1.Anti-tumor effects of Toxoplasma gondii and antigen-pulsed dendritic cells in mice bearing breast cancer
Bong Kyun KIM ; Hei Gwon CHOI ; Jae-Hyung LEE ; In Wook CHOI ; Jae-Min YUK ; Guang-Ho CHA ; Young-Ha LEE
Parasites, Hosts and Diseases 2025;63(1):37-49
Cancer immunotherapy is widely used to treat various cancers to augment the weakened host immune response against tumors. Dendritic cells (DCs) are specialized antigen-presenting cells that play dual roles in inducing innate and adaptive immunity. Toxoplasma gondii is a protozoan parasite that exhibits anti-tumor activity against certain types of cancers. However, little is known about the anti-tumor effects of T. gondii or tumor/parasite antigen-pulsed DCs (DC vaccines, DCV) in breast cancer. In this study, C57BL/6 mice were administered E0771 mouse breast cancer cells (Cancer-injected) subcutaneously, T. gondii Me49 cysts orally (TG-injected), or DCs pulsed with breast cancer cell lysate antigen and T. gondii lysate antigens (DCV-injected) intraperitoneally. Tumor size and immunological characteristics were subsequently evaluated. We also evaluated matrix metalloproteinase (MMP)-2 and MMP-9 levels in E0771 mouse breast cancer cells co-cultured with T. gondii or DCs by RT-PCR. The tumor volumes of mice injected with breast cancer cells and antigen-pulsed DCs (Cancer/DCV-injected mice) were similar to those of Cancer-injected mice; however, they were significantly reduced in T. gondii-infected tumor-bearing (TG/Cancer-injected) mice. Moreover, tumor volumes were significantly reduced by adding antigen-pulsed DCs (TG/Cancer/DCV-injected mice) compared to TG/Cancer-injected mice. The levels of IFN-γ, serum IgG2a levels, and CD8+ T cell populations were significantly higher in DCV- and TG-injected mice than in control mice, while no significant differences between Cancer- and Cancer/DCV-injected mice were observed. The levels of IFN-γ, the IgG2a levels, and the percentage of CD8+ T cells were significantly increased in TG/Cancer- and TG/Cancer/DCV-injected mice than in Cancer-injected mice. IFN-γ levels and serum IgG2a levels were further increased in TG/Cancer/DCV-injected mice than in TG/Cancer-injected mice. The MMP-2 and MMP-9 mRNA expressions were significantly decreased in mouse breast cancer cells co-cultured with live T. gondii, T. gondii lysate antigen, or antigen-pulsed DCs (DCV) but not in inactivated DCs. These results indicate that T. gondii induces anti-tumor effects in breast cancer-bearing mice through the induction of strong Th1 immune responses, but not in antigen-pulsed DCs alone. The addition of antigen-pulsed DCs further augments the anti-tumor effects of T. gondii.
