Valoración del papel de la angiogénesis y de las moléculas que regulan las vías de señalización de la osteoclastogénesis en el mixoma odontogénico

184 p.Los tumores odontogénicos (TO) representan un grupo de neoplasiasderivadas de elementos odontogénicos epiteliales, ectomesenquimatosos y/omesenquimatosos que constituyen un conjunto heterogéneo de lesiones,localizadas exclusivamente en la región maxilofacial y presentan diversascaracterísticas histopatológicas y manifestaciones clínicas.Debido a la gran diversidad de lesiones que pueden formarse a partir de lostejidos odontogénicos, se han publicado diferentes esquemas de clasificación, enun intento de definir sus criterios diagnósticos y su comportamiento biológico.En todas las clasificaciones, el mixoma odontogénico (MO) aparece comouna neoplasia benigna de estirpe mesenquimatosa, cuyas características, aunquebien definidas, son similares a las de otras entidades benignas localmenteagresivas.El Mixoma Odontogénico (MO) es una neoplasia benigna intraóseaespecífica de los huesos maxilares, que muestra un comportamiento localmenteagresivo y una elevada capacidad recidivante. Su incidencia varía entre el 2,2% yel 17,7% de todos los tumores odontogénicos. Aparece principalmente enindividuos jóvenes, durante la segunda y tercera décadas, en un rango de edadque va desde los 5 a los 72 años, con predilección por las mujeres en relación de2 a 1. La localización más común es la mandíbula, con 2/3 de los casos y muestraun crecimiento lento, progresivo y generalmente asintomático. Posee un granpotencial de infiltración y destrucción ósea y una elevada capacidad derecurrencia.Al realizar el análisis inmunohistoquímico de la expresión de las proteínasMMP-2, MMP-9, Bcl-2, CD-105, Triptasa, RANK, RANK-L y OPG en los MOs, nosproporcionó datos importantes sobre el comportamiento biológico de estaneoplasia benigna localmente agresiva.Los mixomas odontogénicos muestran una expresión significativamentemayor de la metaloproteinasa de matriz-9, que los folículos dentarios. Se reconoceuna asociación significativamente mayor de la proteína RANK con OPG en losmixomas odontogénicos, y entre las proteínas RANK y RANK-L en los folículosdentarios lo que estaría relacionado con las características clínicas de estaneoplasia

Assessment of CD-105 as an angiogenic modulator in odontogenic myxomas and dental follicles

Aim. Odontogenic myxoma is a benign intraosseous neoplasm of the jaws, with a locally aggressive behavior and a high recurrence rate. CD-105 is a homodimeric cell membrane glycoprotein and is a component of the TGF-β1 growth factor receptor complex that modulates angiogenesis by regulating the proliferation, differentiation and cellular migration. The aim of this study is to quantify the microvascular density of the odontogenic myxoma based on the expression of CD-105. Materials and Methods. The analysis included 18 odontogenic myxoma and 18 dental follicles as controls. A standard immunohistochemical procedure was performed with the CD-105 antibody. Five representative fields (40×) of the odontogenic myxoma and the dental follicles were selected to determine the microvascular density, which was then followed by a descriptive and comparative statistical analysis. Results. Dental follicles presented a significantly higher microvascular density compared with odontogenic myxoma (P = .001). The odontogenic myxoma smaller than 3 cm showed a greater microvascular density than those larger than 3 cm in size (P > .05), and the microvascular density was lower in large odontogenic myxomas as compared with the dental follicles (P = .003). Conclusion. A weaker expression of CD-105 in odontogenic myxoma might indicate a lower angiogenic activity, suggesting that vascular proliferation has a limited role in the growth mechanisms and in the aggressive behavior of this neoplasm.Aim. Odontogenic myxoma is a benign intraosseous neoplasm of the jaws, with a locally aggressive behavior and a high recurrence rate. CD-105 is a homodimeric cell membrane glycoprotein and is a component of the TGF-β1 growth factor receptor complex that modulates angiogenesis by regulating the proliferation, differentiation and cellular migration. The aim of this study is to quantify the microvascular density of the odontogenic myxoma based on the expression of CD-105. Materials and Methods. The analysis included 18 odontogenic myxoma and 18 dental follicles as controls. A standard immunohistochemical procedure was performed with the CD-105 antibody. Five representative fields (40×) of the odontogenic myxoma and the dental follicles were selected to determine the microvascular density, which was then followed by a descriptive and comparative statistical analysis. Results. Dental follicles presented a significantly higher microvascular density compared with odontogenic myxoma (P = .001). The odontogenic myxoma smaller than 3 cm showed a greater microvascular density than those larger than 3 cm in size (P > .05), and the microvascular density was lower in large odontogenic myxomas as compared with the dental follicles (P = .003). Conclusion. A weaker expression of CD-105 in odontogenic myxoma might indicate a lower angiogenic activity, suggesting that vascular proliferation has a limited role in the growth mechanisms and in the aggressive behavior of this neoplasm

