Background: High-dose methotrexate (HD-MTX) is recognized as an efficient component of therapy against pediatric osteosarcoma in combination with other drugs such as cisplatin (CDP), carboplatin (CBDCA), doxorubicin (ADM), etoposide (VP-16) and ifosfamide (IFO). Objectives: To demonstrate the feasibility and effectiveness of the HD-MTX/CDP/DOX/VP-16/IFO [MTX(+)] protocol comparable to CDP/ADM/CBDCA/IFO [MTX(-)] for treating childhood osteosarcoma at Ramathibodi Hospital (1999-2014). Materials and Methods: A retrospective analysis was conducted of osteosarcoma patients aged less than 18 years treated with two chemotherapeutic regimens between 1999 and 2014. A total of 45 patients received the MTX(-) and 21 the MTX(+) protocol. Results: Overall limb-salvage and amputation rate were 12.9% and 77.7%, respectively. Kaplan-Meier analysis results for 3-year disease free survival (DFS) and overall survival (OS) regardless of treatment regimens were $43.4{\pm}6.0%$ and $53.2{\pm}6.1%$ respectively. The 3-year DFS and OS were improved significantly with the MTX(+) protocol compared to MTX(-) protocol (p=0.010 and p=0.009, log rank test) [$69.8{\pm}10.5%$, $79.8{\pm}9.1%$ for MTX(+) and $31.1{\pm}6.9%$, $42.2{\pm}7.4%$ for MTX(-) protocol, respectively]. Patients with metastatic osteosarcoma treated with the MTX(+) protocol had statistically significant higher 3-year DFS and OS than those treated with the MTX(-) protocol ($66.7{\pm}13.6%$ and $15.0{\pm}8.0%$ for 3-year DFS, p=0.010, $73.3{\pm}13.2%$ and $20{\pm}8.9%$ for 3-year OS, p=0.006, respectively). The independent risk factors for having inferior 3-year DFS and OS were poor histological response (tumor necrosis <90%) and treatment with the MTX(-) protocol. The multivariate analysis identified only the treatment with the MTX(-) protocol as an independent predictor of inferior OS with a hazard ratio (HR) of 3.53 (95% confidence interval of 1.2-10.41, p=0.022). Conclusions: Our study demonstrated the tolerability, feasibility and efficacy of the HDMTX-based regimen improving the survival rate in pediatric osteosarcoma cases, in line with reports from developed countries.
Objectives : The aim of this study was to investigate the effect of Asthma-depression and Immunoregulation with PR-HAS(Herbal-acupuncture with Platycodi Radix infusion solution) injection at Joksamni(St36) on ovalbumin-induced asthma in mice. Methods : C57BL/6 mice were sensitized and challenged with OVA(ovalbumin) for 12 weeks(once a week). The experimental group(OVA-PR-HA) wase treated with concentrations(1%) of PR-HAS at Joksamni(St36) for the later 8 weeks(3times/week). The second experimental group(OVA-Needle prick) was treated with Needle-Prick at Joksamni(St36) for the later 8 weeks(3times/week). Results : 1. The weight and total cells in the mice lung treated with PR-HA decreased significantly compared with that of control group. 2. Total leukocytes and eosinophils in BALF of the mice group treated with PR-HA decreased remarkably compared with those of control group. 3. The sticking of collagen on histological analysis of lung sections, the mice group treated with PR-HA decreased significantly compared with those of control group. 4. The concentrations of IL-4, IL-5, IgE in BALF, and IL-4, IL-5, IL-13 in serum of the mice group treated with PR-HA decreased significantly compared with those of control group. 5. The number of $Gr-1^+/CD11b^+\;and\;CD11b^+$ cells in the lungs of the mice group treated with PR-HA decreased significantly compared with that of control group. 6. The numbers of $CCR3^+\;cells,\;CD4^+\;cells\;and\;CD8^+\;cells$ in the lungs, and $CD3e^+/CD69^+$ in the lungs of the mice group treated with PR-HA decreased significantly compared with those of control group. 7. The mRNA expression of ${\beta}-actin,\;TNF-{\alpha}$, IL-4, IL-5,IL-13 in the mice group treated with PR-HA with RT-PCR decreased significantly compared with those of control group. Conclusion : The concentrations of IL-4, IL-5, IgE in BALF, and IL-4, IL-5, IL-13 in serum of the mice group treated with PR-HA decreased significantly compared with those of control group. The number of $Gr-1^+/CD11b^+\;and\;CD11b^+$ cells in the lungs of the mice group treated with PR-HA decreased significantly compared with that of control group. The numbers of $CCR3^+\;cells,\;CD4^+\;cells\;and\;CD8^+\;cells$ in the lungs, and $CD3e^+/CD69^+$ in the lungs of the mice group treated with PR-HA decreased significantly compared with those of control group. The mRNA expression of ${\beta}-actin,\;TNF-{\alpha}$, IL-4, IL-5, IL-13 in the mice group treated with PR-HA with RT-PCR decreased significantly compared with those of control group. These result suggests that Platycodi Radix Herbal-acupuncture at Joksamni(St36) in C57BL/6mice may be an effictive part to OVA-induced asthma in C57BL/6 mice.
