RESUMEN
BACKGROUND: Cementoblastoma is a rare odontogenic tumor characterized by the formation of osteocementum-like tissue on a tooth root directly by neoplastic cementoblasts. Although it is categorized as benign, it has a high potential for growth with a certain degree of recurrence risk. However, there are only a few studies describing the features of recurrent cementoblastoma. The diagnosis of recurrent cementoblastoma is challenging not only due to its cytological atypia but also because of its large size and multicentric growth pattern. These characteristics suggest a potential for malignancy. CASE PRESENTATION: A 29-year-old woman was transferred to our university dental hospital complaining of swelling of the right mandible. She had a history of enucleation of cementoblastoma associated with the third molar of the right mandible. Five years after the initial treatment, imaging demonstrated well-circumscribed multicentric radiopaque lesions in the same area. Histologically, the lesion consisted of osteocementum-like tissue rimmed with polygonal or plump tumor cells. Several cells were large epithelioid cells with bizarre nucleoli, which may be reminiscent of malignant tumors. Otherwise, there were no apparent malignant findings, including proliferative activity or atypical mitotic figure. Besides, tumor cells were positive for c-FOS, a marker of osteoblastoma and cementoblastoma. Eventually, the patient was diagnosed with recurrent cementoblastoma. CONCLUSIONS: Pathological analyses of this case suggested that the recurrent event in the cementoblastoma altered its growth pattern and tumor cell shape. Moreover, in the case of enucleation surgery, long-term follow-up is important because there is some recurrent risk of cementoblastoma, although it is not high.
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Cementoma , Neoplasias Mandibulares , Tumores Odontogénicos , Femenino , Humanos , Adulto , Neoplasias Mandibulares/cirugía , Neoplasias Mandibulares/patología , Cementoma/diagnóstico , Cementoma/patología , Tumores Odontogénicos/cirugía , Tumores Odontogénicos/patología , Raíz del Diente/patología , Mandíbula/patologíaRESUMEN
BACKGROUND: Squamous cell carcinoma (SCC) is the most common oral malignancy, and somatic mutations in some driver genes have been implicated in SCC development. Clear cell SCC (CCSCC) is a rare histological variant of SCC, and various clear cell neoplasms must be considered in the differential diagnosis of CCSCC in the oral cavity. Based on a limited number of CCSCC cases reported in the oral cavity, CCSCC is considered an aggressive variant of SCC with a poor prognosis; however, its genetic characteristics remain unknown. METHODS: A maxillary gingival tumor in an 89-year-old female was described and investigated using immunohistochemical staining, special staining, fluorescence in situ hybridization, and next-generation sequencing (NGS) with a custom panel of driver genes, including those associated with SCC and clear cell neoplasm development. RESULTS: Histopathological examination revealed a proliferation of atypical epithelial cells with abundant clear cytoplasm and enlarged and centrally placed round nuclei. The tumor was exophytic with deep, penetrating proliferation. The atypical clear cells were continuous with the conventional SCC cells. Immunohistochemical analysis showed that the clear cells were positive for CK AE1/AE3 and CK5/6 and nuclear-positive for p63. In contrast, the clear cells were negative for αSMA, S100, HMB45, Melan-A, CD10, and p16. p53 immunoreactivity exhibited a wild-type expression pattern. Additionally, the clear cells were positive for periodic acid-Schiff (PAS) and negative for diastase-PAS, mucicarmine, and Alcian blue. Based on these results, the diagnosis of CCSCC was confirmed. Molecular analysis of the clear cells identified PIK3CA p.E542K (c.1624G>A) and HRAS p.G12A (c.35 G>C) somatic mutations classified as oncogenic. No pathogenic variants were identified in TP53, EWSR1, AKT1, PTEN, BRAF, KRAS, NRAS, RASA1, or MAML2. CONCLUSIONS: We report a case of CCSCC of the oral cavity with PIK3CA and HRAS mutations. The identification of PIK3CA and/or HRAS mutations is rare in SCC; however, both mutations are important potential targets for antitumor therapy. A detailed analysis of gene mutations in CCSCC may lead to a better understanding of its biological behavior and an improved prognosis, as well as a differential diagnosis from other clear cell neoplasms.
