Background: Immunization of dendritic cells (DCs) pulsed with tumor antigen can activate tumor-specific cytotoxic T lymphocytes (CTL) that are responsible for protection and regression. In this study, we examined whether the uptake of necrotic tumor cells could modulate DC phenotypes and whether the immunization of necrotic tumor cell-loaded DCs could elicit efficient tumor specific immune responses followed by a regression of established tumor burdens. Methods: We prepared necrotic tumor cell-pulsed DCs for the therapeutic vaccination and investigated their phenotypic characteristics, the immune responses induced by these DCs, and therapeutic vaccine efficacy against colon carcinoma in vivo. Several parameters including phagocytosis of tumor cells, surface antigen expression, chemokine receptor expression, IL-12 production, and NK as well as CTL activation were assessed to characterize the immune response. Results: DCs derived from mouse bone marrow efficiently phagocytosed necrotic tumor cells and after the uptake, they produced remarkably increased levels of IL-12. A decreased CCR1 and increased CCR7 expression on DCs was also observed after the tumor uptake, suggesting that antigen uptake could induce DC maturation. Furthermore, co-culturing of DCs with NK cells in vitro enhanced IL-12 production in DCs and IFN-${\gamma}$ production in NK cells, which was significantly dependent on IL-12 production and cell-to-cell contact. Immunization of necrotic tumor cell-loaded DCs induced cytotoxic T lymphocytes as well as NK activation, and protected mice against subsequent tumor challenge. In addition, intratumoral or contra-lateral immunization of these DCs not only inhibited the growth of established tumors, but also eradicated tumors in more than 60% of tumor-bearing mice. Conclusion: Our data indicate that production of IL-12, chemokine receptor expression and NK as well as CTL activation may serve as major parameters in assessing the effect of tumor cell-pulsed DC vaccine. Therefore, DCs loaded with necrotic tumor cells offer a rational strategy to treat tumors and eventually lead to prolonged survival.
Pleomorphic adenoma is the most common benign tumor in salivary glands, and occurred in frequency of 60% in parotid gland tumors, and 50% in submandibular gland tumors, and 25% in sublingual gland tumors. Histopathologically, pleomorphic adenoma is composed of epithelial cells and mesenchymal tissues, and called 'mixed tumor' because of morphological divergency. The cell structures of luminal area are composed of polyhedral and cuboidal secretory epithelial cells and modified myoepithelial cells around it, and mesenchymal tissue is composed of some myoepithelial cells and stromal tissue. In stromal tissue, myxoid change, chondroid change, or hyalinization can be seen even if bone tissue. In many studies, tumor cells of pleomorphic adenoma containing modified myoepithelial cell participate in synthesis of glycosaminoglycans. In this study, tissue sample of pleomorphic adenoma of human salivary gland were obtained from 20 surgical specimens, and all specimens were routinely fixed in 10% formalin and embedded. Serial 4-8${\mu}m$ thick sections were cut from paraffin blocks. The histopathologic evaluation was done with light microscopy. And, with immunohistochemical staining, characteristics of glycosaminoglycan were observed. And, for biochemical analysis of glycosaminoglycan, isolation of crude glycosaminoglycan from tumor tissue and immuno-blot analysis were carried out. With transmission electromicroscopy, tumor cells and biologic behavior of pleomorphic adenoma were observed with distribution and expression of glycosaminoglycan in tumor cells, The results were obtained as follows: 1. In immunohistochemical study, chondroitin 4-sulfate is highly postively stained in myxoid stromal tissue, and chondroitin 6-sulfate is highly positively stained in chondroid mesenchymal tissue, both glycosaminoglycans are positively stained in non-luminal cell of ductal area. 2. Dermatan sulfate and keratan sulfate is positively stained in periductal non-luminal tumor cells. 3. In immunohistochemical study, heparan sulfate is weakly stained in luminal cells and non-luminal cells around duct, and chondroid mesenchymal tissue. 4. In transmission electromicroscopic view, the tumor cells are composed of modified myoepithelial cells, and contain many microfilaments and well developed rough endoplasmic reticulum. 5. In Immuno-Blot analysis, the expression of glycosaminoglycans is expressed mostly in chondroitin 6-sulfate and chondroitin 4-sulfate. From the results obtained in this study, tumor cells of pleomorphic adenoma are composed of modified myoepithelial cells, and glycosaminoglycans of chondroitin 4-sulfate and chondroitin 6-sulfate mostly participate in the development of pleomorphic adenoma, but dermatan sulfate, keratan sulfate and heparan sulfate glycosaminoglycans were expressed variably.
