Despite recent groundbreaking advances in multiple myeloma (MM) treatment, most MM patients ultimately experience relapse, and the relapse biology is not entirely understood. To define altered gene expression in MM relapse, gene expression profiles were examined and compared among 16 MM patients grouped by 12 months progression-free survival (PFS) after autologous stem cell transplantation. To maximize the difference between prognostic groups, patients at each end of the PFS spectrum (the four with the shortest PFS and four with the longest PFS) were chosen for additional analyses. We discovered that integrin-${\alpha}8$ (ITGA8) is highly expressed in MM patients with early relapse. The integrin family is well known to be involved in MM progression; however, the role of integrin-${\alpha}8$ is largely unknown. We functionally overexpressed integrin-${\alpha}8$ in MM cell lines, and surprisingly, stemness features including $HIF1{\alpha}$, VEGF, OCT4, and Nanog, as well as epithelial mesenchymal transition (EMT)-related phenotypes, including N-cadherin, Slug, Snail and CXCR4, were induced. These, consequently, enhanced migration and invasion abilities, which are crucial to MM pathogenesis. Moreover, the gain of integrin-${\alpha}8$ expression mediated drug resistance against melphalan and bortezomib, which are the main therapeutic agents in MM. The cBioPortal genomic database revealed that ITGA8 have significant tendency to co-occur with PDGFRA and PDGFRB and their mRNA expression were up-regulated in ITGA8 overexpressed MM cells. In summary, integrin-${\alpha}8$, which was up-regulated in MM of early relapse, mediates EMT-like phenotype, enhancing migration and invasion; therefore, it could serve as a potential marker of MM relapse and be a new therapeutic target.
Purpose: The purpose of this study is to evaluate the post-operative skeletal stability after surgical correction of patients with mandibular prognathism by bilateral sagittal split ramus osteotomy (BSSRO) and to evaluate the horizontal relapse tendency after the surgery. Methods: Twenty-six patients with Class III dental and skeletal malocclusion were selected for this retrospective study. Fifteen of them underwent BSSRO for mandibular setback and eleven of them underwent two-jaw surgery (Lefort I and BSSRO). In each patient, lateral cephalometric radiographs were taken pre-operatively, post-operatively within 1 week, and post-operatively after eight months. After tracing of the cephalometric radiographs, various parameters were measured. The analyses were done by linear measurement to evaluate the change in position of hard tissue B point, pogonion and mandibular plan angle by examination on lateral cephalograms. Results: The horizontal relapse rate was 27.1% at B point and 31.6% at pogonion in patients who underwent BSSRO. The horizontal relapse rate of the group where the amount of correction exceeded 10 mm was 25.69% at B point. Conclusion: There were no statistical differences on the magnitude of setback and direction of rotation of the mandible in mandibular stability. There were also no statistical differences between single mandibular surgery and two-jaw surgery for mandibular stability.
The Purpose of this study was to investigate the predictors of relapse in orthodontic treatment of skeletal Class III malocclusion in growing patients. A total of 55 patients were studied and all subjects were divided into two groups according to their stability in the post-treatment stage. Of the sample, 33 patients were included in the stable group and the remaining 22 were assigned to the relapse group. Cephalometric data of the pre-treatment stage was taken and compared between the stable and relapse group. The following results were obtained through t-test: 1. This study presented statistical evidence to show that the major skeletal determinant of prognosis in Class III orthodontic treatment was not anteroposterior discrepancy .but vertical discrepancy, especially within the AB-maxillo mandibular triangle. Vertical angular measurements that showed statistically significant differences were AB-MP and ODI(P<0.01) and the vortical ratio measurements were MP-P/AL and PP-P/AL(P<0.05). 2. Relapse tendency increased with the steep occlusal Plane, especially the steep lower occlusal plane. As to occlusal plane, there were statistically significant differences in OP(L)-PP, OP-PP, AB-OP(L) and Wits appraisal(P<0.05). This study claimed that anteroposterior discrepancy was not necessarily the proper criteria to predict relapse. Vertical discrepancy had a significant effect on post-treatment stability.
Journal of the Korean Association of Oral and Maxillofacial Surgeons
/
v.29
no.6
/
pp.407-420
/
2003
Purpose : The purpose of this study was to analyse the facial changes and factors contributing to then after bilateral sagittal split ramus osteotomy of mandibular prognathism. Materials and Methods : Forty patients with Class III dental and skeletal malocclusion who were treated with bilateral sagittal split ramus osteotomy were reviewed. Frontal and lateral cephalometric radiographs were taken preoperatively, immediate postoperatively and more than six months postoperatively in each patient. After tracing the cephalometric radiographs, various parameters were measured. Results : 1. Gonial angle at postoperative two days was decreased about $10.4^{\circ}$ than preoperatively and gonial angle at postoperative six months was increased about $6.8^{\circ}$ than postoperative two days. So, gonial angle at postoperative six months was decreased about $3.6^{\circ}$ than preoperative gonial angle. 2. Facial height postoperative two days was decreased about 0.8mm than preoperatively and facial height at postoperative six months was decreased about 0.7mm than postoperative two days. So, facial height at postoperative six months was decreased about 1.5mm than preoperative facial height. 3. Mandibular width postoperative two days was decreased about 1.0mm than preoperatively and mandibular width at postoperative six months was increased about 1.8mm than postoperative two days. So, mandibular width at postoperative six months was decreased about 2.8mm than preoperative mandibular width. 4. Amount of set back and mandibular plane angle were not influencing on relapse degree. Conclusion : It is thought that bilateral sagittal split ramus osteotomy in mandibular prognathic patients is effective to improve long face and steep gonial angle. More prudent operation and careful postoperative management is required to maintain stable face postoperatively. Further research for soft tissue changes and factors which are related with relapse is needed.
