus a 1.5 cm margin. IM-WPRT was prescribed to deliver a dose of 50 Gy to more than 95% of the PTV. Acute toxicity was assessed with common toxicity criteria up to 60 days after radiotherapy. $\underline{Results}$: Grade 1 nausea developed in 10 (58.9%) patients, and grade 1 and 2 diarrhea developed in 11 (64.7%) and 1 (5.9%) patients, respectively. No grade 3 or higher gastrointestinal toxicity was seen. Leukopenia, anemia, and thrombocytopenia occurred in 15 (88.2%). 7 (41.2%), and 2 (11.8%) patients, respectively, as hematologic toxicities. Grade 3 leukopenia developed in 2 patients who were treated with concurrent chemoradiotherapy. $\underline{Conclusion}$: IM-WPRT can be a useful treatment for cervix cancer patients with decreased severe acute toxicities and a resultant improved compliance to whole pelvic irradiation.

• Journal of Life Science
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• v.31 no.9
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• pp.849-855
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• 2021

Recently, as nanotechnology has been introduced and used in various fields, the development of new drugs has been accelerating. Nanoparticles have maintained blood drug concentration for extended periods of time with a single administration of the drug. The drug can then be selectively released only at the pathological site, thereby reducing side effects to other non-pathological sites. In addition, nanoparticles can be modified for selective target sites delivery for other specific diseases, with polymers being widely used in the manufacture of these nanoparticles. Poly (D,L-lactic-co-glycolic acid ) (PLGA) is one of the most extensively developed biodegradable polymers. PLGA is widely used in drug delivery for a variety of applications. It has also been approved by the FDA as a drug delivery system and is widely applied in controlled release formulations, such as in gene therapy treatments. PLGA nanoparticles have been developed as delivery systems with high efficiency to specific cell types by using passive and active targeting methods. After the development of a drug delivery system using PLGA nanoparticles, the drug is selectively delivered to the target site, and the effective blood concentration for extended periods of time is optimized according to the disease. In this review paper, we focus on ways to improve cell-specific treatment outcomes by examining the development of astrocyte selective nanoparticles based on PLGA nanomaterials for gene therapy.

• Journal of Life Science
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• v.34 no.5
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• pp.287-295
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• 2024

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality worldwide, necessitating novel therapeutic strategies. The chemotherapeutic agents used to treat HCC patients are toxic and have serious side effects. Therefore, we investigated the efficacy of anticancer drugs that reduce side effects by targeting tumor cells without causing cytotoxicity in healthy hepatocytes. Berberine, an isoquinoline alkaloid derived from plant compounds, has emerged as a potential candidate for cancer treatment due to its diverse pharmacological properties. The effect of berberine on HepG2 cell viability was determined using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide assay. HepG2 cell proliferation was determined through a colony-forming assay. The effects of berberine on HepG2 cell migration were evaluated using a wound-healing assay. Berberine inhibited the proliferation of HepG2 cells, as well as colony formation and migration. Berberine treatment increased the expression of autophagy-related genes and proteins, including Beclin-1 and LC3-II, and elevated the activities and mRNA expression of Caspase-9 and Caspase-3. Additionally, in experiments utilizing the Cell-Derived Xenograft animal model, berberine treatment reduced tumor size and weight in a concentration-dependent manner. These results demonstrate the potential of berberine as a versatile anticancer agent with efficacy in both cellular and animal models of hepatocellular carcinoma. The findings herein shed light on berberine's efficacy against HCC, presenting opportunities for targeted and personalized therapeutic interventions.

• Radiation Oncology Journal
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• v.22 no.3
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• pp.165-176
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• 2004