The Journal of the Korean bone and joint tumor society
/
v.8
no.1
/
pp.12-19
/
2002
Purpose : Giant cell tumors(GCT) sometimes undergo malignant transformation after the radiotherapy, but very rarely do without radiotherapy. We reviewed the clinical experiences of the malignant transformation of GCT to suggest the guidelines for diagnosis and treatment of them. Materials and Methods : We examined four patients of pathologically proven malignant transformation of GCT, which occurred after the operative treatment alone without radiation, from September 1985 to January 2001. The mean follow-up period after the malignant transformation was 2.4 years(range, 1.3~4 years). Results : The mean time-interval from the initial diagnosis to the malignant transformation was 6.9 years(range, 2.2~13.5 years). The locations of tumors were soft tissues of proximal upper arm, proximal femur, distal femur and proximal tibia. The histology of malignant GCT was osteosarcoma in 3 cases and malignant fibrous histiocytoma in 1 case. Local recurrence developed in 1 patient and the pulmonary metastasis developed in 3 patients which transformed to osteosarcoma. Conclusion : Thorough sampling of the surgical specimen appears to be a very important factor for diagnosing the malignant transformation of GCT. In case of suspicion of malignancy in radiographs, the incisional biopsy should be followed by definite treatment rather than the improper resection.
Objective: To explore the prevalence of malignant tumors in the adult population through 2003-2014 in parts of the Aral Sea region: a zone of ecological disaster, a zone of ecological crisis and a zone of precritical conditions. Methods: The long-time average annual levels of cancer morbidity stratified by zones of the Aral Sea region and trends of long-time average annual incidence indicators of malignant tumors were identified. Leading cancer localizations in the adult population was established and associations between cancer incidence and environmental pollution were analyzed. In addition, associations between individual risk factors and cancer incidence in the adult population was established. Correlations between a hazard index and the cancer incidence in the adult population were calculated. Results: In all three Aral Sea regions, as well as in Zhanaarkinskii district, leading cancer in adult population was esophageal, stomach, tracheal, lung, hepatobiliary, and breast. Long-time average annual levels of cancer morbidity in adult population living in the Aral sea region is 1.5 times higher comparing to the control region. In particular, long-time average annual levels of cancer morbidity in adult population living in the zone of ecological disaster was 57.2% higher, in the zone of ecological crisis - 61.9% higher, and in the zone of precritical condition - 16.8% higher. Long-time average annual levels in the adult population of the Aral Sea region significantly exceeded control levels for brain and central nervous system cancer, cancer of bone and articular cartilage, and thyroid cancer. Conclusion: It has was established that the total cancer morbidity depended on the total hazard index associated with the inhalation of nickel and the combined cadmium intake (r=0.8).
The Journal of the Korean bone and joint tumor society
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v.15
no.2
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pp.111-121
/
2009
Background: Osteosarcoma is one of the most common primary malignant tumors of bone occurring mainly in children and adolescents. Although surgery combined with chemotherapy has markedly improved patient survival during the last years, the use of anticancer drugs is still associated with serious problem, such as the frequent acquisition of drug-resistant phenotypes and occurrence of "secondary malignancies". Several solid tumors display enhanced expression of matrix metalloproteinases (MMPs), and recently clinical trials have been initiated on MMP-inhibitors. On the other hand, bisphosphonates (BPs) are inhibitors of bone resorption, and widely used to treat osteoclast-mediated bone diseases. Also they appear to possess direct antitumor activity. Methods: One osteosarcoma cell line (U2OS) was treated with ibandronate (0, 0.1, 1, $10{\mu}M$) for 48 hours. Cell viabilities were determined using MTT assay, the mRNA levels of MMP-2 and MT1-MMP were detected by reverse-transcription polymerase chain reaction, the amount of MMP-2 and MT1-MMP protein were measured by Westernblot, the activities of MMP-2 were observed by Gelatin zymography, and Matrigel invasion assays were used to investigate the invasive potential of osteosarcoma cell lines before and after ibandronate treatment. Results: The invasiveness of U2OS cell line was reduced dose-dependently following 48 hour treatment of up to $10{\mu}M$ of the ibandronate at which concentration no cytotoxicity occurred. Furthermore, the gelatinolytic activities and protein and mRNA levels of MMP-2 and MT1-MMP were also suppressed by increasing ibandronate concentrations. Conclusion: Given that MMP-2 is instrumental in tumor cell invasion, it is very likely that the reduction in osteosarcoma cell invasion by ibandronate is a consequence, at least in part, of suppressed expression of both MMP-2 and MT1-MMP. Isolation of a molecule (s) responsible for the bisphosphonate inhibition of tumor cell invasion would pave the way for the development of a new generation of metastasis inhibitors.