Fibroma osificante juvenil psamomatoide maxilar con quiste óseo aneurismático secundario. Reporte de un caso

El fibroma osificante juvenil psamomatoide es un tumor raro y de crecimiento progresivo de los huesos extragnáticos craneofaciales, con tendencia a un comportamiento agresivo localmente y a la recidiva. La característica patognomónica es la presencia de osificaciones esféricas parecidas a los cuerpos de psamoma. Se han reportado algunos casos asociados a quiste óseo aneurismático secundario. El tratamiento quirúrgico radical y el seguimiento clínico y radiográfico estricto parecen ser el abordaje de preferencia para estas lesiones. Se reporta un caso de un fibroma osificante juvenil psamomatoide maxilar, asociado a quiste óseo aneurismático, en una paciente de 10 años de edad.The juvenile psammomatoid ossifying fibroma is a rare, progressive growing tumor of the extragnathic craniofacial bones, with tendency to an agressive behavior and recurrence. The pathognomonic histopathologic feature is the presence of spherical ossicles resembling to psammoma bodies. Some cases in association with a secondary aneurysmal bone cyst have been reported. The radical surgical treatment with a clinical and imaging follow-up appears to be the preferred approach for this lesions. We report a case of psammomatoid juvenile ossifying fibroma in the maxilla in association to secondary aneurysmal bone cyst in a 10-year-old female patient

Validation of COL11A1/procollagen 11A1 expression in TGF-β1-activated immortalised human mesenchymal cells and in stromal cells of human colon adenocarcinoma

Our observations stress once more the usefulness of the DMTX1/1E8.33 mAb for cancer research, and the clinical significance of procollagen 11A1 as a very valuable biomarker to characterise cancer-associated stromal cells and to evaluate human colon adenocarcinomas.Background: The human COL11A1 gene has been shown to be up-regulated in stromal cells of colorectal tumours, but, so far, the immunodetection of procollagen 11A1, the primary protein product of COL11A1, has not been studied in detail in human colon adenocarcinomas. Some cancer-associated stromal cells seem to be derived from bone marrow mesenchymal cells; the expression of the COL11A1 gene and the parallel immunodetection of procollagen 11A1 have not been evaluated in these latter cells, either. Methods: We used quantitative RT-PCR and/or immunocytochemistry to study the expression of DES/desmin, VIM/vimentin, ACTA2/αSMA (alpha smooth muscle actin) and COL11A1/procollagen 11A1 in HCT 116 human colorectal adenocarcinoma cells, in immortalised human bone marrow mesenchymal cells and in human colon adenocarcinoma-derived cultured stromal cells. The immunodetection of procollagen 11A1 was performed with the new recently described DMTX1/1E8.33 mouse monoclonal antibody. Human colon adenocarcinomas and non-malignant colon tissues were evaluated by immunohistochemistry as well. Statistical associations were sought between anti-procollagen 11A1 immunoscoring and patient clinicopathological features. Results: Procollagen 11A1 was immunodetected in human bone marrow mesenchymal cells and in human colon adenocarcinoma-associated spindle-shaped stromal cells but not in colon epithelial or stromal cells of the normal colon. This immunodetection paralleled, in both kinds of cells, that of the other mesenchymalrelated biomarkers studied: vimentin and alpha smooth muscle actin, but not desmin. Thus, procollagen 11A1+ adenocarcinoma-associated stromal cells are similar to “activated myofibroblasts”. In the series of human colon adenocarcinomas here studied, a high procollagen 11A1 expression was associated with nodal involvement (p = 0.05), the development of distant metastases (p = 0.017), and advanced Dukes stages (p = 0.047). Conclusion: The immunodetection of procollagen 11A1 in cancer-associated stromal cells could be a useful biomarker for human colon adenocarcinoma characterisation. Keywords: Procollagen 11A1, Human bone marrow mesenchymal cells, Cancer-associated stromal cells, Human colon adenocarcinom

COL11A1/(pro)collagen 11A1 expression is a remarkable biomarker of human invasive carcinoma-associated stromal cells and carcinoma progression

