To study the effect of isoprenoid and aliphatic saturated alcohols as modificator on benzoic nitrogen mustard, the intermediate 4-[N,N-bis(2-chloroethyl) amino] benzoic acid 4 was prepared in four steps utilizing p-amino benzoic acid as the starting material. Target compounds were synthesized by the catalytic esterification of DCC/DMAP and the structures of the six new esters were characterized by elemental analysis, 1H NMR, 13C NMR and MS. Antitumor activities were evaluated in vitro using MTT assay. The result showed that some derivatives were more potent than the intermediate 4, and compound 5c modified with dodecanol exhibited similar activity to the commercial drug melphalan.
Aminobenzoates ; chemical synthesis ; pharmacology ; Animals ; Antineoplastic Agents, Alkylating ; chemical synthesis ; pharmacology ; CHO Cells ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cricetinae ; Cricetulus ; Humans ; Inhibitory Concentration 50 ; K562 Cells ; Melanoma, Experimental ; pathology ; Melphalan ; pharmacology ; Nitrogen Mustard Compounds ; chemical synthesis ; pharmacology

PURPOSE: Neuroblastoma is the second common solid tumor in chidhood and has the worst prognosis in stage IV case. To improve the future survival rate in this disease the clinical and laboratory characteristics of patients, the characteristics and chemosensitivity test of cultured neuroblastoma cells and the outcome were compared. METHODS: The clinical characteristics including age, urinary catecholamines, serum ferritin, neuron specific enolase, pathology, stage, and patient's outcome were evaluated in four neuroblastoma patients diagnosed at the Department of Pediatrics, Kyungpook National Univesity Hospital. The neuroblastoma cells obtained from tumor or bone marrow cells were cultured and used for immunobead test using mononuclear antibody, biochemical analysis, N-myc oncogene copy, chromosome study and chemosensitivity test. Cyclophosphamide, cisplatin, doxorubicin, etoposide, ifosfamide and melphalan were used in chemosensitivity test. The statistical analyses were done by chi2-method. RESULTS: The age of patients were 6~31 (mean; 18) months. The adrenal gland was the primary site and the stage was IV in all cases. In laboratory data, serum ferritin level were 40~352 (204) ng/mL, neuron specific enolase 45~167 (107) ng/mL, urinary excretion of HVA 1.8~268 (73) mg/day, of VMA 0.2~345 (87) mg/day and the HVA/VMA ratio 0.8~67 (20). Cultured neuroblastoma cells and immunobeads attached around the cell were observed. The partial deletion of short arm or monosomy of chromosome 1, double minutes or homogenous stained region were found in three patients. N-myc oncogene copy was positive in one of two tested. Radical surgery was done in three patients and chemotherpy and radiotherpy by CCG-3881 or -3891 were given in four patients. The duration of survival in three died patients were 6~13 (mean; 10) months. One is survived in relapse-free state for 52 months. In chemosensitivity test, the neuroblastoma cell of survivor was highly sensitive in all drugs compared to the neuroblastoma cell of relapsed patients. CONCLUSION: Normal serum ferritin level or normal chromosome were correlated as a good prognostic factors in survivor compare in relapsed patients. In chemosensitivity test, the neuroblastoma cells of survivor were higher sensitive to all drugs compare to those of relapsed patients. The chemosensitivity test of this method were relatively simple and could be used in selection of anticancer drug and as a prognostic factor in neuroblastoma.
Adrenal Glands ; Arm ; Bone Marrow Cells ; Catecholamines ; Chromosomes, Human, Pair 1 ; Cisplatin ; Cyclophosphamide ; Doxorubicin ; Etoposide ; Ferritins ; Gyeongsangbuk-do ; Humans ; Ifosfamide ; Melphalan ; Monosomy ; Neuroblastoma* ; Oncogenes ; Pathology ; Pediatrics ; Phosphopyruvate Hydratase ; Prognosis ; Survival Rate ; Survivors

Antineoplastic Combined Chemotherapy Protocols ; Bendamustine Hydrochloride/therapeutic use* ; Etoposide ; Hematopoietic Stem Cell Transplantation ; Humans ; Lymphoma/therapy* ; Melphalan ; Transplantation Conditioning ; Transplantation, Autologous