Journal of the Korean Association of Oral and Maxillofacial Surgeons
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v.36
no.1
/
pp.28-38
/
2010
The factors influencing the relapse and recurrence of skeletal deformity after the orthognathic surgery include various factors such as condylar deviation, the amount of mandibular set-back, stretching force by the soft tissues and muscles around the facial skeleton. The purpose of this report is to recognize and analyze the possible factors of reoperation after orthognathic surgery, due to early relapses. Six patients underwent reoperation after the orthognathic surgeries out of 110 patients from 2006 to 2009 were included in this study. In most cases, clincal signs of the insufficient occlusal stability, anterior open bite, and unilateral shifting of the mandible were founded within 2 weeks postoperatively. Although elastic traction was initiated in every case, inadequate correction made reoperation for these cases inevitable. The chief complaints of five cases were the protruded mandible combined with some degree of asymmetric face and in the other one case, it was asymmetric face only. Various factors were considered as a major cause of post-operative instability such as condylar sagging, counter-clockwise rotation of the mandibular segment, soft tissue tension related with asymmetrical mandibular set-back, preoperatively existing temporomandibular disorder (TMD), poor fabrication of the final wafer, and dual bite tendency of the patients.
This study was investigated the changes during treatment and retention period in the Class III malocclusion patients and explored the correlationship between factors that showed relapse tendencies and pre-treatment skeletal pattern and the changes during treatment period. Numbers of total sample were 24 and their Hellman's dental age at the start of treatment was over III B and were retained at least over 1 year 6 months. The following conclusion were obtained by comparing the differences between treatment period and retention period, and after analysing the correlationship of factors that manifested relapse tendencies. 1. The angles formed by FH plane and occlusal plane, FH plane and mandibular plane, and mandibular incisor and mandibular plane changes showed rebound effect during retention period and among them occlusal plane angle and IMPA show reverse correlationship. 2. Upward displacement of the occlusal plane at the end of treatment has returning tendency, is proportional to the displacement during treatment period, but the angle between maxillary and mandibular 1st molar to its basal bone have been constantlsy maintained during the retention period. 3. Mandibular plane decrease during retention period and downward backward rotation during treatment period show correlationship.
This study was intended to perform the relationships between mandibualr lateral deviation in facial asymmetry patients and morphology of the cranial vault. In 30 patients(males 14, female 16) using submento-vertical cephalograms that were taken in the pre-operaticve state and posteroanterioir cephalograms that were taken in centric occlusion before, immediate and long term after surgery. 1. Mean mandibular deviation was about $-3.12^{\circ}$and mean of absolute measurement was about $2.50^{\circ}$on the submento-vertical cephalograms. 2. On the submento-vertical cephalograms, there was no significant difference between non-deviation and deviation side but it had tendency that deviation side was larger than non-deviation side on the frontal portion of cranium(Y10 to Y6) and deviation side was smaller than non-deviation on the temporal portion of cranium(Y5, Y-1 to Y-5). 3. Mean mandibular deviation was about $1.40^{\circ}$and mean of absolute measurement was about $3.95^{\circ}$on the posteroanterioir cephalograms. 4. There was statistical significance on the influence of surgical change(PT2A-PT1A) to the relapse(PTLA-PT2A)(p<0.05). The more increasing of the change, the more relapse on the posteroanterioir cephalograms. 5. There was no statistical significance on the influence of degree of mandibular deviation to morphology of the cranium on the submento-vertical cephalograms. But it had tendency that the more mandibular deviation, the larger the non-deviation side on the anterior cranium and deviation side on the posterior cranium(p>0.05). 6. There was statistical significance on the influence of the degree of mandibular deviation on the posteroanterioir cephalograms to the difference between non-deviation and deviation side. The more increasing of mandibular deviation, the larger the non-deviation side on the Y4 to Y-6(p<0.05). 7. There was no statistical significance on the influence of difference between non-deviation and deviation side to the relapse on the posteroanterioir cephalograms. But it had tendency that the more increasing of the differece between non-deviation and deviation side, the more increasing the relapse on temporal of cranium.