Purpose: Firstly, to analyze facto in terms of radiation treatment that might potentially cause subfrontal relapse in two patients who had been treated by craniospinal irradiation (CSI) for medulloblastoma, Secondly, to explore an effective salvage treatment for these relapses. Materials and Methods: Two patients who had high-risk disease (T3bMl, T3bM3) were treated with combined chemoradiotherapy CT-simulation based radiation-treatment planning (RTP) was peformed. One patient who experienced relapse at 16 months after CSI was treated with salvage surgery followed by a 30.6 Gy IMRT (intensity modulated radiotherapy). The other patient whose tumor relapsed at 12 months after CSI was treated by surgery alone for the recurrence. To investigate factors that might potentially cause subfrontal relapse, we evaluated thoroughly the charts and treatment planning process including portal films, and tried to find out a method to give help for placing blocks appropriately between subfrotal-cribrifrom plate region and both eyes. To salvage subfrontal relapse in a patient, re-irradiation was planned after subtotal tumor removal. We have decided to treat this patient with IMRT because of the proximity of critical normal tissues and large burden of re-irradiation. With seven beam directions, the prescribed mean dose to PTV was 30.6 Gy (1.8 Gy fraction) and the doses to the optic nerves and eyes were limited to 25 Gy and 10 Gy, respectively. Results: Review of radiotherapy Portals clearly indicated that the subfrontal-cribriform plate region was excluded from the therapy beam by eye blocks in both cases, resulting in cold spot within the target volume, When the whole brain was rendered in 3-D after organ drawing in each slice, it was easier to judge appropriateness of the blocks in port film. IMRT planning showed excellent dose distributions (Mean doses to PTV, right and left optic nerves, right and left eyes: 31.1 Gy, 14.7 Gy, 13.9 Gy, 6.9 Gy, and 5.5 Gy, respectively. Maximum dose to PTV: 36 Gy). The patient who received IMRT is still alive with no evidence of recurrence and any neurologic complications for 1 year. Conclusion: To prevent recurrence of medulloblastoma in subfrontal-cribriform plate region, we need to pay close attention to the placement of eye blocks during the treatment. Once subfrontal recurrence has happened, IMRT may be a good choice for re-irradiation as a salvage treatment to maximize the differences of dose distributions between the normal tissues and target volume.

• Journal of Life Science
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• v.29 no.1
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• pp.105-111
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• 2019

In recent years, progress has been made in the search for the development of new anti-cancer agents by employing specific inhibitors of histone deacetylase (HDAC)-6 to block signal transduction pathways in cancer cells. This study examined the effects of tubastatin A (TubA), an HDAC-6 inhibitor, on the growth and development of immature oocytes in murine ovaries using RNA sequencing analysis. The results from a gene set enrichment analysis (GSEA) indicated that the expression of most of the gene sets involved in the cell cycle and control and progression of meiosis decreased in the TubA-treated group as compared with that in germinal vesicle (GV) stage oocytes. In addition, an ingenuity pathway analysis (IPA) suggested that TubA not only caused increased expression of p53 and pRB and decreased expression of CDK4/6 and cyclin D but also caused elevated expression of genes involved in the control of the DNA check point in G2/M stage oocytes. These results suggest that TubA may induce cell cycle arrest and apoptosis through the induction of changes in the expression of genes involved in signal transduction pathways associated with DNA damage and the cell cycle of immature oocytes in the ovary.

• Korean Journal of Clinical Laboratory Science
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• v.54 no.1
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• pp.38-48
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• 2022

Carcinoembryonic antigen (CEA) is an oncofetal antigen primarily detected in the peripheral blood of cancer patients, particularly in those with colorectal cancer. CEA is considered a valuable target for antigen-specific immunotherapy. In this study, we induced the anti-tumor immunity for CEA through the administration of a dendritic cell (DC) vaccine. However, there was a limitation in inducing tumor regression in the DC vaccinated mice. To enhance the efficacy of anti-tumor immunity in MC38/CEA2 tumor-bearing mice, we evaluated the effects of DC vaccine in combination with cyclophosphamide (CYP). Administration of CYP 100 mg/kg in mice resulted in significant inhibition of tumor growth in the 2-day tumor model, whereas a lower inhibition of tumor growth was seen in the 10-day tumor model. Therefore, the 10-day tumor model was selected for testing chemo-immunotherapy. The combined CYP and DC vaccine not only increased tumor antigen-specific immune responses but also induced synergistic anti-tumor immunity. Furthermore, the adverse effects of CYP such as weight loss and immunosuppression by regulatory T cells and myeloid-derived suppressor cells showed a significant reduction in the combined chemo-immunotherapy treatment compared with CYP alone. Our data suggest that chemoimmunotherapy with the DC vaccine may offer a new therapeutic strategy to induce a potent anti-tumor effect and reduce the adverse effects of chemotherapy.

• Journal of Life Science
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• v.29 no.4
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• pp.499-508
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• 2019

Cancer stem cells (CSCs), which are primarily responsible for metastasis and recurrence, have self-renewal, differentiation, therapeutic resistance, and tumor formation abilities. Numerous studies have demonstrated the signaling pathways essential for the acquisition and maintenance of CSC characteristics, such as WNT/${\beta}$-catenin, Hedgehog, Notch, B lymphoma Mo-MLV insertion region 1 homolog (BMI1), Bone morphogenetic protein (BMP), and TGF-${\beta}$ signals. However, few therapeutic strategies have been developed that can selectively eliminate CSCs. Recently, neutralizing antibodies against Cytotoxic T-lymphocyte associated protein 4 (CTLA-4) and Programmed cell death protein 1 (PD-1)/Programmed death-ligand 1 (PD-L1), immune checkpoint inhibitors (ICIs), have shown promising outcomes in clinical trials of melanoma, lung cancer, and pancreatic cancer, as well as in hematologic malignancies. ICIs are considered to outperform conventional anticancer drugs by maintaining long-lasting anti-cancer effects, with less severe side effects. Several studies reported that ICIs successfully blocked CSC properties in head and neck squamous carcinomas, melanomas, and breast cancer. Together, these findings suggest that novel and effective anticancer therapeutic modalities using ICIs for selective elimination of CSCs may be developed in the near future. In this review, we highlight the origin and characteristics of CSCs, together with critical signaling pathways. We also describe progress in ICI-mediated anticancer treatment to date and present perspectives on the development of CSC-targeting ICIs.