The Journal of the Korean bone and joint tumor society
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v.9
no.1
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pp.84-92
/
2003
Purpose: To report two cases of bone tumors other than osteoid osteoma in the proximal femur and treated with percutaneous high frequency radioablation method. Cases: We reviewed two cases with intracortical chondroma and enchondroma in the femoral head retrospectively. The patient with intracortical chondroma was a thirty one year old woman and had suffered right hip pain of 1 year duration. The lesion was located in the head of right femur and treated with CT guided percutaneous high frequency radioablation after needle biopsy under general anesthesia. The symptom was gone immediately after the procedure and was discharged postop. 1 day. 15 months has passed without symptom recurrence. Second case having enchondroma, was 56 year old woman complaining of gluteal area pain for 3 months. Radiologic evaluation showed osteolytic lesion with sclerotic rim on the inferior portion of the left femoral head. She received a same therapy with CT guided radiofrequency ablation following needle biopsy. She reported dramatic pain relief after the procedure and was discharged postop. 1 day. No symptom has occurred for 3 months until now. Conclusion: We present 2 cases of bone tumor occurred in the hip joint area other than osteoid osteoma which were treated with CT guided radiofrequency ablation.
Park, Ji-Yeon;Jung, Won-Gyun;Lee, Jeong-Woo;Lee, Kyoung-Nam;Ahn, Kook-Jin;Hong, Se-Mie;Juh, Ra-Hyeong;Choe, Bo-Young;Suh, Tae-Suk
Progress in Medical Physics
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v.21
no.2
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pp.153-164
/
2010
To determine the clinical target volumes considering vascularity and cellularity of tumors, the software was developed for mapping of the analyzed biological clinical target volumes on anatomical images using regional cerebral blood volume (rCBV) maps and apparent diffusion coefficient (ADC) maps. The program provides the functions for integrated registrations using mutual information, affine transform and non-rigid registration. The registration accuracy is evaluated by the calculation of the overlapped ratio of segmented bone regions and average distance difference of contours between reference and registered images. The performance of the developed software was tested using multimodal images of a patient who has the residual tumor of high grade gliomas. Registration accuracy of about 74% and average 2.3 mm distance difference were calculated by the evaluation method of bone segmentation and contour extraction. The registration accuracy can be improved as higher as 4% by the manual adjustment functions. Advanced MR images are analyzed using color maps for rCBV maps and quantitative calculation based on region of interest (ROI) for ADC maps. Then, multi-parameters on the same voxels are plotted on plane and constitute the multi-functional parametric maps of which x and y axis representing rCBV and ADC values. According to the distributions of functional parameters, tumor regions showing the higher vascularity and cellularity are categorized according to the criteria corresponding malignant gliomas. Determined volumes reflecting pathological and physiological characteristics of tumors are marked on anatomical images. By applying the multi-functional images, errors arising from using one type of image would be reduced and local regions representing higher probability as tumor cells would be determined for radiation treatment plan. Biological tumor characteristics can be expressed using image registration and multi-functional parametric maps in the developed software. The software can be considered to delineate clinical target volumes using advanced MR images with anatomical images.