Purpose: The purpose of this study was to evaluate postsurgical facial hard tissue stability after orthognathic surgery with/without posterior impaction in skeletal class III malocclusion patients, and to evaluate the horizontal relapse tendency, according to changes in anteroposterior discrepancy and occlusal planes. Methods: Ninety patients, who had undergone orthognathic surgery in Pusan National University Dental Hospital, were enrolled in this study. Three main groups were classified as follows: Thirty patients underwent mandibular setback bilateral sagittal split ramus osteotomy (BSSRO) only (BSSRO group, BG); another thirty patients underwent mandibular setback BSSRO and Le Fort I osteotomy with posterior impaction (posterior impaction group, PG); and another thirty patients underwent mandibular setback BSSRO and Le Fort I osteotomy without posterior impaction (non-posterior impaction group, NPG). Preoperative (T0), immediate postoperative (T1) and six-month follow-up period (T2) lateral cephalograms were taken, and various parameters were measured. The analyses were done by linear and angular measurements between T0-T1 and T1-T2, to evaluate postsurgical facial hard tissue stability. Results: Mean horizontal relapse rates were distributed from 11.81% to 19.08%, and there were significant postsurgical changes (0.52 mm~2.44 mm) at the B point in all 3 groups. But, there were no statistical differences on relapse rate among BG, PG and NPG patients. Conclusion: In this study, the postsurgical stabilities of BSSRO and Le Fort I osteotomy with/without posterior impaction in skeletal class III malocclusion patients were acceptable. There were no significant statistical differences in mandibular stability according to changes in anteroposterior discrepancy and occlusal planes.
Kim, Juhwan;Ham, Suji;Hong, Heeok;Moon, Changjong;Im, Heh-In
Molecules and Cells
/
v.39
no.9
/
pp.645-653
/
2016
Morphine is the most potent analgesic for chronic pain, but its clinical use has been limited by the opiate's innate tendency to produce tolerance, severe withdrawal symptoms and rewarding properties with a high risk of relapse. To understand the addictive properties of morphine, past studies have focused on relevant molecular and cellular changes in the brain, highlighting the functional roles of reward-related brain regions. Given the accumulated findings, a recent, emerging trend in morphine research is that of examining the dynamics of neuronal interactions in brain reward circuits under the influence of morphine action. In this review, we highlight recent findings on the roles of several reward circuits involved in morphine addiction based on pharmacological, molecular and physiological evidences.
Kim, Hyun-Soo;Kwon, Tae-Geon;Lee, Sang-Han;Kim, Chin-Su;Kang, Dong-Hwa;Jang, Hyun-Jung
Journal of the Korean Association of Oral and Maxillofacial Surgeons
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v.33
no.2
/
pp.152-161
/
2007
This study was conducted to patients visited oral maxillo-facial surgery, KNUH and the purpose of the study was to assess skeletal and dento-alveolar stability after surgical-orthodontic correction treated by skeletal Class III malocclusion patients with open bite versus non-open bite. This retrospective study was based on the examination of 40 patient, 19 males and 21 females, with a mean age 22.3 years. The patients were divided into two groups based on open bite and non-open bite skeletal Class III malocclusion patients. The cephalometric records of 40 skeletal Class III malocclusion patients (open bite: n = 18, non-open bite: n = 22) were examined at different time point, i.e. before surgery(T1), immediately after surgery(T2), one year after surgery(T3). Bilateral sagittal split ramus osteotomy was performed in 40 patients. Rigid internal fixation was standard method used in all patient. Through analysis and evaluation of the cephalometric records, we were able to achieve following results of post-surgical stability and relapse. 1. There was no significant statistical differences between open bite and non-open bite with skeletal Class III malocclusion patients in maxillary occlusal plane angle of pre-operative stage(p>0.05). 2. Mean vertical relapses of skeletal Class III malocclusion patients with open bite were $0.02{\pm}1.43mm$ at B point and $0.42{\pm}1.56mm$ at Pogonion point. In skeletal Class III malocclusion patients with non-open bite, $0.12{\pm}1.55mm$ at B point and $0.08{\pm}1.57mm$ at Pogonion point. There was no significant statistical differences between open bite and non-open bite with skeletal Class III malocclusion patients in vertical relapse(p>0.05). 3. Mean horizontal relapses of skeletal Class III malocclusion patients with open bite were $1.22{\pm}2.21mm$ at B point and $0.74{\pm}2.25mm$ at Pogonion point. In skeletal Class III malocclusion patients with non-open bite, $0.92{\pm}1.81mm$ at B point and $0.83{\pm}2.11mm$ at Pogonion point. There was no significant statistical differences between open bite and non-open bite with skeletal Class III malocclusion patients in horizontal relapse(p>0.05). 4. There were no significant statistical differences between open bite and non-open bite with skeletal Class III malocclusion patients in post-surgical mandibular stability(p>0.05). and we believe this is due to minimized mandibular condylar positional change using mandibular condylar positioning system and also rigid fixation using miniplate 5. Although there was no significant relapse tendency observed at chin points, according to the Pearson correlation analysis, the mandibular relapse was influenced by the amount of vertical and horizontal movement of mandibular set-back(p=0.05, r>0.304).
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