2.Anti-tumor effects of Toxoplasma gondii and antigen-pulsed dendritic cells in mice bearing breast cancer
Bong Kyun KIM ; Hei Gwon CHOI ; Jae-Hyung LEE ; In Wook CHOI ; Jae-Min YUK ; Guang-Ho CHA ; Young-Ha LEE
Parasites, Hosts and Diseases 2025;63(1):37-49
Cancer immunotherapy is widely used to treat various cancers to augment the weakened host immune response against tumors. Dendritic cells (DCs) are specialized antigen-presenting cells that play dual roles in inducing innate and adaptive immunity. Toxoplasma gondii is a protozoan parasite that exhibits anti-tumor activity against certain types of cancers. However, little is known about the anti-tumor effects of T. gondii or tumor/parasite antigen-pulsed DCs (DC vaccines, DCV) in breast cancer. In this study, C57BL/6 mice were administered E0771 mouse breast cancer cells (Cancer-injected) subcutaneously, T. gondii Me49 cysts orally (TG-injected), or DCs pulsed with breast cancer cell lysate antigen and T. gondii lysate antigens (DCV-injected) intraperitoneally. Tumor size and immunological characteristics were subsequently evaluated. We also evaluated matrix metalloproteinase (MMP)-2 and MMP-9 levels in E0771 mouse breast cancer cells co-cultured with T. gondii or DCs by RT-PCR. The tumor volumes of mice injected with breast cancer cells and antigen-pulsed DCs (Cancer/DCV-injected mice) were similar to those of Cancer-injected mice; however, they were significantly reduced in T. gondii-infected tumor-bearing (TG/Cancer-injected) mice. Moreover, tumor volumes were significantly reduced by adding antigen-pulsed DCs (TG/Cancer/DCV-injected mice) compared to TG/Cancer-injected mice. The levels of IFN-γ, serum IgG2a levels, and CD8+ T cell populations were significantly higher in DCV- and TG-injected mice than in control mice, while no significant differences between Cancer- and Cancer/DCV-injected mice were observed. The levels of IFN-γ, the IgG2a levels, and the percentage of CD8+ T cells were significantly increased in TG/Cancer- and TG/Cancer/DCV-injected mice than in Cancer-injected mice. IFN-γ levels and serum IgG2a levels were further increased in TG/Cancer/DCV-injected mice than in TG/Cancer-injected mice. The MMP-2 and MMP-9 mRNA expressions were significantly decreased in mouse breast cancer cells co-cultured with live T. gondii, T. gondii lysate antigen, or antigen-pulsed DCs (DCV) but not in inactivated DCs. These results indicate that T. gondii induces anti-tumor effects in breast cancer-bearing mice through the induction of strong Th1 immune responses, but not in antigen-pulsed DCs alone. The addition of antigen-pulsed DCs further augments the anti-tumor effects of T. gondii.
3.Anti-tumor effects of Toxoplasma gondii and antigen-pulsed dendritic cells in mice bearing breast cancer
Bong Kyun KIM ; Hei Gwon CHOI ; Jae-Hyung LEE ; In Wook CHOI ; Jae-Min YUK ; Guang-Ho CHA ; Young-Ha LEE
Parasites, Hosts and Diseases 2025;63(1):37-49
Cancer immunotherapy is widely used to treat various cancers to augment the weakened host immune response against tumors. Dendritic cells (DCs) are specialized antigen-presenting cells that play dual roles in inducing innate and adaptive immunity. Toxoplasma gondii is a protozoan parasite that exhibits anti-tumor activity against certain types of cancers. However, little is known about the anti-tumor effects of T. gondii or tumor/parasite antigen-pulsed DCs (DC vaccines, DCV) in breast cancer. In this study, C57BL/6 mice were administered E0771 mouse breast cancer cells (Cancer-injected) subcutaneously, T. gondii Me49 cysts orally (TG-injected), or DCs pulsed with breast cancer cell lysate antigen and T. gondii lysate antigens (DCV-injected) intraperitoneally. Tumor size and immunological characteristics were subsequently evaluated. We also evaluated matrix metalloproteinase (MMP)-2 and MMP-9 levels in E0771 mouse breast cancer cells co-cultured with T. gondii or DCs by RT-PCR. The tumor volumes of mice injected with breast cancer cells and antigen-pulsed DCs (Cancer/DCV-injected mice) were similar to those of Cancer-injected mice; however, they were significantly reduced in T. gondii-infected tumor-bearing (TG/Cancer-injected) mice. Moreover, tumor volumes were significantly reduced by adding antigen-pulsed DCs (TG/Cancer/DCV-injected mice) compared to TG/Cancer-injected mice. The levels of IFN-γ, serum IgG2a levels, and CD8+ T cell populations were significantly higher in DCV- and TG-injected mice than in control mice, while no significant differences between Cancer- and Cancer/DCV-injected mice were observed. The levels of IFN-γ, the IgG2a levels, and the percentage of CD8+ T cells were significantly increased in TG/Cancer- and TG/Cancer/DCV-injected mice than in Cancer-injected mice. IFN-γ levels and serum IgG2a levels were further increased in TG/Cancer/DCV-injected mice than in TG/Cancer-injected mice. The MMP-2 and MMP-9 mRNA expressions were significantly decreased in mouse breast cancer cells co-cultured with live T. gondii, T. gondii lysate antigen, or antigen-pulsed DCs (DCV) but not in inactivated DCs. These results indicate that T. gondii induces anti-tumor effects in breast cancer-bearing mice through the induction of strong Th1 immune responses, but not in antigen-pulsed DCs alone. The addition of antigen-pulsed DCs further augments the anti-tumor effects of T. gondii.
