ABSTRACT
Objective@#The purpose of this study was to investigate the accuracy of one-step automated orthodontic diagnosis of skeletodental discrepancies using a convolutional neural network (CNN) and lateral cephalogram images with different qualities from nationwide multi-hospitals. @*Methods@#Among 2,174 lateral cephalograms, 1,993 cephalograms from two hospitals were used for training and internal test sets and 181 cephalograms from eight other hospitals were used for an external test set. They were divided into three classification groups according to anteroposterior skeletal discrepancies (Class I, II, and III), vertical skeletal discrepancies (normodivergent, hypodivergent, and hyperdivergent patterns), and vertical dental discrepancies (normal overbite, deep bite, and open bite) as a gold standard. Pre-trained DenseNet-169 was used as a CNN classifier model. Diagnostic performance was evaluated by receiver operating characteristic (ROC) analysis, t-stochastic neighbor embedding (t-SNE), and gradientweighted class activation mapping (Grad-CAM). @*Results@#In the ROC analysis, the mean area under the curve and the mean accuracy of all classifications were high with both internal and external test sets (all, > 0.89 and > 0.80). In the t-SNE analysis, our model succeeded in creating good separation between three classification groups. Grad-CAM figures showed differences in the location and size of the focus areas between three classification groups in each diagnosis. @*Conclusions@#Since the accuracy of our model was validated with both internal and external test sets, it shows the possible usefulness of a one-step automated orthodontic diagnosis tool using a CNN model. However, it still needs technical improvement in terms of classifying vertical dental discrepancies.
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Objective@#To investigate demographic and skeletodental characteristics of one-jaw (1J-OGS) and two-jaw orthognathic surgery (2J-OGS) in patients with skeletal Class III malocclusion. @*Methods@#750 skeletal Class III patients who underwent OGS at 10 university hospitals in Korea between 2015 and 2019 were investigated; after dividing them into the 1J-OGS (n = 186) and 2J-OGS groups (n = 564), demographic and skeletodental characteristics were statistically analyzed. @*Results@#2J-OGS was more frequently performed than 1J-OGS (75.2 vs. 24.8%), despite regional differences (capital area vs. provinces, 86.6 vs. 30.7%, p 0.05). The most prevalent skeletal patterns in both groups were hyper-divergent pattern (50.0 and 54.4%, respectively) and left-side chin point deviation (both 49.5%).Maxillary spacing (odds ratio [OR], 3.645; p < 0.001) increased the probability of 2J-OGS, while maxillary crowding (OR, 0.672; p < 0.05) and normo-divergent pattern (OR, 0.615; p < 0.05) decreased the probability of 2J-OGS. @*Conclusions@#In both groups, males outnumbered females, and their mean operation age was older. The most frequent ALD was crowding in the 1J-OGS group, and spacing in the 2J-OGS group, while skeletal characteristics were not significantly different between the two groups.
ABSTRACT
Objective@#To investigate the pattern of accuracy change in artificial intelligence-assisted landmark identification (LI) using a convolutional neural network (CNN) algorithm in serial lateral cephalograms (Lat-cephs) of Class III (C-III) patients who underwent twojaw orthognathic surgery. @*Methods@#A total of 3,188 Lat-cephs of C-III patients were allocated into the training and validation sets (3,004 Lat-cephs of 751 patients) and test set (184 Lat-cephs of 46 patients; subdivided into the genioplasty and non-genioplasty groups, n = 23 per group) for LI. Each C-III patient in the test set had four Lat-cephs: initial (T0), pre-surgery (T1, presence of orthodontic brackets [OBs]), post-surgery (T2, presence of OBs and surgical plates and screws [S-PS]), and debonding (T3, presence of S-PS and fixed retainers [FR]). After mean errors of 20 landmarks between human gold standard and the CNN model were calculated, statistical analysis was performed. @*Results@#The total mean error was 1.17 mm without significant difference among the four timepoints (T0, 1.20 mm; T1, 1.14 mm; T2, 1.18 mm; T3, 1.15 mm). In comparison of two time-points ([T0, T1] vs. [T2, T3]), ANS, A point, and B point showed an increase in error (p < 0.01, 0.05, 0.01, respectively), while Mx6D and Md6D showeda decrease in error (all p < 0.01). No difference in errors existed at B point, Pogonion, Menton, Md1C, and Md1R between the genioplasty and non-genioplasty groups. @*Conclusions@#The CNN model can be used for LI in serial Lat-cephs despite the presence of OB, S-PS, FR, genioplasty, and bone remodeling.
