<ORIGINAL ARTICLE>Long-term follow-up of combined maxillary protraction appliance and chincap treatment

著しい骨格性反対咬合症例の治療において,我々は上顎前方牽引装置とchin capの併用により,顎関係の改善を行うことを含めた長期的管理を行っている。今回我々は骨格性反対咬合と診断され,治療を行った女子3症例の長期的観察を通し検討,考察を行った。これらの症例において,第一段階では上顎前方牽引装置とchin capにより顎関係を改善した。上顎前方牽引装置除去後,上顎は成長期間中位置変化を殆ど示さなかった。その間,下顎は予測よりも大きな成長を示した。咬合関係はすべての症例において成人期まで維持されていた。しかしこれらの症例は思春期成長の後も,下顎の前方成長により,わずかな後戻引頃向を示した。以上のことから,後戻りを予防するために反対咬合の治療においてはオーバーコレクションと第一段階後の下顎の成長のコントロールが必要であると考えられた。In an attempt to distinguish between long-term treatment effects and growth change, the present study evaluates the real post-treatment changes following maxillary protraction treatment after correction for the orthopedic effects which three female patients were investigated. Our proposed treatment plan for skeletal Class III patients consists of 3 stages. In the firststage, a maxillary protraction appliance and a chincap are used together to correct the intermaxillary relationship. After removal of the maxillary protraction appliance, the maxilla remains relatively stable during the growth stage. However, the mandible tends to experience overgrowth, which results in a relapse. The occlusal relationship was maintained until the adultstage in all cases. However, they experienced slight relapse, manifested by mandibular forward growth following removal of the maxillary protraction appliance. Therefore, overcorrection of reversed occlusion and control of mandibular growth after the first stage must be performed in order to prevent relapse

Gain-of-function oncogenic mutations in TP53 enhance defined factor-mediated cellular reprogramming

Cancer is a disorder with various genetic and epigenetic alterations. Genetic alterations such as mutations, i.e., substitutions, amplifications, and deletions of nucleotide sequences, are largely irreversible, whereas epigenetic alterations can be modified by pharmacological agents that target components of the epigenetic machinery. Recent studies have showed that introduction of defined factors such as those encoded by c-MYC, SOX2, OCT3/4, and KLF4 in normal somatic cells results in their dedifferentiation into induced pluripotent stem (iPS) cells. In addition, we have reported that these iPS factors induce the development of induced multipotent cancer (iPC) cells from gastrointestinal cancer cells by reducing tumor aggressiveness. The efficiency of iPS reprogramming increased when p53 was inhibited. The study of cancer cells suggests that the p53 pathways might be involved in the aggressive phenotypes of iPC cells in a long-term culture. However, the roles of gain-of-function oncogenic mutations in TP53, which is a key tumor suppressor gene, remain to be elucidated. We investigated reprogramming efficiency of iPS generation in human diploid fibroblasts that were co-transfected with TP53 mutants and defined factors. The results suggest that mutations in those TP53 regions that are involved in DNA contact might play a critical role in the efficiency of iPS generation. Taken together, our studies suggest 2 roles of TP53 mutations in reprogramming: (1) the structural mutations might contribute to, or collaborate with, other mutations to regulate the maintenance of genomic stability; (2) the DNA-contact mutations could affect the downstream target genes, which may be distinct from those involved in wild-type p53 function. These molecular manipulations of tumorigenicity and enhancement of cellular reprogramming efficiency by the p53 pathway will open an attractive and useful avenue for future medicine