4.Anti-tumor effects of Toxoplasma gondii and antigen-pulsed dendritic cells in mice bearing breast cancer
Bong Kyun KIM ; Hei Gwon CHOI ; Jae-Hyung LEE ; In Wook CHOI ; Jae-Min YUK ; Guang-Ho CHA ; Young-Ha LEE
Parasites, Hosts and Diseases 2025;63(1):37-49
Cancer immunotherapy is widely used to treat various cancers to augment the weakened host immune response against tumors. Dendritic cells (DCs) are specialized antigen-presenting cells that play dual roles in inducing innate and adaptive immunity. Toxoplasma gondii is a protozoan parasite that exhibits anti-tumor activity against certain types of cancers. However, little is known about the anti-tumor effects of T. gondii or tumor/parasite antigen-pulsed DCs (DC vaccines, DCV) in breast cancer. In this study, C57BL/6 mice were administered E0771 mouse breast cancer cells (Cancer-injected) subcutaneously, T. gondii Me49 cysts orally (TG-injected), or DCs pulsed with breast cancer cell lysate antigen and T. gondii lysate antigens (DCV-injected) intraperitoneally. Tumor size and immunological characteristics were subsequently evaluated. We also evaluated matrix metalloproteinase (MMP)-2 and MMP-9 levels in E0771 mouse breast cancer cells co-cultured with T. gondii or DCs by RT-PCR. The tumor volumes of mice injected with breast cancer cells and antigen-pulsed DCs (Cancer/DCV-injected mice) were similar to those of Cancer-injected mice; however, they were significantly reduced in T. gondii-infected tumor-bearing (TG/Cancer-injected) mice. Moreover, tumor volumes were significantly reduced by adding antigen-pulsed DCs (TG/Cancer/DCV-injected mice) compared to TG/Cancer-injected mice. The levels of IFN-γ, serum IgG2a levels, and CD8+ T cell populations were significantly higher in DCV- and TG-injected mice than in control mice, while no significant differences between Cancer- and Cancer/DCV-injected mice were observed. The levels of IFN-γ, the IgG2a levels, and the percentage of CD8+ T cells were significantly increased in TG/Cancer- and TG/Cancer/DCV-injected mice than in Cancer-injected mice. IFN-γ levels and serum IgG2a levels were further increased in TG/Cancer/DCV-injected mice than in TG/Cancer-injected mice. The MMP-2 and MMP-9 mRNA expressions were significantly decreased in mouse breast cancer cells co-cultured with live T. gondii, T. gondii lysate antigen, or antigen-pulsed DCs (DCV) but not in inactivated DCs. These results indicate that T. gondii induces anti-tumor effects in breast cancer-bearing mice through the induction of strong Th1 immune responses, but not in antigen-pulsed DCs alone. The addition of antigen-pulsed DCs further augments the anti-tumor effects of T. gondii.