The COL11A1 human gene codes for the α1 chain of procollagen 11A1 and mature collagen 11A1, an extracellular minor fibrillar collagen. Under regular conditions, this gene and its derived products are mainly expressed by chondrocytes and mesenchymal stem cells as well as osteoblasts. Normal epithelial cells and quiescent fibroblasts from diverse locations do not express them. Mesenchyme-derived tumors and related conditions, such as scleroderma and keloids, are positive for COL11A1/(pro)collagen 11A1 expression, as well as high-grade human gliomas/glioblastomas. This expression is almost absent in benign pathological processes such as breast hyperplasia, sclerosing adenosis, idiopathic pulmonary fibrosis, cirrhosis, pancreatitis, diverticulitis, and inflammatory bowel disease. By contrast, COL11A1/(pro)collagen 11A1 is highly expressed by activated stromal cells of the desmoplastic reaction of different human invasive carcinomas, and this expression is correlated with carcinoma aggressiveness and progression, and lymph node metastasis. COL11A1 upregulation has been shown to be associated to TGF-β1, Wnt, and Hh signaling pathways, which are especially active in cancerassociated stromal cells. At the front of invasive carcinomas, neoplastic epithelial cells, putatively undergoing epithelial-to-mesenchymal transition, and carcinoma-derived cells with highly metastatic capabilities, can express COL11A1. Thus, in established metastases, the expression of COL11A1/ (pro)collagen 11A1 could rely on both the metastatic epithelial cells and/or the accompanying activated stromal cells. COL11A1/(pro)collagen 11A1 expression is a remarkable biomarker of human carcinoma-associated stromal cells and carcinoma progression

Importancia del diagnóstico precoz en el carcinoma mucoepidermoide. Relato de caso clínico

Mucoepidermoid carcinoma is the most frequent malignant tumor of the minor salivary glands, usually located in the palate. The objective of this case report is to demonstrate in the Paraguayan scientific literature the importance of early diagnosis of oral carcinomas as well as the fundamental role of the general dentist in identifying, guiding and referring the patient to the corresponding specialist. The clinical case presented is about a male patient who attended the Faculty of Dentistry of the National University of Asuncion. His dentist referred him after noticing a small but perceptible change in the normal coloration of the mucosa and occasional discomfort in the area of the hard palate. In the intraoral examination, an ovoid nodular lesion, purplish in color, 1cm in diameter, depressible on palpation, observed on the hard palate at the level of the premolars in the left hemiarch. An incisional biopsy performed for histopathological study, reporting a mucoepidermoid carcinoma. Regarding the early diagnosis of this type of pathology, the challenge for the general dentist will continues to be his continuous training in order to be able to successfully guide the patient in seeking care from the right specialist in case of any change in the oral cavity.El carcinoma mucoepidermoide es el tumor maligno más frecuente de las glándulas salivales menores localizándose por lo general en el paladar. El objetivo del presente reporte de caso es evidenciar en la literatura científica la importancia del diagnóstico precoz de carcinomas orales, así como, el rol fundamental que cumple el odontólogo general para identificar, guiar y derivar al paciente a un especialista. Se presenta el caso clínico de un paciente de sexo masculino que acudió a la Facultad de Odontología de la Universidad Nacional de Asunción, quien fue derivado por su odontóloga tras percibir un pequeño pero perceptible cambio en la coloración normal de la mucosa y molestias ocasionales en la zona del paladar duro. Al examen intraoral se observó en el paladar duro, a la altura de los premolares en la hemiarcada izquierda, una lesión nodular ovoidea, color violáceo, de 1cm de diámetro, depresible a la palpación. Se realizó una biopsia incisional para su estudio histopatológico, reportando un carcinoma mucoepidermoide. El diagnóstico precoz de este tipo de patologías es un desafío para el odontólogo general, quien debe orientar al paciente, ante cualquier cambio de la estructura normal de la cavidad bucal, para que acuda a un especialista

Oral Manifestations of COVID-19 in Paraguay: Results from an Online Survey.