Rad9 modulates the P21WAF1 pathway by direct association with p53

<p>Abstract</p> <p>Background</p> <p>Previous studies suggest that human <it>RAD9 </it>(hRad9), encoding a DNA damage checkpoint molecule, which is frequently amplified in epithelial tumor cells of breast, lung, head and neck cancer, participates in regulation of the tumor suppressor p53-dependent transactivation of pro-survival <it>P21</it>^{<it>WAF1</it>}. This study examined the exact mechanism of the hRad9 function, especially through the phosphorylation of the C-terminus, in the transcription regulation of <it>P21</it>^{<it>WAF1</it>}.</p> <p>Results</p> <p>The transfection of phosphorylation-defective <it>hRAD9 </it>mutants of C-terminus resulted in reduction of the p53-dependent <it>P21</it>^{<it>WAF1 </it>}transactivation; the knockdown of total hRad9 elicited an increased <it>P21</it>^{<it>WAF1 </it>}mRNA expression. Immunoprecipitation and a ChIP assay showed that hRad9 and p53 formed a complex and both were associated with two p53-consensus DNA-binding sequences in the 5' region of <it>P21</it>^{<it>WAF1 </it>}gene. The association was reduced in the experiment of phosphorylation-defective <it>hRAD9 </it>mutants.</p> <p>Conclusion</p> <p>The present study indicates the direct involvement of hRad9 in the p53-dependent <it>P21</it>^{<it>WAF1 </it>}transcriptional mechanism, presumably via the phosphorylation sites, and alterations of the hRad9 pathway might therefore contribute to the perturbation of checkpoint activation in cancer cells.</p

A four-dimensional organoid system to visualize cancer cell vascular invasion

Yanagisawa, K.; Konno, M.; Liu, H.; Irie, S.; Mizushima, T.; Mori, M.; Doki, Y.; Eguchi, H.; Matsusaki, M.; Ishii, H. A Four-Dimensional Organoid System to Visualize Cancer Cell Vascular Invasion. Biology 2020, 9, 361

RN7SL1 may be translated under oncogenic conditions

Hara T., Meng S., Tsuji Y., et al. RN7SL1 may be translated under oncogenic conditions. Proceedings of the National Academy of Sciences of the United States of America 121, (2024); https://doi.org/10.1073/pnas.2312322121.RN7SL1 (RNA component of signal recognition particle 7SL1), a component of the signal recognition particle, is a non-coding RNA possessing a small ORF (smORF). However, whether it is translated into peptides is unknown. Here, we generated the RN7SL1-Green Fluorescent Protein (GFP) gene, in which the smORF of RN7SL1 was replaced by GFP, introduced it into 293T cells, and observed cells emitting GFP fluorescence. Furthermore, RNA-seq of GFP-positive cells revealed that they were in an oncogenic state, suggesting that RN7SL1 smORF may be translated under special conditions

<ORIGINAL ARTICLE>The effects of sagittal ramus osteotomy for mandibular prognathism on maximum mouth opening and condylar movement

Maximum mouth opening and condylar movement before and more than 6 months after surgery were analyzed in 23 cases of sagittal ramus osteotomy of the mandible for correction of mandibular prognathism. Condylar movement (translation and rotation) did not show postoperatively a significant difference pre-and postoperatively, and then was a tendency to a reduction of maximum mouth opening was found

RNA Modification in Inflammatory Bowel Diseases

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder characterized by damage to the intestinal mucosa, which is caused by a combination of factors. These include genetic and epigenetic alterations, environmental influence, microorganism interactions, and immune conditions. Some populations with IBD show a cancer-prone phenotype. Recent studies have provided insight into the involvement of RNA modifications in the specific pathogenesis of IBD through regulation of RNA biology in epithelial and immune cells. Studies of several RNA modification-targeting reagents have shown preferable outcomes in patients with colitis. Here, we note a new awareness of RNA modification in the targeting of IBD and related diseases, which will contribute to early diagnosis, disease monitoring, and possible control by innovative therapeutic approaches

Convolutional neural network can recognize drug resistance of single cancer cells

It is known that single or isolated tumor cells enter cancer patients' circulatory systems. These circulating tumor cells (CTCs) are thought to be an effective tool for diagnosing cancer malignancy. However, handling CTC samples and evaluating CTC sequence analysis results are challenging. Recently, the convolutional neural network (CNN) model, a type of deep learning model, has been increasingly adopted for medical image analyses. However, it is controversial whether cell characteristics can be identified at the single-cell level by using machine learning methods. This study intends to verify whether an AI system could classify the sensitivity of anticancer drugs, based on cell morphology during culture. We constructed a CNN based on the VGG16 model that could predict the efficiency of antitumor drugs at the single-cell level. The machine learning revealed that our model could identify the effects of antitumor drugs with ~0.80 accuracies. Our results show that, in the future, realizing precision medicine to identify effective antitumor drugs for individual patients may be possible by extracting CTCs from blood and performing classification by using an AI system