5.Anti-tumor effects of Toxoplasma gondii and antigen-pulsed dendritic cells in mice bearing breast cancer
Bong Kyun KIM ; Hei Gwon CHOI ; Jae-Hyung LEE ; In Wook CHOI ; Jae-Min YUK ; Guang-Ho CHA ; Young-Ha LEE
Parasites, Hosts and Diseases 2025;63(1):37-49
Cancer immunotherapy is widely used to treat various cancers to augment the weakened host immune response against tumors. Dendritic cells (DCs) are specialized antigen-presenting cells that play dual roles in inducing innate and adaptive immunity. Toxoplasma gondii is a protozoan parasite that exhibits anti-tumor activity against certain types of cancers. However, little is known about the anti-tumor effects of T. gondii or tumor/parasite antigen-pulsed DCs (DC vaccines, DCV) in breast cancer. In this study, C57BL/6 mice were administered E0771 mouse breast cancer cells (Cancer-injected) subcutaneously, T. gondii Me49 cysts orally (TG-injected), or DCs pulsed with breast cancer cell lysate antigen and T. gondii lysate antigens (DCV-injected) intraperitoneally. Tumor size and immunological characteristics were subsequently evaluated. We also evaluated matrix metalloproteinase (MMP)-2 and MMP-9 levels in E0771 mouse breast cancer cells co-cultured with T. gondii or DCs by RT-PCR. The tumor volumes of mice injected with breast cancer cells and antigen-pulsed DCs (Cancer/DCV-injected mice) were similar to those of Cancer-injected mice; however, they were significantly reduced in T. gondii-infected tumor-bearing (TG/Cancer-injected) mice. Moreover, tumor volumes were significantly reduced by adding antigen-pulsed DCs (TG/Cancer/DCV-injected mice) compared to TG/Cancer-injected mice. The levels of IFN-γ, serum IgG2a levels, and CD8+ T cell populations were significantly higher in DCV- and TG-injected mice than in control mice, while no significant differences between Cancer- and Cancer/DCV-injected mice were observed. The levels of IFN-γ, the IgG2a levels, and the percentage of CD8+ T cells were significantly increased in TG/Cancer- and TG/Cancer/DCV-injected mice than in Cancer-injected mice. IFN-γ levels and serum IgG2a levels were further increased in TG/Cancer/DCV-injected mice than in TG/Cancer-injected mice. The MMP-2 and MMP-9 mRNA expressions were significantly decreased in mouse breast cancer cells co-cultured with live T. gondii, T. gondii lysate antigen, or antigen-pulsed DCs (DCV) but not in inactivated DCs. These results indicate that T. gondii induces anti-tumor effects in breast cancer-bearing mice through the induction of strong Th1 immune responses, but not in antigen-pulsed DCs alone. The addition of antigen-pulsed DCs further augments the anti-tumor effects of T. gondii.
6.The Treatment of Metastatic and Castration-Resistant Prostate Cancer Patients in Korea
Yoon Soo HAH ; U Syn HA ; Jin Woo JUNG ; Bong Hee PARK ; Hyung Joon KIM ; Ki Hong KIM ; Jeong Kyun YEO
Korean Journal of Urological Oncology 2019;17(1):48-59
The treatment of advanced prostate cancer has rapidly evolved. Androgen deprivation therapy is recognized as the first-line therapy for metastatic disease; however, a substantial proportion of patients will eventually progress to develop castration-resistance. For the past several years, docetaxel-based chemotherapy has shown significant therapeutic benefit in castration-resistant prostate cancer. Over the last 5 years, several new agents such as the enzalutamide, abiraterone, cabazitaxel, and 223radium have been developed which have all been associated with improved quality of life, pain palliation, and an increase in survival. Unfortunately, there are no Korean treatment guideline for metastatic prostate cancer and/or castration-resistant prostate cancer which has been developed based on adequate review and assessment of evidences. Thus, a guideline adequate for domestic circumstances is eagerly needed. The Korean Association for Clinical Oncology, the Korean Prostate Society, the Korean Urological Oncology Society, and the Korean Society of Pathologists reviewed and endorsed the guidelines.
Drug Therapy
;
Humans
;
Korea
;
Medical Oncology
;
Prostate
;
Prostatic Neoplasms
;
Quality of Life
7.Negative pathology after endoscopic resection of gastric epithelial neoplasms: importance of pit dysplasia.