Histological observation on the seasonal variation of mucus cells of the mud loach Misgurnus mizolepis inhabiting a natural stream was carried out on three skin regions (dorsal, lateral and occiput) from March 2008 to February 2009. Our results showed no differences in general morphology by season, but the mucus cells of the epidermis showed significant seasonal change in their size and number as the water temperature changed. The ratio of surface area of the mucus cell layer and mucus cells, and the number of mucus cells in surface area of the epidermis were the greatest in the cold winter and the least in the hot summer in all regions of the epidermis. In particular, the occiput seemed to be a very sensitive region in response to environmental change, showing wide fluctuations in the size of mucus cells throughout the year and a great change in between seasons, especially from late autumn to early winter when the temperature decreased. As the temperature became colder, a small and spherical-shaped mucus cell was transformed into a large and elongated columnar form with a lot of secreted mucus material in a superficial layer of the epidermis. From our results, we can safely surmise that cold temperature is an important environmental factor having a close relationship with the modification of mucus cells of M. mizolepis in winter.
dos Santos, Pamela Leticia;de Molon, Rafael Scaf;Queiroz, Thallita Pereira;Okamoto, Roberta;de Souza Faloni, Ana Paula;Gulinelli, Jessica Lemos;Luvizuto, Eloa Rodrigues;Garcia, Idelmo Rangel Junior
Journal of Periodontal and Implant Science
/
v.46
no.3
/
pp.176-196
/
2016
Purpose: We sought to evaluate the effectiveness of bone substitutes in circumferential periimplant defects created in the rabbit tibia. Methods: Thirty rabbits received 45 implants in their left and right tibia. A circumferential bone defect (6.1 mm in diameter/4 mm depth) was created in each rabbit tibia using a trephine bur. A dental implant ($4.1mm{\times}8.5mm$) was installed after the creation of the defect, providing a 2-mm gap. The bone defect gaps between the implant and the bone were randomly filled according to the following groups: blood clot (CO), particulate Bio-Oss$^{(R)}$ (BI), and Bio-Oss$^{(R)}$ Collagen (BC). Ten animals were euthanized after periods of 15, 30, and 60 days. Biomechanical analysis by means of the removal torque of the implants, as well as histologic and immunohistochemical analyses for protein expression of osteocalcin (OC), Runx2, OPG, RANKL, and TRAP were evaluated. Results: For biomechanics, BC showed a better biological response ($61.00{\pm}15.28Ncm$) than CO ($31.60{\pm}14.38Ncm$) at 30 days. Immunohistochemical analysis showed significantly different OC expression in CO and BC at 15 days, and also between the CO and BI groups, and between the CO and BC groups at 60 days. After 15 days, Runx2 expression was significantly different in the BI group compared to the CO and BC groups. RANKL expression was significantly different in the BI and CO groups and between the BI and BC groups at 15 days, and also between the BI and CO groups at 60 days. OPG expression was significantly higher at 60 days postoperatively in the BI group than the CO group. Conclusions: Collectively, our data indicate that, compared to CO and BI, BC offered better bone healing, which was characterized by greater RUNX2, OC, and OPG immunolabeling, and required greater reversal torque for implant removal. Indeed, along with BI, BC presents promising biomechanical and biological properties supporting its possible use in osteoconductive grafts for filling peri-implant gaps.