Introducción: Estudios previos han reportado que pacientes infectados con el  virus del COVID-19, podrían manifestar sintomatologías a nivel de la cavidad oral. Objetivo: Evaluar la frecuencia de manifestaciones orales asociadas a COVID-19 en un segmento de la población paraguaya y determinar cuáles son las más prevalentes. Metodología: Estudio descriptivo de corte transversal. Fue realizada una encuesta electrónica de enero a marzo del 2022. Los datos fueron presentados como frecuencias y porcentajes y analizados mediante la prueba de chi-cuadrado. El análisis estadístico se realizó con el software R versión 4.0.3. Resultados: La muestra estuvo compuesta por 478 personas. El 79,50 % correspondió al sexo femenino y el 45,19 % tenía entre 25 y 34 años. El 65,48 % informó haber experimentado al menos 1 síntoma o signo oral durante el curso de COVID-19. La pérdida de la sensación de sabores amargos, seguida de la alteración del sabor de los alimentos y la pérdida de la percepción dulce, fueron los síntomas más comunes. Se encontró una proporción significativamente mayor de manifestaciones orales en el rango de 18-24 años (?²; p= 0,003). Entre las personas que desarrollaron COVID-19 de forma moderada a severa hubo mayor número de manifestaciones de síntomas orales (?²; p= 0,044). Discusión: Se identificó una alta frecuencia de manifestaciones orales en pacientes con casos de moderados a severos de COVID-19, destacándose los trastornos del gusto como los más predominantes. Los individuos más jóvenes fueron los más afectados.Introduction: Previous studies have reported that patients infected with the COVID-19 virus could manifest symptoms in the oral cavity. Objective: To evaluate the frequency of oral manifestations associated with COVID-19 in a segment of the Paraguayan population and determine the most prevalent ones. Methods: Descriptive cross-sectional study. An electronic survey was conducted from January to March 2022. The data were presented as frequencies and percentages and analyzed using the chi-square test. Statistical analysis was performed with R software version 4.0.3. Results: The sample consisted of 478 individuals. 79.50% were female, and 45.19% were between 25 and 34 years old. 65.48% reported having experienced at least 1 oral symptom or sign during the course of COVID-19. The loss of the sensation of bitter tastes, followed by the alteration of the taste of foods and the loss of sweetness perception, were the most common symptoms. A significantly higher proportion of oral manifestations was found in the 18-24 age range (?²; p= 0.003). Among people who developed COVID-19 in a moderate to severe form, a greater number of oral symptom manifestations were observed (?²; p= 0.044). Discussion: A high frequency of oral manifestations was identified in patients with moderate to severe cases of COVID-19, with taste disorders standing out as the most predominant. Younger individuals were the most affected

Overexpression of proCOL11A1 as a stromal marker of breast cancer

Background: Our previous studies demonstrated the expression of procollagen11A1 in fibroblasts of pancreatic cancer desmoplasia and the lack of expression in fibroblasts of pancreatitis by means of the polyclonal antibody (anti-proCOL11A1 pAb) we generated. In a similar way, we decided to compare the expression of procollagen11A1 in fibroblasts of infiltrating ductal carcinoma of the breast and fibroblasts of benign sclerosing lesions of the breast, in order to validate the anti-proCOL11A1 pAb in this setting and to study how proCOL11A1 expression relates to other prognostic and predictive factors, as well as to survival. Methods: 45 core biopsies of sclerosing adenosis and 50 core biopsies of infiltrating ductal carcinoma of the breast were stained with anti-proCOL11A1 pAb, a polyclonal antibody highly specific to the less homologous fraction of proCOL11A1 (in comparison with proCOL5A1 and proCOL11A2). In addition, the expression of the proCOL11A1 gene was measured by RT-qPCR. On the other hand, the expression of proCOL11A1 was compared to the expression of estrogenic receptors, progestagen receptors, the state of the epidermal growth factor receptor 2 (HER2), the histologic grade and the stage of the disease. We also compared the immunohistochemical expression of proCol11A1 to the disease-free interval, and to overall survival. Results: The immunohistochemical analysis showed that proCOL11A1 was expressed in 100% of infiltrating ductal carcinomas, but only focally expressed in 2.2% (1 case) of sclerosing adenosis, in agreement with RT-qPCR results. ProCOL11A1 expression did not prove to have a prognostic value in relation to the disease-free interval or to overall survival in infiltrating ductal carcinoma. Conclusion: The anti-proCOL11A1 pAb is a stromal marker for breast cancer and the expression of proCOL11A1 does not seem to have a prognostic value in infiltrating ductal carcinoma of the breast

Subcutaneous anti-COVID-19 hyperimmune immunoglobulin for prevention of disease in asymptomatic individuals with SARS-CoV-2 infection : a double-blind, placebo-controlled, randomised clinical trial