Park, Il-Hyung;Kim, Sin-Gun;Shin, Dong-Kyu;Ihn, Joo-Chul
The Journal of the Korean bone and joint tumor society
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v.1
no.1
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pp.7-16
/
1995
In countries where confucianism is popular, it is extremely hard to get fresh cadaver bone for allograft. Therefore in Korea, the reimplantation of resected autoclaved autogenous bone segments has been increasingly performed for limb reconstruction of extremities with malignancies. To preserve the bone morphogenetic protein and mechanical strength of heated bone, many studies have reported that pasteurization of bone is far better than autoclaving over $100^{\circ}C$. Based on this assumption, replacement with a pasteurized autogenous bone graft after resection of a malignant bone tumor was deemed feasible for reconstruction. However, little is known about how high a temperature and how much time for pasteurization is needed to make tumors completely necrotic and to maintain the mechanical strength of bone. Consequantly, experimental studies were carried out to test heat conductivity of human bone and torsional strength of porcine tibia after pasteurization. First, two pairs of human proximal tibia and distal femur were used. We used T-type thermocoples to check core temperature of the bone and a computerized data acquisition system to record results. Without reaming of the medullary cavity, in a $60^{\circ}C$-thermostatic saline tub, it took 32 minutes and 50 seconds to raise the core temperature of human proximal tibia from $20^{\circ}C$ to $58^{\circ}C$, and 30 minutes for distal femur. In a $80^{\circ}C$ saline tub, it took 12 minutes and 50 seconds for proximal tibia, and 11 minutes and 10 seconds for distal femur. In contrast, using porcine tibia whose cortical thickness is similar to that of human tibia, after reaming of the medullary canal, it took less than 3 minutes and 30 seconds in a $60^{\circ}C$ saline tub, less than 1 minute and 45 seconds in a $70^{\circ}C$ tub, and less than 1 minute in a $80^{\circ}C$ tub to elevate core temperature from $20^{\circ}C$ to $58^{\circ}C$. Second, based on data of the heat conductivity test, we compared the torsional strength before and after pasteurization. Twenty matched pairs of porcine tibia were used, The left one was used as a non-heated control group and the right one as a pasteurized experimental group. Wighout reaming of the medullary cavity, there was no statistical difference in torsional strength between the pasteurization of the $60^{\circ}C$-35minute and of $80^{\circ}C$-15minute. With reaming, we also found no statistical difference among pasteurization of $60^{\circ}C$-15 minute, of $70^{\circ}C$-15 minute, and of $80^{\circ}C$-15 minute groups. In conclusion, reaming of the medullary canal is very helpful in saving pasteurization time. And, in a $60^{\circ}C$ saline tub, no significant weakness in torsional strength occurs with pasteurization of the bone for up to 35 minutes. Also no significant weakness in torsional strength occurs with an exposure of 15 minutes to the $80^{\circ}C$ saline tub.
Osteochondroma is the one of the most benign tumors of the axial skeleton, but is rarely found in the facial bones. Typical facial features of condylar osteochondroma include striking facial asymmetry, malocclusion with openbite on the affected side, and prognathic deviation of the chin and crossbite to the contralateral side. In this case, twenty four year-old female showed facial asymmetry, chin deviation, openbite on the affected side but have no symptoms of pain or dysfunction. Concomitantly she had maxillary occlusal cant and hemimandibular hypertrophy. Panoramic radiograph showed radiopaque mass on right mandibular condyle extended along the lateral pterygoid muscle. Computed tomogram demonstrated enlarged condylar head and bony spur on posteromedial side of condyle and 99Tc bone scintigraphy showed a focal hot image. These findings were correspond with osteochondroma. The lesion was treated with condylectomy and residual facial asymmetry was corrected with 2-jaw orthognathic surgery. Herein, we report a case of osteochondroma of the mandibular condyle and accompanying facial asymmetry.
Seo, Go-Eun;Jeong, Ji-A;Song, Jun-Ho;Jeong, Tae-Yeong;Lee, Soo-Woon;Park, Sang-Jun
Maxillofacial Plastic and Reconstructive Surgery
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v.32
no.1
/
pp.86-88
/
2010
Oral metastatic tumors are uncommon and account for about 1% of malignant oral neoplasm. The metastatic lesions are common in breast, lung, kidney and thyroid cancer. About 20% of oral mucosal metastasis is founded before detection of primary lesions. Usually, the metastatic lesions of the oral cavity are involved in the jaw bone, especially mandible more than the oral soft tissues. We report a case diagnosed as the stomach cancer with mandible metastatic lesion looking like TMJ abscess.
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