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Objective@#To classify facial asymmetry (FA) phenotypes in adult patients with skeletal Class III (C-III) malocclusion. @*Methods@#A total of 120 C-III patients who underwent orthognathic surgery (OGS) and whose three-dimensional computed tomography images were taken one month prior to OGS were evaluated. Thirty hard tissue landmarks were identified. After measurement of 22 variables, including cant (°, mm), shift (mm), and yaw (°) of the maxilla, maxillary dentition (Max-dent), mandibular dentition, mandible, and mandibular border (Man-border) and differences in the frontal ramus angle (FRA, °) and ramus height (RH, mm), K-means cluster analysis was conducted using three variables (cant in the Max-dent [mm] and shift [mm] and yaw [°] in the Manborder). Statistical analyses were conducted to characterize the differences in the FA variables among the clusters. @*Results@#The FA phenotypes were classified into five types: 1) non-asymmetry type (35.8%); 2) maxillary-cant type (14.2%; severe cant of the Max-dent, mild shift of the Man-border); 3) mandibularshift and yaw type (16.7%; moderate shift and yaw of the Man-border, mild RH-difference); 4) complex type (9.2%; severe cant of the Max-dent, moderate cant, severe shift, and severe yaw of the Man-border, moderate differences in FRA and RH); and 5) maxillary reverse-cant type (24.2%; reverse-cant of the Max-dent). Strategic decompensation by pre-surgical orthodontic treatment and considerations for OGS planning were proposed according to the FA phenotypes. @*Conclusions@#This FA phenotype classification may be an effective tool for differential diagnosis and surgical planning for Class III patients with FA.
ABSTRACT
Heme oxygenase-1 (HO-1) is a critical stress-responsive enzyme that has antioxidant and anti-inflammatory functions. HO-1 catalyzes heme degradation, which gives rise to the formation of carbon monoxide (CO), biliverdin, and iron. The upregulation of HO-1 under pathological conditions associated with cellular stress represents an important cytoprotective defense mechanism by virtue of the anti-oxidant properties of the bilirubin and the anti-inflammatory effect of the CO produced. The same mechanism is hijacked by premalignant and cancerous cells. In recent years, however, there has been accumulating evidence supporting that the upregulation of HO-1 promotes cancer progression, independently of its catalytic activity. Such non-canonical functions of HO-1 are associated with its interaction with other proteins, particularly transcription factors. HO-1 also undergoes post-translational modifications that influence its stability, functional activity, cellular translocation, etc. HO-1 is normally present in the endoplasmic reticulum, but distinct subcellular localizations, especially in the nucleus, are observed in multiple cancers. The nuclear HO-1 modulates the activation of various transcription factors, which does not appear to be mediated by carbon monoxide and iron. This commentary summarizes the non-canonical functions of HO-1 in the context of cancer growth and progression and underlying regulatory mechanisms.
ABSTRACT
Cancer-associated fibroblasts (CAFs) represent a major component of the tumor microenvironment and interplay with cancer cells by secreting cytokines, growth factors and extracellular matrix proteins. When estrogen receptor-negative breast cancer MDAMB-231 cells were treated with the CAF-conditioned medium (CAF-CM), Akt and STAT3 involved in cell proliferation and survival were activated through phosphorylation. CAFs secrete fibroblast growth factor 2 (FGF2), thereby stimulating breast cancer cell progression. Akt activation induced by CAF-CM in MDA-MB-231 cells was abolished when FGF2-neutralizing antibody was added.Treatment of MDA-MB-231 cells directly with FGF2 enhanced the phosphorylation of Akt and the FGF receptor (FGFR) substrate, FRS2α. These events were abrogated by siRNA-mediated silencing of FGFR1. In a xenograft mouse model, co-injection of MDAMB-231 cells with activated fibroblasts expressing FGF2 dramatically enhanced activation of Akt. Stable knockdown of FGFR1 blunted Akt phosphorylation in xenograft tumors. MDA-MB-231 cells co-cultured with CAFs or directly stimulated with FGF2 exhibited enhanced nuclear localization of FGFR1. Notably, FGF2 stimulation produced reactive oxygen species (ROS) accumulation in MDA-MB-231 cells, and FGF2-induced nuclear accumulation of FGFR1 was abrogated by the ROS scavenging agent, N-acetylcysteine.