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Adenocarcinoma de Células Claras , Carcinoma de Células Escamosas , Femenino , Humanos , Anciano de 80 o más Años , Encía/patología , Hibridación Fluorescente in Situ , Carcinoma de Células Escamosas/patología , Mutación , Células Epiteliales/patología , Fosfatidilinositol 3-Quinasa Clase I/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteína Activadora de GTPasa p120/genética , Proteína Activadora de GTPasa p120/metabolismoRESUMEN
The main purpose of cytological examination in the oral region is to screen for squamous cell carcinoma or intraepithelial neoplasms; thus, the background tends to be considered a deterrent for microscopy. From this perspective, liquid-based cytology (LBC) is favorable for preparing clear samples with few backgrounds. However, background hemocytes are sometimes of critical importance in the diagnosis. We report two cases of oral malignant lymphoma, plasmablastic lymphoma, and anaplastic large cell lymphoma in which careful observation of the background in scraping LBC sample contributed to the early diagnosis. Atypical lymphoid cells were observed only in a very small part of the LBC samples from the presented patients; however, cytological findings, such as large lymphoid cells with outstanding nucleoli, large mitotic cells, or intermediate-to-large lymphoid cells with pleomorphic nuclei were sufficient for obtaining a cytological diagnosis of malignant lymphoma. Although the number and cell size of leukocytes in LBC with Papanicolaou staining were significantly different from those in air-dried conventional smears with Romanovsky staining, which are commonly preferred for the discrimination of hemocytes, the corresponding cytological features could be observed. Therefore, attention should be paid to the background as well as squamous epithelium to prepare for such unexpected cases. The LBC examination with Papanicolaou staining alone can suggest the possibility of malignant lymphoma.
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Linfoma Anaplásico de Células Grandes , Linfoma Plasmablástico , Neoplasias del Cuello Uterino , Humanos , Femenino , Linfoma Anaplásico de Células Grandes/diagnóstico , Linfoma Anaplásico de Células Grandes/patología , Linfoma Plasmablástico/patología , Quinasa de Linfoma Anaplásico , Citología , Citodiagnóstico , Neoplasias del Cuello Uterino/patologíaRESUMEN
Background/purpose: Diagnostic methods of oral squamous cell carcinoma (SCC) using artificial intelligence (AI) and digital-histopathologic images have been developed. However, previous AI training methods have focused on the cellular atypia given by the training of high-magnification images, and little attention has been paid to structural atypia provided by low-power wide fields. Since oral SCC has histopathologic types with bland cytology, both cellular atypia and structural atypia must be considered as histopathologic features. This study aimed to investigate AI ability to judge oral SCC in a novel training method considering cellular and structural atypia and their suitability. Materials and methods: We examined digitized histological whole-slide images from 90 randomly selected patients with tongue SCC who attended a dental hospital. Image patches of 1000 × 1000 pixels were cut from whole-slide images at 0.3125-, 1.25-, 5-, and 20-fold magnification, and 90,059 image patches were used for training and evaluation. These image patches were resized into 224 × 224, 384 × 384, 512 × 512, and 768 × 768 pixels, and the differences in input size were analyzed. EfficientNet B0 was utilized as the convolutional neural network model. Gradient-weighted class activation mapping (Grad-CAM) was used to elucidate its validity. Results: The proposed method achieved a peak accuracy of 99.65% with an input size of 512 × 512 pixels. Grad-CAM suggested that AI focused on both cellular and structural atypia of SCC, and tended to focus on the region surrounding the basal layer. Conclusion: Training AI regarding both cellular and structural atypia using various magnification images simultaneously may be suitable for the diagnosis of oral SCC.