No abstract available.
Ifosfamide*

No abstract available.
Ifosfamide*

BACKGROUND: Bendamustine is an attractive option for the management of both de novo and relapsed lymphomas. It is being increasingly used in the conditioning regimen for autologous stem cell transplantation (SCT) and can be an alternative to the traditionally-used carmustine. In this study, we aimed to determine the safety and efficacy of bendamustine in the conditioning regimen for autologous SCT in refractory/relapsed lymphomas. METHODS: We designed a descriptive study to evaluate bendamustine in combination with etoposide, cytarabine, and melphalan (BeEAM) in the conditioning regimen for autologous SCT. RESULTS: Fourteen patients (median age, 28 yr) with Hodgkin's lymphoma (HL) (N=8), non-Hodgkin's lymphomas (NHL) (N=5), or peripheral T-cell lymphoma, not otherwise specified (PTCL NOS) (N=1) were included in the study. A median number of 5.95×10⁶ CD34+ cells/kg were transfused. Median times to absolute neutrophil count and platelet engraftment were 17 days and 24 days, respectively. The 100-day transplantation mortality rate was 28% (4 patients). Eight patients (57.14%) had GII-III acute kidney injury, four patients (28.5%) had GIII-IV hyperbilirubinemia, and twelve patients (85%) had GII-III diarrhea. After 3 months, 37% (5 patients) and 21.4% (3 patients) demonstrated complete response and partial response, respectively. The median follow-up was 5.5 months (15 days–19 mo). At the final follow-up, 7 patients (50%) were alive and in CR. CONCLUSION: Our study showed that bendamustine is a potentially toxic agent in the conditioning regimen for autologous SCT, resulting in significant liver, kidney, and gastrointestinal toxicity. Further studies are required to assess its safety and efficacy at reduced doses.
Acute Kidney Injury ; Bendamustine Hydrochloride ; Blood Platelets ; Carmustine ; Cytarabine ; Diarrhea ; Etoposide ; Follow-Up Studies ; Hodgkin Disease ; Humans ; Hyperbilirubinemia ; Kidney ; Liver ; Lymphoma ; Lymphoma, Non-Hodgkin ; Lymphoma, T-Cell, Peripheral ; Melphalan ; Mortality ; Neutrophils ; Stem Cell Transplantation ; Stem Cells

PURPOSE: The objective of this study was to investigate the effects of calcium phosphate coated titanium implant surface on bone response and implant stability at early stage of healing period of 3 weeks and later healing period of 6 weeks. MATERIAL AND METHODS: A total of 24 machined, screw-shaped implants (Dentium Co., Ltd., Seoul, Korea) which dimensions were 3.3 mm in diameter and 5.0 mm in length, were used in this research. All implants (n = 24), made of commercially pure (grade IV) titanium, were divided into 2 groups. Twelve implants (n = 12) were machined without any surface modification (control). The test implants (n = 12) were anodized and coated with thin film (150 nm) of calcium phosphate by electron-beam deposition. The implants were placed on the proximal surface of the rabbit tibiae. The bone to implant contact (BIC) ratios was evaluated after 3 and 6 weeks of implant insertion. RESULTS: The BIC percentage of calcium phosphate coated implants (70.8 +/- 18.9%) was significantly higher than that of machined implants (44.1 +/- 16.5%) 3 weeks after implant insertion (P = 0.0264). However, there was no significant difference between the groups after 6 weeks of healing (P > .05). CONCLUSION: The histomorphometric evaluation of implant surface revealed that: 1. After 3 weeks early healing period, bone to implant contact (BIC) percentage of calcium phosphate coated implants (70.8%) was much greater than that of surface untreated machined implants (44.1%) with P = 0.0264. 2. After 6 weeks healing period, however, BIC percentage of calcium phosphate coated implants group (79.0%) was similar to the machined only implant group (78.6%). There was no statistical difference between two groups (P = 0.8074). 3. We found the significant deference between the control group and experimental group during the early healing period of 3 weeks. But no statistical difference was found between two groups during the later of 6 weeks.
Calcium ; Calcium Phosphates ; Nitrogen Mustard Compounds ; Tibia ; Titanium