ABSTRACT
Background/Aims@#Heme oxygenase-1 (HO-1) plays a central role in cellular defense against inflammatory insults, and its induction in macrophages potentiates their efferocytic activity. In this study, we explored the potential role of macrophage HO-1 in the resolution of experimentally induced colitis. @*Methods@#To induce colitis, male C57BL/6 mice were treated with 2% dextran sulfate sodium (DSS) in the drinking water for 7 days. To investigate efferocytosis, apoptotic colon epithelial CCD 841 CoN cells were coincubated with bone marrow-derived macrophages (BMDMs). @*Results@#Administration of the HO-1 inhibitor zinc protoporphyrin IX (ZnPP) blunted the resolution of DSS-induced intestinal inflammation and expression of the proresolving M2 macrophage marker CD206. BMDMs treated with apoptotic colonic epithelial cells showed significantly elevated expression of HO-1 and its regulator Nrf2. Under the same experimental conditions, the proportion of CD206-expressing macrophages was also enhanced. ZnPP treatment abrogated the upregulation of CD206 expression in BMDMs engulfing apoptotic colonic epithelial cells. This result was verified with BMDMs isolated from HO-1-knockout mice. BMDMs, when stimulated with lipopolysaccharide, exhibited increased expression of CD86, a marker of M1 macrophages.Coculture of lipopolysaccharide-stimulated BMDMs with apoptotic colonic epithelial cell debris dampened the expression of CD86 as well as the pro-inflammatory cytokines in an HO-1-dependent manner. Genetic ablation as well as pharmacologic inhibition of HO-1 significantly reduced the proportion of efferocytic BMDMs expressing the scavenger receptor CD36. @*Conclusions@#HO-1 plays a key role in the resolution of experimentally induced colitis by modulating the polarization of macrophages.
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Background@#To identify work–family balance and level of happiness among married women dental hygienists in Seoul and Gyeonggi Province. The goal of this study is to use the outcome as basic data to determine the compatibility of dental hygienists with work and family, systems, and improvement of happiness levels. @*Methods@#From July 3 to August 10, 2020, 250 dental hygienists in Seoul and Gyeonggi Province were targeted. The questionnaire comprised 65 questions, including general characteristics (perception of work–family balance, perception of work–family balance system, job satisfaction, parenting type, happiness level) whether or not they were implemented. The results were obtained through a self-control questionnaire. @*Results@#The perception of work–family balance was significantly different in job rank and average income, while that of the work– family balance system had significant differences in workplace type, total work experience, current job work experience, childcare system status, and parental leave period. Happiness level and job satisfaction were significantly different in job rank, average income, and childcare system status. Additionally, the perception of work–family balance and that of the work–family balance system showed a positive correlation with job satisfaction and happiness level. Finally, the perception of married women dental hygienists toward work–family compatibility was determined, where the higher the satisfaction with the job, the higher the level of happiness. @*Conclusion@#To improve the work–family balance and job satisfaction of dental hygienists and their levels of happiness, changes in social perception and improvement of the working environment such as proper staffing, flexible work systems, and incentive systems should be considered.