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An ameloblastic fibroma with formation of dental hard tissues, which the classical name is ameloblastic fibro-odontoma (AFO), is a rare type of mixed odontogenic tumor. An 8-year-old boy was diagnosed with AFO, with an inhomogeneous high signal within the lesion shown by T2-weighted magnetic resonance imaging (MRI). Computed tomography (CT) imaging revealed a unilocular low CT value area of 24 × 19 × 26 mm with buccolingual bony expansion and cortical bone thinning on the left side of the mandible including the crown of the mandibular left second molar. In addition, multiple calcified bodies were detected within the lesion, one of which had a CT value of approximately 2200 HU, equivalent to that of enamel. MRI indicated the lesion to be sized 24 × 19 × 25 mm along with buccolingual bony expansion in the left side of the mandible. Additionally, the lesion showed an internal inhomogeneous high signal, while a portion had an especially high signal in T2-weighted images. That particularly high signal area coincided with the nodular growth area of mucus-rich mesenchymal components without the epithelial component in histopathology findings. The particularly high signal revealed by T2-weighted imaging could be attributed to the mucus-rich component. MRI was found useful for revealing differences in the internal histopathological properties of an AFO in our patient.
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Fibroma , Neoplasias Mandibulares , Tumores Odontogénicos , Odontoma , Masculino , Humanos , Niño , Neoplasias Mandibulares/diagnóstico por imagen , Neoplasias Mandibulares/patología , Tumores Odontogénicos/diagnóstico por imagen , Odontoma/diagnóstico por imagen , Odontoma/patología , Mandíbula/patología , Imagen por Resonancia MagnéticaRESUMEN
BACKGROUND: Orthokeratinized odontogenic cyst (OOC) is a rare developmental odontogenic cyst of the jaw. It was originally believed to be a variant of odontogenic keratocyst (OKC) but is now considered to be a distinct entity. OOC usually presents as a single lesion and recurs infrequently. On the other hand, OKC often presents with multiple lesions and displays locally aggressive behavior and a high recurrence rate associated with the protein patched homolog 1 (PTCH1) gene mutation. Multiple OOC cases are extremely rare and seem to be aggressive, but their pathogenesis is not fully understood. This study aimed to determine the clinical, pathological, and genetic characteristics of multiple OCC. METHODS: Three cases of multiple OOC were evaluated for clinical and histological findings, and immunohistochemical expression of Ki-67 and Bcl-2. Furthermore, PTCH1 mutations were analyzed by next-generation sequencing using a custom panel to cover the entire exon of PTCH1. RESULTS: The three cases of multiple OOC included two men and one woman with a mean age of 25.3 years old (range, 18-38 years old). Each case had two or three OOCs (total of seven OOCs), all of which were simultaneously detected. Of the seven OOCs that manifested as multiple jaw cysts, seven (100%) occurred in the posterior regions, four (57.1%) occurred in the mandible, and four (57.1%) were associated with an impacted tooth. Histological examination revealed cysts lined by orthokeratinized stratified squamous epithelium. Immunohistochemistry showed a low Ki-67 labeling index and no Bcl-2 expression in the seven OOCs. No pathogenic PTCH1 mutations were detected in any of the seven OOCs. None of the patients had any other symptoms or signs of recurrence at the last follow-up (6-60 months). CONCLUSION: Multiple OOCs appeared to occur more often in younger patients than solitary OOC. Both multiple and solitary OOCs may be related diseases within the entity of odontogenic cysts. Multiple OOCs are clinicopathologically and genetically distinct from OKC.