Joon Hyung JHI ; Gwang Ha KIM ; Ahrong KIM ; Young Geum KIM ; Cheong Su HWANG ; Sojeong LEE ; Bong Eun LEE ; Geun Am SONG ; Do Youn PARK
The Korean Journal of Internal Medicine 2017;32(4):647-655
BACKGROUND/AIMS: Endoscopic resection (ER) is a well-established treatment modality for gastric epithelial neoplasm. However, there is a discrepancy between forceps biopsy and ER specimen pathology, including a negative pathologic diagnosis (NPD) after ER. It has been suggested that pit dysplasia (PD) is a subtype of gastric dysplasia, and the aim of this study was to assess the significance of PD in cases with NPD after ER for early gastric neoplasms. METHODS: After ER, 29 NPD lesions that had an associated pretreatment forceps biopsy specimen, were correctly targeted during ER, and had no cautery artifact on the resected specimen were included in this study. RESULTS: Sixteen lesions showed PD and 13 had no neoplastic pathology. The initial pretreatment forceps biopsy diagnoses of 29 NPD lesions were low-grade dysplasia (LGD) in 17 lesions, high-grade dysplasia (HGD) in seven lesions, and adenocarcinoma in five lesions, which after review were revised to PD in 19 lesions, LGD in four lesions, adenocarcinoma in two lesions, and no neoplastic pathology in four lesions. Overall, nine lesions (31%) were small enough to be removed by forceps biopsy, four NPD lesions (14%) were initially misinterpreted as neoplastic lesions, and 16 PD lesions (55%) were misinterpreted as NPD lesions on ER slides. CONCLUSIONS: Approximately half of the lesions initially diagnosed as LGD or HGD were subsequently classified as PD. Therefore, including PD as a subtype of gastric dysplasia could reduce the diagnostic discrepancy between initial forceps biopsy and ER specimens.
Adenocarcinoma
;
Artifacts
;
Biopsy
;
Cautery
;
Diagnosis
;
Neoplasms, Glandular and Epithelial*
;
Pathology*
;
Stomach
;
Stomach Neoplasms
;
Surgical Instruments
8.The Role of Spinal Dopaminergic Transmission in the Analgesic Effect of Nefopam on Rat Inflammatory Pain.
Do Yun KIM ; Joo Wung CHAE ; Chang Hun LIM ; Bong Ha HEO ; Keun Suk PARK ; Hyung Gon LEE ; Jeong Il CHOI ; Myung Ha YOON ; Woong Mo KIM
The Korean Journal of Pain 2016;29(3):164-171
BACKGROUND: Nefopam has been known as an inhibitor of the reuptake of monoamines, and the noradrenergic and/or serotonergic system has been focused on as a mechanism of its analgesic action. Here we investigated the role of the spinal dopaminergic neurotransmission in the antinociceptive effect of nefopam administered intravenously or intrathecally. METHODS: The effects of intravenously and intrathecally administered nefopam were examined using the rat formalin test. Then we performed a microdialysis study to confirm the change of extracellular dopamine concentration in the spinal dorsal horn by nefopam. To determine whether the changes of dopamine level are associated with the nefopam analgesia, its mechanism was investigated pharmacologically via pretreatment with sulpiride, a dopaminergic D2 receptor antagonist. RESULTS: When nefopam was administered intravenously the flinching responses in phase I of the formalin test were decreased, but not those in phase II of the formalin test were decreased. Intrathecally injected nefopam reduced the flinching responses in both phases of the formalin test in a dose dependent manner. Microdialysis study revealed a significant increase of the level of dopamine in the spinal cord by intrathecally administered nefopam (about 3.8 fold the baseline value) but not by that administered intravenously. The analgesic effects of intrathecally injected nefopam were not affected by pretreatment with sulpiride, and neither were those of the intravenous nefopam. CONCLUSIONS: Both the intravenously and intrathecally administered nefopam effectively relieved inflammatory pain in rats. Nefopam may act as an inhibitor of dopamine reuptake when delivered into the spinal cord. However, the analgesic mechanism of nefopam may not involve the dopaminergic transmission at the spinal level.
Analgesia
;
Animals
;
Dopamine
;
Microdialysis
;
Nefopam*
;
Pain Measurement
;
Rats*
;
Spinal Cord
;
Spinal Cord Dorsal Horn
;
Sulpiride
;
Synaptic Transmission
9.Advantage of Minimal Anterior Knee Pain and Long-term Survivorship of Cemented Single Radius Posterior-Stabilized Total Knee Arthroplasty without Patella Resurfacing.