ABSTRACT
Objective@#To evaluate the accuracy of a one-piece bracket jig system fabricated using computer-aided design and manufacturing (CAD/CAM) by employing three-dimensional (3D) digital superimposition. @*Methods@#This in vitro study included 226 anterior teeth selected from 20 patients undergoing orthodontic treatment. Bracket position errors from each of the 40 arches were analyzed quantitatively via 3D digital superimposition (best-fit algorithm) of the virtual bracket and actual bracket after indirect bonding, after accounting for possible variables that may affect accuracy, such as crowding and presence of the resin base. @*Results@#The device could transfer the bracket accurately to the desired position of the patient’s dentition within a clinically acceptable range of ± 0.05 mm and 2.0° for linear and angular measurements, respectively. The average linear measurements ranged from 0.029 to 0.101 mm. Among the angular measurements, rotation values showed the least deviation and ranged from 0.396° to 0.623°. Directional bias was pronounced in the vertical direction, and many brackets were bonded toward the occlusal surface. However, no statistical difference was found for the three angular measurement values (torque, angulation, and rotation) in any of the groups classified according to crowding. When the teeth were moderately crowded, the mesio-distal, bucco-lingual, and rotation measurement values were affected by the presence of the resin base. @*Conclusions@#The characteristics of the CAD/CAM one-piece jig system were demonstrated according to the influencing factors, and the transfer accuracy was verified to be within a clinically acceptable level for the indirect bracket bonding of anterior teeth.
ABSTRACT
Objective@#To investigate dimensional changes in regional pharyngeal airway spaces after premolar extraction in bimaxillary skeletal protrusion (BSP) patients according to vertical skeletal pattern, and to further identify dentoskeletal risk factors to predict posttreatment pharyngeal changes. @*Methods@#Fiftyfive adults showing BSP treated with microimplant anchorage after four premolar extractions were included in this retrospective study. The subjects were divided into two groups according to the mandibular plane steepness: hyperdivergent (Frankfort horizontal plane to mandibular plane [FH-MP] ≥ 30) and nonhyperdivergent groups (FH-MP < 0.01). The upper airway variable representing greater decrease in the hyperdivergent group than in the nonhyperdivergent group was the MAS (p < 0.01). Posttreatment changes in FH-MP had negative correlation with changes in MAS (β = –0.42, p < 0.01) and inferior airway space (β = –0.52, p < 0.01) as a result of multivariable regression analysis adjusted for sagittal skeletal relationship. @*Conclusions@#Decreased pharyngeal dimensions after treatment in BSP patients showed no significant difference from the normal range of pharyngeal dimensions. However, the glossopharyngeal airway space may be susceptible to treatment when vertical dimension increased in hyperdivergent BSP patients.
ABSTRACT
STAT3 plays a prominent role in proliferation and survival of tumor cells. Thus, STAT3 has been considered to be a prime target for development of anti-cancer therapeutics. The electrophilic cyclopentenone prostaglandin,15-deoxy-Δ12,14-prostaglandin J2(15d-PGJ2 ) has been well recognized for its capability to modulate intracellular signaling pathways involved in cancer cell growth and progression. We previously reported that 15d-PGJ2 had potent cytotoxicity against harvey-ras transformed human mammary epithelial cells through direct interaction with STAT3. In this study, we have attempted to verify the inhibitory effects of 15d-PGJ2 on STAT3 signaling in human breast tumor cells. The triple negative breast cancer cell lines, MDA-MB-231 and MDA-MB-468 displaying constitutive phosphorylation of STAT3 on the tyrosine 705 (Tyr705) residue, underwent apoptosis upon inhibition of STAT3 by 15d-PGJ2 . In contrast, estrogen receptor positive MCF-7 breast cancer cells that do not exhibit elevated STAT3 phosphorylation were much less susceptible to 15d-PGJ2 -induced apoptosis as assessed by PARP cleavage. Furthermore, 15d-PGJ2 inhibited interleukin-6-induced tyrosine phosphorylation of STAT3 in LNCaP cells. According to molecular docking studies, 15d-PGJ2 may preferentially bind to the cysteine 259 residue (Cys259) present in the coiled-coil domain of STAT3. Site-directed mutagenesis of STAT3 identified Cys259 to be the critical amino acid for the 15d-PGJ2 -induced apoptosis as well as epithelial-to-mesenchymal transition. Taken together, these findings suggest STAT3 inactivation through direct chemical modification of its Cys259 as a potential therapeutic approach for treatment of triple negative breast cancer treatment.