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Quistes Odontogénicos , Tumores Odontogénicos , Adolescente , Adulto , Femenino , Humanos , Inmunohistoquímica , Antígeno Ki-67 , Masculino , Quistes Odontogénicos/genética , Quistes Odontogénicos/patología , Tumores Odontogénicos/diagnóstico , Tumores Odontogénicos/genética , Receptor Patched-1/genética , Adulto JovenRESUMEN
High-dose-rate interstitial brachytherapy (HDR-ISBT) has recently come to be considered one of the most effective treatments for oral cancer. On the other hand, it is important to note that radiation therapy has some side effects. Especially, radiation-induced malignancy is probably the most serious complication affecting long-term survivors. We report a case of a radiation-induced undifferentiated spindle cell sarcoma that developed following HDR-ISBT for tongue squamous cell carcinoma (SCC). A 39-year-old woman with right tongue SCC underwent HDR-ISBT (60 Gy, 10 fractions, 8 days) treatment. Five years and one month later, a tumor had developed at the primary site. Surgery was performed for the tumor, which was histopathologically diagnosed as an undifferentiated spindle cell sarcoma. That was distinct from the squamous cell origin of the primary cancer. According to recently established criteria for radiation-induced malignancy, this case was classified as a radiation-induced sarcoma. A search of the literature revealed no previous report of radiation-induced malignancy following HDR-ISBT for tongue cancer.
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Anticuerpos Monoclonales Humanizados/efectos adversos , Antineoplásicos Inmunológicos/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/diagnóstico por imagen , Neumonía/inducido químicamente , Carcinoma de Pulmón de Células no Pequeñas/complicaciones , Glucocorticoides/uso terapéutico , Humanos , Enfermedades Pulmonares Intersticiales/inducido químicamente , Neoplasias Pulmonares/complicaciones , Factores de RiesgoRESUMEN
OBJECTIVE: Although class III beta-tubulin (TUBB3) is not expressed in normal epithelium, its expression in cancers of some organs has been reported. Herein, we investigated the expression pattern and expression levels of TUBB3 in oral squamous cell carcinoma (SCC), and assessed whether TUBB3 immunostaining could improve the diagnostic accuracy of oral scraping liquid-based cytology (LBC). METHODS: Paraffin sections of biopsies from 107 patients with primary SCC and 30 patients with squamous papilloma of the tongue or gingiva were immunostained for TUBB3. In addition, 15 LBC samples obtained from the study participants with SCC were immunostained for TUBB3. Seven LBC samples were false-negative. The TUBB3 expression level in each sample was evaluated and classified as 3+, 2+, 1+, or 0. RESULTS: TUBB3 expression was confirmed in 91.6% of paraffin-embedded SCC specimens. Clear and diffuse positivity (2+ or above) was observed in 77.6% of the total cases. In the well-differentiated type, tumour cells in the middle layer of the parenchyma specifically expressed TUBB3. In almost LBC samples, cancerous intermediate cells showed immunopositivity similar to that of paraffin samples, even if cellular atypia was not clear in Papanicolaou staining. CONCLUSIONS: TUBB3 immunostaining is useful for diagnosing oral SCC in scraping LBC, especially when samples consist of intermediate cells with little morphological change. Moreover, TUBB3 immunostaining could improve the diagnostic accuracy of oral scraping LBC by reducing false-negatives.
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Humanos , Neoplasias de la Boca/diagnóstico , Parafina , Carcinoma de Células Escamosas de Cabeza y Cuello , Tubulina (Proteína)/genéticaRESUMEN
Clear cell carcinoma (CCC) is a rare epithelial malignant tumor of the salivary glands. It is characterized by tumor cells with clear cytoplasm, hyalinized stroma, and most importantly the fusion genes EWSR1-ATF1, EWSR1-CREM, and EWSR1-PLAG1. Break-apart FISH has been performed for multiple CCC cases, but direct sequencing analysis has been performed in relatively few. Herein, we report an interesting case of CCC harboring three EWSR1-ATF1 translocations: EWSR1 exon 8-ATF1 exon 4, EWSR1 exon 7-ATF1 exon 4, and EWSR1 exon 7-ATF1 exon 5. This case indicates the possibility of independent EWSR1-ATF1 gene translocations, and could provide insight into CCC tumorgenesis.