Hyung Min JI ; Yong Chan HA ; Ji Hoon BAEK ; Young Bong KO
Clinics in Orthopedic Surgery 2015;7(1):54-61
BACKGROUND: The single radius total knee prosthesis was introduced with the advantage of reduced patellar symptoms; however, there is no long-term follow-up study of the same. The purpose of this study was to determine the survival rate of single radius posterior-stabilized total knee arthroplasty and patellofemoral complication rates in a consecutive series. METHODS: Seventy-one patients (103 knees) who underwent arthroplasty without patellar resurfacing using a single radius posterior-stabilized total knee prosthesis were followed up for a minimum 10 years. Clinical evaluation using Knee Society knee and function scores and radiologic evaluation were performed at regular intervals. Anterior knee pain as well as patellofemoral complications were evaluated with a simple questionnaire. The Kaplan-Meier product-limit method was used to estimate survival. RESULTS: Seventeen patients (23 knees) were excluded due to death (12 knees) or lost to follow-up (11 knees). Of the 80 knees enrolled, all femoral components and 78 tibial components were well fixed without loosening at final follow-up. Two revisions were performed because of tibial component loosening and periprosthetic joint infection. One patient with tibial component loosening refused to have revision surgery. No obvious tibial insert polyethylene wear was observed. The survivorships at 132 months were 96.7% using revision or pending revision as end points. Anterior knee pain was present in 6 patients (6 knees, 7.5%) at the latest follow-up. No patellofemoral complication requiring revision was encountered. CONCLUSIONS: The single radius posterior-stabilized total knee prosthesis demonstrated an excellent minimum 10-year survivorship. The low rates of implant loosening and 7.5% of anterior knee pain as a patellofemoral complication are comparable with those reported for other modern total knee prosthesis.
Aged
;
Arthralgia/*surgery
;
Arthroplasty, Replacement, Knee/*instrumentation/*methods
;
Cementation
;
Female
;
Follow-Up Studies
;
Humans
;
Knee Joint/*surgery
;
Knee Prosthesis
;
Male
;
Middle Aged
;
Patella/surgery
;
Prosthesis Failure
;
Retrospective Studies
;
Treatment Outcome
10.Predictors for Presence and Severity of Obstructive Sleep Apnea in Snoring Patients: Significance of Neck Circumference.
Si Eun KIM ; Bong Soo PARK ; Si Hyung PARK ; Kyong Jin SHIN ; Sam Yeol HA ; JinSe PARK ; Kang Min PARK
Journal of Sleep Medicine 2015;12(2):34-38
OBJECTIVES: Documented risk factors for obstructive sleep apnea include advanced age, male gender, hypertension, large neck circumference, and obesity; but some controversy remains regarding the risk factors, especially in Asians. In this study, we evaluated the risk factors for obstructive sleep apnea in snoring patients, and also analyzed the risk factors that could predict the severity of obstructive sleep apnea. METHODS: The inclusion criteria were patients 1) who visited our hospital with a chief complaint of snoring as witnessed by a sleep partner and 2) who underwent overnight polysomnography. The primary endpoint was the presence of obstructive sleep apnea as a dependent variable. RESULTS: One hundred forty-seven patients met the inclusion criteria. Of the 147 patients, 109 patients were diagnosed with obstructive sleep apnea. Multivariate analysis showed that old age and large neck circumference were significant independent variables for predicting the presence of obstructive sleep apnea, whereas hypertension and large neck circumference were independent variables for predicting the severity of obstructive sleep apnea. CONCLUSIONS: We demonstrated that neck circumference can be used to predict the presence as well as the severity of obstructive sleep apnea in snoring Asian patients.
Asian Continental Ancestry Group
;
Humans
;
Hypertension
;
Male
;
Multivariate Analysis
;
Neck*
;
Obesity
;
Polysomnography
;
Risk Factors
;
Sleep Apnea Syndromes
;
Sleep Apnea, Obstructive*
;
Snoring*

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