Park, Soo-Ran;Park, Yang-Ho;Park, Young-Ju;Park, Jun-Woo;Lee, Yong-Chan;Ahn, Byoung-Keun
Journal of the Korean Association of Oral and Maxillofacial Surgeons
/
v.28
no.4
/
pp.302-309
/
2002
In order to improve the success rate of implants, various implant designs have been developed. Although there have been enough efforts to handle the surface of the implant with careful choice of material and mechanics so that the bone and the implant can be tightly joined together, they have still failed to play the role of periodontal ligaments of the natural teeth in the past. The role of periodontal ligaments is very important since it can improve the initial stability of implant by absorbing the impacts. The purpose of this study is, thus, to test the possibility of alleviating the impact when the surface of the implant was coated with chitosan, a natural polymer, and making sure that the coated material stayed on. Then, the condition of newly developed bone formation and the degree of inflammation in response was closely observed in the surface level. In the main experiment, Chitosan coated implant ($3.3mm{\times}7mm$) was implanted on both the right and the left side of rabbit's femur. The animals were each sacrificed on the $1^{st}$, $2^{nd}$, $3^{rd}$, $7^{th}$, $14^{th}$, $21^{st}$ and 28th day. The process was observed under an light microscope after the Toluidin Blue staining. From the experiment, it was found that the chitosan was evenly distributed on the surface of the screws, and the implant was adjoined with adjacent bone. There was a sign of inflammation on the $3^{rd}$ day, but on the $14^{th}$ day, the formation of woven bone and newly formed bones were noticed. Also, chitosan filled the gap was formed between the implant and the newly formed bone. The implant, the chitosan and the newly formed bone were forming one unit as a result. Therefore, it was found that chitosan coated implant could absorbe the impact in the initial stage of implant.
Kim, Sung Nam;Noh, Bok Kyun;Kim, Eui Sik;Hwang, Jae Ha;Kim, Kwang Seog;Lee, Sam Yong;Cho, Bek Hyun
Archives of Plastic Surgery
/
v.33
no.2
/
pp.219-224
/
2006
Augmentation rhinoplasty is one of the most popular aesthetic procedure in Asians. Numerous alloplastic implants have been used until now, but no accurate comparative analysis about the implant materials has been reported yet. This study in animal model was designed to determine the safety and effectiveness of various implant materials in augmentation rhinoplasty. The $15{\times}15{\times}2mm$ sized square shaped plate of $Gore-Tex^{(R)}$, silicone rubber, and $15{\times}15{\times}1.5mm$ sized $Medpor^{(R)}$ were implanted under panniculus carnosus of the abdomen wall of rat. And tissue specimens including the implant and surrounding soft tissue were obtained by en bloc excision in 6 months after implantation. The implants were estimated in weight and volume, and also the specimens were examined grossly and microscopically. The results revealed that increase of average weight 26.9%, decrease of average volume 55.4% in $Gore-Tex^{(R)}$ implant, increase of each average weight and volume 62.6%, 8.7% in $Medpor^{(R)}$ implant and very slight increase of both average weight and volume 4.7%, 1.1% in silicone rubber implant. Grossly, the $Gore-Tex^{(R)}$ was deformed, $Medpor^{(R)}$ was strongly adherent to surrounding soft tissue and the silicone rubber was well encapsulated and easily peeled off. Microscopically, silicone rubber showed foreign body reaction slightly and there were no inflammatory responses in all alloplastic implants. In our study, silicone rubber showed very proper alloplastic features for augmentation rhinoplasty due to causing no inflammatory response, no physical change, and no deformity.
Sung, Yong Duck;Kim, Yong Ha;Moon, Young Mi;Kim, Kap Joong;Kim, Yeon Jung;Choi, Sik Young
Archives of Plastic Surgery
/
v.34
no.3
/
pp.298-304
/
2007
Purpose: This study was undertaken to investigate the osteogenic induction potential of PGA & FBS mixture on a calvarial defect in the rabbit. Methods: Twenty New zealand white rabbit, weighing from 3.5-4kg were allocated into each of the three groups. Four 8 mm sized bone defects were made on the parietal bone by drilling. In group I, the bony defects were implanted with $50{\mu}m$ thickness film containing mixture of PGA and FBS. In group II, with PGA only film, & in group III, the bony defects were left with no implants. Results were evaluated by using morphologic change, radiographic study, biochemical study and histologic examination at 1 week (group I n=7, group II n=7, group III n=14), 2 weeks (group I n=6, group II n=6, group III n=12) and 3 weeks (group I n=7, group II n=7, group III n=14) following implantation. Results: In the morphologic & radiographic study, the formation and corticalization of callus were observed earlier in group I than in groups II and III (p < 0.05). In histological examination, group I showed more abundant and faster new bone formation than in group II and III. In biochemical analysis, group I displayed more activity than in group II and III. Group I also showed more abundant osteopontin, osteocalcin than groups II and III. Conclusion: In conclusion, the results demonstrate that the mixture of PGA and FBS has an effect on osteoblastic formation in the rabbit model. It is considered that further evaluation of long term results on resorption, immunologic tissue reaction and response of applied mixture in the human model will be needed.