PURPOSE: The purposes of this study were to investigate osseointegration around zirconia implants which had machined or alumina sandblasted surface, and to compare the results with titanium implants. MATERIALS AND METHODS: The study was performed on the tibia of 6 pigs. Three types of implants were investigated: group T-titanium implant, group Z-machined zirconia implant, group ZS-alumina sandblasting treated zirconia implant. Zirconia implants were manufactured from yttria-stabilized tetragonal zirconia polycrystalline (Acucera Inc., Pocheon, Korea). A total of 36 implants were installed in pigs' tibias. After 1, 4 and 12 weeks of healing period, the periotest and the histomorphometric analysis were performed. The data were analyzed using one-way ANOVA and significance was assessed by the Scheffe test (alpha=.05). RESULTS: In the measurement of surface roughness, highest Ra value was measured in group T with significant difference. No significant differences were found among groups regarding Periotest values. After 1 week, in comparison of bone to implant contact (BIC), group Z showed higher value with significant difference. In comparison of bone area (BA), group T and group Z showed higher value with significant difference than group ZS. After 4 weeks, in comparison of BIC, group T showed higher value with significant difference. Comparison of BA showed no significant difference among each implant. After 12 weeks, the highest mean BIC values were found in group T with significant difference. Group ZS showed higher BIC value with significant difference than group Z. In comparison of BA, group T and group ZS showed higher value with significant difference than group Z. CONCLUSION: Zirconia implant showed low levels of osseointegration in this experiment. Modification of surface structure should be taken into consideration in designing zirconia implants to improve the success rate.
Aluminum Oxide ; Nitrogen Mustard Compounds ; Osseointegration ; Swine ; Tibia ; Titanium ; Zirconium

OBJECTIVE: The purpose of this study was to evaluate the mobility and ratio of the bone-implant contact (BIC) of a sandblasted, large grit and acid-etched (SLA) orthodontic micro-implant. METHODS: Ninety-six micro-implants (48 SLA and 48 machined) were implanted in the upper and lower buccal alveolar bone, and palatal bone of four beagle dogs. Two weeks after surgery, orthodontic force (150 - 200 g) was applied. Two beagles were sacrificed at 4-weeks and the other two at 12-weeks. Histomorphometric comparisons were made between the SLA experimental group and the machined micro-implant as a control group to determine the ratio of contact between the bone and implant. Micro-implant mobility was also evaluated using Periotest(R). RESULTS: Periotest values showed no statistically significant difference in the upper alveolar and palatal bone between groups except for the lower buccal area. BIC in the upper buccal area showed no significant difference between groups both at 4-weeks and 12-weeks. However, both the groups showed a significant difference in BIC ratio in the rest of the experimental areas between 4 weeks and 12 weeks. The experimental group showed active bone remodeling around the bone-implant interface compared to the control group. CONCLUSIONS: There were significant differences in the BIC and the Periotest values between the surface-treated and machined micro-implants according to bone quality in the early stage.
Animals ; Bone Remodeling ; Dogs ; Nitrogen Mustard Compounds ; Osseointegration

OBJECTIVE: The purpose of this study was to investigate the stability of mini-implants in relation to loading time. METHODS: A total of 48 mini-implants (ORLUS, Ortholution, Korea) were placed into the buccal alveolar bone of the mandible in 8 male beagle dogs. Orthodontic force (200 - 250 gm) was applied immediately for the immediate loading group while force application was delayed for 3 weeks in the delayed loading group. For the subsequent loading periods (3, 6, 12 weeks), BIC (bone implant contact) and BV/TV (bone volume/total volume) and mobility test were carried out. RESULTS: The immediate loading group showed no changes in BIC from 3 to 12 weeks, while the delayed loading group showed a significant increase in BIC between 3 and 12 weeks (p < 0.05). The BV/TV of the delayed loading group significantly increased from 6 to 12 weeks of loading (p < 0.05), while the BV/TV of the immediate loading group decreased from 3 to 12 weeks of loading. However, there was no significant difference in BV/TV between experimental groups. The mobility of the immediate loading group was not significantly different from that of the delayed loading group after 12 weeks of loading (p < 0.05). CONCLUSIONS: These results showed that immediate loading does not have a negative effect on the stability of mini-implants compared to the early loading method in both the clinical and histomorphometric point of view.
Animals ; Dogs ; Humans ; Male ; Mandible ; Nitrogen Mustard Compounds