ABSTRACT
More than half of the world’s populations are considered to be infected by Helicobacter pylori. It causes a chronic inflammation of the stomach, which is implicated in the pathogenesis of gastric ulcer and cancer. Silibinin, a polyphenolic flavonoid derived from milk thistle, has been known for its hepatoprotective effects, and recent studies have revealed its chemopreventive potential. In the present study, we examined the anti-inflammatory effects of silibinin in human gastric cancer MKN-1 cells and in the stomach of C57BL/6 mice infected by H. pylori. Pretreatment with silibinin attenuated the up-regulation of COX-2 and inducible nitric oxide synthase (iNOS) in H. pylori-infected MKN-1 cells and mouse stomach. In addition, the elevated translocation and DNA binding of NFκB and STAT3 induced by H. pylori infection were inhibited by silibinin treatment. Moreover, H. pylori infection in combination with high salt diet resulted in dysplasia and hyperplasia in mouse stomach, and these pathological manifestations were substantially mitigated by silibinin administration. Taken together, these findings suggest that silibinin exerts anti-inflammatory effects against H. pylori infection through suppression of NF-κB and STAT3 and subsequently, expression of COX-2 and iNOS.
ABSTRACT
STAT3 plays a prominent role in proliferation and survival of tumor cells. Thus, STAT3 has been considered to be a prime target for development of anti-cancer therapeutics. The electrophilic cyclopentenone prostaglandin,15-deoxy-Δ12,14-prostaglandin J2(15d-PGJ2 ) has been well recognized for its capability to modulate intracellular signaling pathways involved in cancer cell growth and progression. We previously reported that 15d-PGJ2 had potent cytotoxicity against harvey-ras transformed human mammary epithelial cells through direct interaction with STAT3. In this study, we have attempted to verify the inhibitory effects of 15d-PGJ2 on STAT3 signaling in human breast tumor cells. The triple negative breast cancer cell lines, MDA-MB-231 and MDA-MB-468 displaying constitutive phosphorylation of STAT3 on the tyrosine 705 (Tyr705) residue, underwent apoptosis upon inhibition of STAT3 by 15d-PGJ2 . In contrast, estrogen receptor positive MCF-7 breast cancer cells that do not exhibit elevated STAT3 phosphorylation were much less susceptible to 15d-PGJ2 -induced apoptosis as assessed by PARP cleavage. Furthermore, 15d-PGJ2 inhibited interleukin-6-induced tyrosine phosphorylation of STAT3 in LNCaP cells. According to molecular docking studies, 15d-PGJ2 may preferentially bind to the cysteine 259 residue (Cys259) present in the coiled-coil domain of STAT3. Site-directed mutagenesis of STAT3 identified Cys259 to be the critical amino acid for the 15d-PGJ2 -induced apoptosis as well as epithelial-to-mesenchymal transition. Taken together, these findings suggest STAT3 inactivation through direct chemical modification of its Cys259 as a potential therapeutic approach for treatment of triple negative breast cancer treatment.
ABSTRACT
More than half of the world’s populations are considered to be infected by Helicobacter pylori. It causes a chronic inflammation of the stomach, which is implicated in the pathogenesis of gastric ulcer and cancer. Silibinin, a polyphenolic flavonoid derived from milk thistle, has been known for its hepatoprotective effects, and recent studies have revealed its chemopreventive potential. In the present study, we examined the anti-inflammatory effects of silibinin in human gastric cancer MKN-1 cells and in the stomach of C57BL/6 mice infected by H. pylori. Pretreatment with silibinin attenuated the up-regulation of COX-2 and inducible nitric oxide synthase (iNOS) in H. pylori-infected MKN-1 cells and mouse stomach. In addition, the elevated translocation and DNA binding of NFκB and STAT3 induced by H. pylori infection were inhibited by silibinin treatment. Moreover, H. pylori infection in combination with high salt diet resulted in dysplasia and hyperplasia in mouse stomach, and these pathological manifestations were substantially mitigated by silibinin administration. Taken together, these findings suggest that silibinin exerts anti-inflammatory effects against H. pylori infection through suppression of NF-κB and STAT3 and subsequently, expression of COX-2 and iNOS.