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Adenocarcinoma de Células Claras , Proteínas de Fusión Oncogénica , Adenocarcinoma de Células Claras/genética , Exones , Humanos , Boca , Proteínas de Fusión Oncogénica/genética , Proteína EWS de Unión a ARN/genética , Factores de Transcripción/genéticaRESUMEN
Alveolar soft part sarcoma (ASPS) is a rare soft tissue sarcoma characterized by an alveolar or organoid arrangement of polygonal tumour cells separated by fibrovascular septa. A specific fusion gene [ASPS critical region 1 (ASPSCR1)-TFE3] was detected in ASPS. Despite being a slow-growing tumour without pain and dysfunction, ASPS is characterized by early metastasis, which leads to poor prognosis. Herein, we report a rare case of primary ASPS of the cheek harbouring ASPSCR1 (exon 7)-TFE3 (exon 5) fusion gene in a 21 year-old woman. This tumour was a well-circumscribed, smooth, round mass that was clinically suspected as a benign tumour. However, histologically, it was observed that the polygonal tumour cells were arranged in solid and alveolar growth patterns. Post-operative examination of the whole body excluded the possibility of metastasis at other sites. Thus, careful immunohistochemical and genetic analyses, as well as whole-body examination, demonstrated that the tumour was a primary ASPS of the cheek.
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Sarcoma de Parte Blanda Alveolar/diagnóstico , Mejilla , Medios de Contraste , Diagnóstico Diferencial , Femenino , Humanos , Metástasis Linfática , Imagen por Resonancia Magnética , Sarcoma de Parte Blanda Alveolar/secundario , Sarcoma de Parte Blanda Alveolar/cirugía , Adulto JovenRESUMEN
Clear cell carcinoma (CCC) is a rare low-grade malignant salivary gland carcinoma. EWSR1-ATF1 fusion has been characterized as a consistent finding in CCC, with breakpoints described between EWSR1 exon 11 and ATF1 exon 3. So far, over 100 cases of CCC harboring EWSR1 rearrangement arising from salivary gland of the oral cavity have been reported. Although EWSR1 involvement in these cases was confirmed by EWSR1 break-apart FISH indicating the translocation, sequence analysis for EWSR1-ATF1 fusion type has been reported only in three cases of CCC so far. Herein, we report a CCC case with novel EWSR1-ATF1 fusion (EWSR1 exon 15 and ATF1 exon 5) arising in minor salivary gland and review the role of the chimeric variants in some malignancies with EWSR1-ATF1 rearrangement. Current tumor was composed of the small nests of clear tumor cells and hyalized fibrous stroma. Immunohistochemically, the tumor was positive for AE1/AE3, CK5/6 and p63, negative for S100, Melan-A, SMA and CD10. After 8 months of follow-up, there are no evidence of recurrence.