The synergistic effect of combining radiation therapy and hyperthermia kills significantly more cells than using either modality alone. The reason for enhanced cell killing from the combined treatment is that the two modalities are complementary. For histopathological exmination, 102 rats were divided into 4 groups as hyperthermia, radiation, hyperthermia combined with radiation and normal control groups. The effect of prior irradiation (6-15 Gy of X-ray) on the response of small and large bowel of rats to $40^{\circ}C-44^{\circ}C$ (for 30 minutes) microwave (2450 MHz) hyperthermia was investigated. The musculature of the small and large intestine remained intact and the circumference of the histological sections were not significantly altered by the heated at $43^{\circ}C$ for 30 minutes. Thermal enhancement ratios of normal tissue is 1.0 Thermal enhancement ratio was not increased in combination therapy by evaluation of histopathologic changes in small and large intestine.
Park, Seungjo;Kwon, Seong-young;Min, Jung-Joon;Choi, Jihye
Journal of Veterinary Clinics
/
v.33
no.1
/
pp.51-57
/
2016
In this study, the features of canine lymphoma on fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) were evaluated in three small breed dogs. In case 1, ultrasonography and CT indicated neoplastic involvement of the sternal, right axillary, submandibular, lower cervical, tracheobronchial, mesenteric, and sublumbar lymph nodes; spleen; and liver. However, intense FDG uptake on PET/CT images was detected only for the lymph nodes and spleen. No FDG uptake by the liver was detected for case 1 despite the confirmation of lymphoma by cytology. In case 2, ultrasonography and CT indicated neoplastic involvement of the axillary, mesenteric, and sublumbar lymph nodes and the spleen, while intense FDG uptake on PET/CT images was detected for the axillary and a few mesenteric lymph nodes, and the spleen. FDG uptake was additionally observed from popliteal lymph nodes, however there was no uptake by the sublumbar lymph nodes and some mesenteric lymph nodes. In case 3, neoplastic changes in the splenic, mesenteric, and sublumbar lymph nodes and spleen were suspected on ultrasonography, and lower cervical and popliteal lymph node involvements were additionally detected on PET/CT. Compared to ultrasonography, repeated PET/CT showed increased FDG uptake by the lymph nodes at an earlier stage after chemotherapy in case 3. This study illustrated the features of PET/CT in canine lymphomas and compared those to ultrasonography and CT findings. FDG uptakes were not detected from some lesions which were suspected to be neoplastic involvement in case 1 and 2. We could not clearly explain the reason of this result in the present study because cytological or histological examination was not performed for lesions that showed different results on ultrasonography, CT, and PET/CT. Further studies on the subclassification of canine lymphoma and the sensitivity and specificity of PET/CT for the detection of canine lymphoma are required. PET/CT data can provide useful information for predicting the therapeutic response at an early stage after treatment.
Journal of Physiology & Pathology in Korean Medicine
/
v.20
no.3
/
pp.609-616
/
2006
The aim of this study was to investigate the effect of SR-HA(Stemonae Radix-herbal acupuncture) at Joksamni(ST36) on ovalbumin-induced asthma in mice. C57BL/6 mice were sensitized and challenged with OVA(ovalbumin) for 12 weeks(once a week). One of the two experimental groups was just treated with needle-prick on Joksamni(ST36) and the other group was treated with 1% concentrations of SR-HA at Joksamni(ST36) for the later 8 weeks (3times/week). The weight of lung of the mice group treated with SR-HA decreased significantly compared with those of control group, and significantly increased compared with those of normal group. The total cells of lung of the mice group treated with SR-HA decreased significantly compared with those of control group. Total leukocytes and eosinophils in BALF of the mice group treated wtih SR-HA decreased significantly compared with those of control group. Eosinophils in BALF of the mice group treated wtih SR-HA in Photomicrographs decreased significantly compared with those of control group. According to histological analysis of lung sections, adhesion of collagen in SR-HA decreased significantly compared with that of control group. The concentration of IgE, IL-4, IL-5 in BALF of the mice group treated with SR-HA decreased significantly compared with that of control group, and significantly increased compared with those of normal group. The concentration of IL-4, IL-5, IL-13 in serum of the mice group treated with SR-HA decreased significantly compared with that of control group, and significantly increased compared with those of normal group. The number of Gr-1+/CDl1b+, CO3-/CCR3+, CD4+, CD8+, CD3e+/CD69+ cells in the lungs of the mice group treated with SR-HA decreased significantly compared with those of control group. These results suggest that Stemonae Radix Herbal-acupuncture at Joksamni(ST36) in 057B146mice may be an effective part to OVA-induced asthma in C57BL/6 mice.
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