ABSTRACT
Objective@#To investigate dimensional changes in regional pharyngeal airway spaces after premolar extraction in bimaxillary skeletal protrusion (BSP) patients according to vertical skeletal pattern, and to further identify dentoskeletal risk factors to predict posttreatment pharyngeal changes. @*Methods@#Fiftyfive adults showing BSP treated with microimplant anchorage after four premolar extractions were included in this retrospective study. The subjects were divided into two groups according to the mandibular plane steepness: hyperdivergent (Frankfort horizontal plane to mandibular plane [FH-MP] ≥ 30) and nonhyperdivergent groups (FH-MP < 0.01). The upper airway variable representing greater decrease in the hyperdivergent group than in the nonhyperdivergent group was the MAS (p < 0.01). Posttreatment changes in FH-MP had negative correlation with changes in MAS (β = –0.42, p < 0.01) and inferior airway space (β = –0.52, p < 0.01) as a result of multivariable regression analysis adjusted for sagittal skeletal relationship. @*Conclusions@#Decreased pharyngeal dimensions after treatment in BSP patients showed no significant difference from the normal range of pharyngeal dimensions. However, the glossopharyngeal airway space may be susceptible to treatment when vertical dimension increased in hyperdivergent BSP patients.
ABSTRACT
Ascariasis is the most common helminthic infection in humans. However, its prevalence has been very low in Korea since the 1990s. Recently, there have been several case reports on intestinal obstruction or pancreaticobiliary disease due to infection with Ascaris lumbricoides in adults. However, cases of ascariasis in children have rarely been reported in Korea. We report a case of ascariasis in a 2-year-old boy who experienced expulsion of an adult ascaris worm from his anus. His mother found the worm in his diaper in the morning. His medical history was nonsignificant for any previous illnesses. There were no specific symptoms, and no abnormal findings were found on physical examination. The worm was pink, elongated, and cylindrical; it was 25 cm long and 5 mm wide. Unfertilized eggs of A. lumbricoides were detected in his stool specimen. He was treated with albendazole and remained asymptomatic at follow-up. As long as the number of immigrants from endemic areas and people returning from overseas trips, and import of agricultural products keep increasing, ascariasis can still occur in Korea. Therefore, it is necessary to raise awareness regarding ascariasis.
ABSTRACT
Objective@#Ceramide is a signaling molecule that contributes to insulin resistance and hepatosteatosis. In the present study, we activated de novo ceramide synthesis by inducing the hepatic expression of Sptlc2 to investigate the role of ceramide in glucose and lipid metabolism. @*Methods@#We first constructed an adenovirus containing Sptlc2 (AdSptlc2), which encodes a major catalytic subunit of serine palmitoyltransferase (SPT). We then infected hepatocytes and mice fed a regular diet with AdSptlc2 to activate de novo ceramide biosynthesis. The liver-specific effects of ceramide biosynthesis on glucose and lipid metabolism were investigated by measuring changes in insulin signaling, lipid droplet formation, and very low-density lipoprotein (VLDL) secretion. @*Results@#In HepG2 hepatocytes, adenoviral Sptlc2 expression inhibited insulin signaling and increased ceramide levels via activation of c-Jun N-terminal kinase and serine phosphorylation of insulin receptor substrate 1. In contrast, in mice, AdSptlc2 infection decreased plasma glucose levels by downregulating gluconeogenic genes and increased plasma triglyceride levels by increasing VLDL secretion. In mice infected with AdSptlc2, glucose intolerance and insulin sensitivity improved, while pyruvate utilization via gluconeogenesis decreased. @*Conclusion@#Hepatic ceramide was found to modulate hepatosteatosis and the insulin response via increased VLDL secretion and inhibition of gluconeogenesis in vivo. Although inhibition of the insulin response was observed in vitro, the compensatory mechanism of relieving ceramide-induced stress and reducing ceramide levels resulted in improvements of glucose and lipid metabolic profiles in vivo. This discrepancy between in vitro and in vivo regulation mechanisms suggests that ceramide plays a role in non-alcoholic fatty liver disease and insulin resistance.