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Adenocarcinoma de Células Claras/genética , Adenocarcinoma de Células Claras/patología , Proteínas de Fusión Oncogénica/genética , Neoplasias de las Glándulas Salivales/genética , Neoplasias de las Glándulas Salivales/patología , Femenino , Humanos , Persona de Mediana Edad , Hueso Paladar/patología , Glándulas Salivales Menores/patologíaRESUMEN
Fam20C, which phosphorylates many secretory proteins with S-x-E/pS motifs, is highly expressed in bone and tooth tissues, implying that Fam20C-mediated phosphorylation is critical for regulation of these mineralized tissues. Previous studies of Fam20C-deficient mice revealed that Fam20C plays important roles in bone formation and mineralization. However, Fam20C-deficient mice develop hypophosphatemia, a systemic factor that masks the local effect of Fam20C in the bone tissue; consequently, the local role of Fam20C remains unknown. To elucidate the local function of Fam20C in bone tissue, we studied osteoblast-specific Fam20C transgenic (Fam20C-Tg) mice, which have no alteration in serum calcium and phosphate levels. Fam20C-Tg mice had more highly phosphorylated proteins in bone tissue than wild-type mice. In cortical bone of Fam20C-Tg mice, bone volume, mineralization surface (MS/BS), and mineral apposition rate (MAR) were elevated; in addition, the transgenic mice had an elevated number of vascular canals, resulting in an increased cortical porosity. Osteocyte number was elevated in the transgenics, but osteoblast number was unchanged. The microstructure of bone matrix characterized by the preferential orientation of collagen and apatite, was degraded and thus the mechanical function of bone material was deteriorated. In trabecular bone of Fam20C-Tg mice, bone volume was reduced, whereas MS/BS and MAR were unchanged. Osteoclast number was elevated and eroded surface area was non-significantly elevated with an increased serum CTX-I level, whereas osteoblast number was unchanged. These findings indicated that Fam20C overexpression in osteoblasts promotes cortical bone formation by increasing MS/BS and MAR and promoting osteocyte differentiation, but does not affect trabecular bone formation. Furthermore, Fam20C overexpression indirectly promotes osteoclastic bone resorption in cortical and trabecular bones. Our findings show that osteoblastic Fam20C-mediated phosphorylation in bone tissue regulates bone formation and resorption, and bone material quality.
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Resorción Ósea , Osteogénesis , Animales , Densidad Ósea , Huesos/metabolismo , Proteínas de Unión al Calcio , Proteínas de la Matriz Extracelular/metabolismo , Ratones , Ratones Transgénicos , Osteoblastos/metabolismoRESUMEN
Dmp1 is an acidic phosphoprotein that is specifically expressed in osteocytes. During the secretory process, the full-length, precursor Dmp1 is cleaved into N- and C-terminal fragments. C-terminal Dmp1 is phosphorylated, becoming a highly negatively charged domain that may assist in bone mineralization by recruiting calcium ions and influencing subsequent mineral deposition. It has been recently reported that the Golgi-localized protein kinase Fam20C phosphorylates Dmp1 in vitro. To investigate this phosphorylation in situ, we determined the locations of phosphorylated Dmp1 and Fam20C in rat bones using immunohistochemistry. During osteocytogenesis, osteoblastic, osteoid, and young osteocytes (but not old osteocytes) express Dmp1 mRNA and contain Dmp1 protein in the Golgi apparatus. These Dmp1-producing cells were distributed across the surface layer of cortical bone. Using immunofluorescence, we found that N- and C-terminal Dmp1 fragments were predominantly distributed along the lacunar walls and canaliculi of mineralized bone, respectively, but were not present in the osteoid matrix. We also found that Fam20C and its substrate, C-terminal Dmp1, colocalized in the Golgi of osteoblastic, osteoid, and young osteocytes. Furthermore, phosphorylated C-terminal Dmp1 was present in the Golgi of young osteocytes. Double-labeling immunoelectron microscopy revealed that phosphorylated C-terminal Dmp1 localized to the canalicular wall in mineralized bone. These findings suggest that C-terminal Dmp1 is phosphorylated within osteocytes and then secreted into the pericanalicular matrix of mineralized bone. Phosphorylated, negatively charged C-terminal Dmp1 in the pericanalicular matrix may play an important role in bone mineralization by recruiting calcium ions.