• Tuberculosis and Respiratory Diseases
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• v.62 no.1
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• pp.33-42
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• 2007

Background: Heme oxygenase-1 (HO-1) is known to modulates the cellular functions, including cell proliferation and apoptosis. It is known that a high level of HO-1 expression is found in many tumors, and HO-1 plays an important role in rapid tumor growth on account of its antioxidant and antiapoptotic effects. Cisplatin is a widely used anti-cancer agent for the treatment of lung cancer. However, the development of resistance to cisplatin is a major obstacle to its use in clinical treatment. We previously demonstrated that inhibiting HO-1 expression through the transcriptional activation of Nrf2 induces apoptosis in A549 cells. The aim of this study was to determine of the inhibiting HO-1 enhance the chemosensitivity of A549 cells to cisplatin. Materials and Methods: The human lung cancer cell line, A549, was treated cisplatin, and the cell viability was measured by a MTT assay. The change in HO-1, Nrf2, and MAPK expression after the cisplatin treatment was examined by Western blotting. HO-1 inhibition was suppressed by ZnPP, which is a specific pharmacologic inhibitor of HO activity, and small interfering RNA (siRNA). Flow cytometry analysis and Western blot were performed in to determine the level of apoptosis. The level of hydrogen peroxide ($H_2O_2$) generation was monitored fluoimetrically using 2',7'-dichlorofluorescein diacetate. Results: The A549 cells showed more resistance to the cisplatin treatment than the other cell lines examined, whereas cisplatin increased the expression of HO-1 and Nrf2, as well as the phosphorylation of MAPK in a time-dependent fashion. Inhibitors of the MAPK pathway blocked the induction of HO-1 and Nrf2 by the cisplatin treatment in A549 cells. In addition, the cisplatin-treated A549 cells transfected with dither the HO-1 small interfering RNA (siRNA) or ZnPP, specific HO-1 inhibitor, showed in a more significantly decrease in viability than the cisplatin-only-treated group. The combination treatment of ZnPP and cisplatin caused in a marked increase in the ROS generation and a decrease in the HO-1 expression. Conclusion: Cisplatin increases the expression of HO-1, probably through the MAPK-Nrf2 pathway, and the inhibition of HO-1 enhances the chemosensitivity of A549 cells to cisplatin.

• Journal of the Korea Convergence Society
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• v.10 no.1
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• pp.285-290
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• 2019

AHR regulates the expression of xenobiotics metabolizing enzymes (XMEs) as a transcription fact upon binding of ligands that are mainly aryl hydrocarbons. The role of AHR in human physiology has been intensively investigated for the past decades, however our understanding on AHR yet to be elucidated largely due to the lack of proper chemical agents. It has been demonstrated that AHR correlates to pathogenesis for some diseases in recent studies suggesting that the study on the AHR may provide a valid therapeutic target. Classical antagonists in current use are reported to be partially agonistic whereas a pure antagonist is yet to be found. In this study, phenyldiazenylaniline has been designed based on the structure of two known AHR antagonist, Resveratrol and CH223191. The derivatives of phenyldiazenylaniline have been prepared and subjected to assessment as an AHR antagonist in order to optimize the AHR antagonistic activity of the designed structure by means of convergence study of organic synthesis and molecular biology.

• Journal of Biomedical Engineering Research
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• v.37 no.1
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• pp.46-52
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• 2016

Nanoparticles have been studied as therapeutic and imaging agents for the early detection and cure of cancer, Cancer Theranostics. Nanoparticles were considered to effectively target cancer cells due to Enhanced Permeability and Retention (EPR) effect and most nanoparticles have been evaluated by using spherical shapes. However, the problem that the EPR effect is not so effective for human cancer therapy was recently brought up. Therefore, in this study, we suggest novel discoidal nanoparticles to overcome this problem, focusing on their manufacturing process and quality control. Herein, we demonstrate the improved manufacturing method of discoidal nanoparticles and their potential to apply to MCF 7, human breast cancer treatment.