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Objective@#To investigate the effects of the long-term use of a maxillary protraction facemask with miniplate (FM-MP) on pharyngeal airway dimensions in growing patients with cleft lip and palate (CLP). @*Methods@#The study included 24 boys with CLP (mean age, 12.2 years; mean duration of FM-MP therapy, 4.9 years), divided into two groups according to the amount of A point advancement to the vertical reference plane (VRP): Group 1, > 4 mm; Group 2, < 2 mm; n = 12/group. After evaluating the skeletodental and airway variables using lateral cephalograms acquired before and after FM-MP therapy, statistical analyses were performed. @*Results@#Group 1 showed greater forward and downward displacements of the posterior maxilla (posterior nasal spine [PNS]-horizontal reference plane [HRP]; PNSVRP), greater increase in ANB, more forward tongue position (tongue tip-Pt vertical line to Frankfort horizontal plane), and greater increase in the oropharynx (superior posterior airway space [SPAS]; middle airway space [MAS]) and upper nasopharynx (PNS-adenoid2) than did Group 2. While maxillary advancement (A-VRP and PNS-VRP) correlated with increases in SPAS, MAS, and PNS-adenoid2, downward displacement of the PNS (PNS-HRP) correlated with increases in SPAS, MAS, PNSadenoid1, and PNS-adenoid2, and with a decrease in vertical airway length (VAL). Mandibular forward displacement and decrease in mandibular plane correlated with increases in MAS. @*Conclusions@#FM-MP therapy had positive effects on the oropharyngeal and nasopharyngeal airway spaces without increases in VAL in Group 1 rather than in Group 2. However, further validation using an untreated control group is necessary.
ABSTRACT
Aberrant activation of Ras has been implicated in aggressiveness of breast cancer. Among Ras isoforms (H-, K-, and N-), H-Ras has been known to be primarily responsible for invasion and metastasis of breast cancer cells. Phosphorylation of serine (Ser) or threonine (Thr) is a key regulatory mechanism responsible for controlling activities and functions of various proteins involved in intracellular signal transduction. Peptidyl-prolyl Cis-trans isomerase NIMA-interacting 1, Pin1 changes the conformation of a subset of proteins phosphorylated on Ser/Thr that precedes proline (Pro). In this study we have found that Pin1 is highly overexpressed in human breast tumor tissues and H-Ras transformed human mammary epithelial (H-Ras MCF10A) and MDA-MB-231 breast cancer cells. Notably, Pin1 directly bound to the activated form of H-Ras harbouring a Ser/Thr-Pro motif. Pharmacologic inhibition of Pin1 reduced clonogenicity of MDA-MB-231 human breast cancer cells. Paclitaxel accelerates apoptosis in Pin1 silenced H-Ras MCF10A cells. MDR genes (MDR1 and MRP4) were significantly downregulated in MDA-MB-231 cells stably silenced for Pin1. We speculate that Pin1 interacts with GTP-H-Ras, thereby upregulating the expression of drug resistance genes, which confers survival advantage and aggressiveness of breast cancer cells under chemotherapy.
ABSTRACT
Aberrant activation of Ras has been implicated in aggressiveness of breast cancer. Among Ras isoforms (H-, K-, and N-), H-Ras has been known to be primarily responsible for invasion and metastasis of breast cancer cells. Phosphorylation of serine (Ser) or threonine (Thr) is a key regulatory mechanism responsible for controlling activities and functions of various proteins involved in intracellular signal transduction. Peptidyl-prolyl Cis-trans isomerase NIMA-interacting 1, Pin1 changes the conformation of a subset of proteins phosphorylated on Ser/Thr that precedes proline (Pro). In this study we have found that Pin1 is highly overexpressed in human breast tumor tissues and H-Ras transformed human mammary epithelial (H-Ras MCF10A) and MDA-MB-231 breast cancer cells. Notably, Pin1 directly bound to the activated form of H-Ras harbouring a Ser/Thr-Pro motif. Pharmacologic inhibition of Pin1 reduced clonogenicity of MDA-MB-231 human breast cancer cells. Paclitaxel accelerates apoptosis in Pin1 silenced H-Ras MCF10A cells. MDR genes (MDR1 and MRP4) were significantly downregulated in MDA-MB-231 cells stably silenced for Pin1. We speculate that Pin1 interacts with GTP-H-Ras, thereby upregulating the expression of drug resistance genes, which confers survival advantage and aggressiveness of breast cancer cells under chemotherapy.