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Huesos/metabolismo , Calcificación Fisiológica , Proteínas de la Matriz Extracelular/química , Proteínas de la Matriz Extracelular/metabolismo , Fosfoproteínas/química , Fosfoproteínas/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Animales , Inmunohistoquímica , Masculino , Fosforilación , Ratas , Ratas WistarRESUMEN
Cancer-initiating cells (CICs) are specialized cells that have the ability to self-renew and are multipotent. We recently demonstrated that Forkhead box O3a (FoxO3a)-expressing cells exhibited a CIC-like potential in Hodgkin's lymphoma (HL). A proportion of HL patients are infected with Epstein-Barr virus (EBV). EBV-encoded latent membrane protein (LMP) 1 downregulates FoxO3a, suggesting that FoxO3a expression may be abolished in EBV-positive HL. Inhibitors of DNA-binding (ID) proteins are highly conserved transcription factors mediating stem cell functions. To the best of our knowledge, no study has investigated possible associations among ID1, FoxO3a and LMP1 expression in HL to date. We immunohistochemically evaluated the expression of the three abovementioned factors in HL patients. The ID1 expression level was inversely correlated with that of FoxO3a (P=0.00035). LMP1-positive HL cells abundantly expressed ID1 (P=0.029), but not FoxO3a (P=0.00085). Thus, our previous observation that FoxO3a may serve as a marker of CICs may not be applicable in EBV-positive HL patients, but rather ID1 may be a candidate CIC marker in this type of HL.
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Cleavage of the antigenic telopeptide region from type I collagen yields atelocollagen, and this is widely used as a scaffold for bone regeneration combined with cells, growth factors, etc. However, neither the biological effect of atelocollagen alone or its contribution to bone regeneration has been well studied. We evaluated the chronological histological changes during bone regeneration following implantation of non-crosslinked atelocollagen (Koken Co., Ltd.) in rat calvarial defects. One week after implantation, osteogenic cells positive for runt-related transcription factor 2 (Runx2) and osteoclasts positive for tartrate-resistant acid phosphatase (TRAP) were present in the atelocollagen implant in the absence of bone formation. The number of Runx2-positive osteogenic cells and Osterix-positive osteoblasts increased 2 weeks after implantation, and bone matrix proteins (osteopontin, OPN; osteocalcin, OC; dentin matrix protein 1, DMP1) were distributed in newly formed bone in a way comparable to normal bone. Some resorption cavities containing osteoclasts were also present. By 3 weeks after implantation, most of the implanted atelocollagen was replaced by new bone containing many resorption cavities, and OPN, OC, and DMP1 were deposited in the residual collagenous matrix. After 4 weeks, nearly all of the atelocollagen implant was replaced with new bone including hematopoietic marrow. Immunohistochemistry for the telopeptide region of type I collagen (TeloCOL1) during these processes demonstrated that the TeloCOL1-negative atelocollagen implant was replaced by TeloCOL1-positive collagenous matrix and new bone, indicating that new bone was mostly composed of endogenous type I collagen. These findings suggest that the atelocollagen itself can support bone regeneration by promoting osteoblast differentiation and type I collagen production.
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Regeneración Ósea/efectos de los fármacos , Sustitutos de Huesos/uso terapéutico , Colágeno/uso terapéutico , Cráneo/anatomía & histología , Fosfatasa Ácida/metabolismo , Animales , Colágeno Tipo I/biosíntesis , Isoenzimas/metabolismo , Masculino , Osteogénesis , Ratas , Ratas Wistar , Fosfatasa Ácida TartratorresistenteRESUMEN
Dentin matrix protein (DMP1) is a non-collagenous bone matrix protein produced specifically by osteocytes. Because of its highly acidic nature, DMP1 can participate in bone matrix mineralization through Ca(2 + ) binding capacity. Inactivating mutations in DMP1 have recently been shown to cause autosomal recessive hypophosphatemic rickets (ARHR) . In a murine model of ARHR, DMP1-null mice had increased fibroblast growth factor23 (FGF23) expression in osteocytes, indicating that DMP1 participates in the systemic phosphate regulation by restraining osteocytic FGF23 production. In addition, the DMP1 promoter has been used frequently as an osteocyte-specific promoter. However, DMP1 is not expressed in all osteocytes. DMP1 expression is seen in osteoblastic-, osteoid-, young osteocytes of the superficial bone layer, but is reduced remarkably in old osteocytes distributed over the bone inside. This pattern of DMP1 expression may influence the interpretation of DMP1 function and the studies that use the DMP1 promoter.