Anti-COVID-19 hyperimmune immunoglobulin (hIG) can provide standardized and controlled antibody content. Data from controlled clinical trials using hIG for the prevention or treatment of COVID-19 outpatients have not been reported. We assessed the safety and efficacy of subcutaneous anti-COVID-19 hyperimmune immunoglobulin 20% (C19-IG20%) compared to placebo in preventing development of symptomatic COVID-19 in asymptomatic individuals with SARS-CoV-2 infection. We did a multicentre, randomized, double-blind, placebo-controlled trial, in asymptomatic unvaccinated adults (≥18 years of age) with confirmed SARS-CoV-2 infection within 5 days between April 28 and December 27, 2021. Participants were randomly assigned (1:1:1) to receive a blinded subcutaneous infusion of 10 mL with 1 g or 2 g of C19-IG20%, or an equivalent volume of saline as placebo. The primary endpoint was the proportion of participants who remained asymptomatic through day 14 after infusion. Secondary endpoints included the proportion of individuals who required oxygen supplementation, any medically attended visit, hospitalisation, or ICU, and viral load reduction and viral clearance in nasopharyngeal swabs. Safety was assessed as the proportion of patients with adverse events. The trial was terminated early due to a lack of potential benefit in the target population in a planned interim analysis conducted in December 2021. registry: . 461 individuals (mean age 39.6 years [SD 12.8]) were randomized and received the intervention within a mean of 3.1 (SD 1.27) days from a positive SARS-CoV-2 test. In the prespecified modified intention-to-treat analysis that included only participants who received a subcutaneous infusion, the primary outcome occurred in 59.9% (91/152) of participants receiving 1 g C19-IG20%, 64.7% (99/153) receiving 2 g, and 63.5% (99/156) receiving placebo (difference in proportions 1 g C19-IG20% vs. placebo, −3.6%; 95% CI -14.6% to 7.3%, p = 0.53; 2 g C19-IG20% vs placebo, 1.1%; −9.6% to 11.9%, p = 0.85). None of the secondary clinical efficacy endpoints or virological endpoints were significantly different between study groups. Adverse event rate was similar between groups, and no severe or life-threatening adverse events related to investigational product infusion were reported. Our findings suggested that administration of subcutaneous human hyperimmune immunoglobulin C19-IG20% to asymptomatic individuals with SARS-CoV-2 infection was safe but did not prevent development of symptomatic COVID-19.

IL-6 serum levels predict severity and response to tocilizumab in COVID-19: An observational study

Background: Patients with coronavirus disaese 2019 (COVID-19) can develop a cytokine release syndrome that eventually leads to acute respiratory distress syndrome requiring invasive mechanical ventilation (IMV). Because IL-6 is a relevant cytokine in acute respiratory distress syndrome, the blockade of its receptor with tocilizumab (TCZ) could reduce mortality and/or morbidity in severe COVID-19. Objective: We sought to determine whether baseline IL-6 serum levels can predict the need for IMV and the response to TCZ. Methods: A retrospective observational study was performed in hospitalized patients diagnosed with COVID-19. Clinical information and laboratory findings, including IL-6 levels, were collected approximately 3 and 9 days after admission to be matched with preadministration and postadministration of TCZ. Multivariable logistic and linear regressions and survival analysis were performed depending on outcomes: need for IMV, evolution of arterial oxygen tension/fraction of inspired oxygen ratio, or mortality. Results: One hundred forty-six patients were studied, predominantly males (66%); median age was 63 years. Forty-four patients (30%) required IMV, and 58 patients (40%) received treatment with TCZ. IL-6 levels greater than 30 pg/mL was the best predictor for IMV (odds ratio, 7.1; P < .001). Early administration of TCZ was associated with improvement in oxygenation (arterial oxygen tension/fraction of inspired oxygen ratio) in patients with high IL-6 (P = .048). Patients with high IL-6 not treated with TCZ showed high mortality (hazard ratio, 4.6; P = .003), as well as those with low IL-6 treated with TCZ (hazard ratio, 3.6; P = .016). No relevant serious adverse events were observed in TCZ-treated patients. Conclusions: Baseline IL-6 greater than 30 pg/mL predicts IMV requirement in patients with COVID-19 and contributes to establish an adequate indication for TCZ administrationThis study was funded by Spanish Ministry of Economy, Industry and Competitiveness (MINECO) and Instituto de Salud Carlos III (grant nos. RD16/0011/0012 and PI18/ 0371 to I.G.A., grant no. PI19/00549 to A.A., and grant no. SAF2017-82886-R to F.S.-M.) and co-funded by the European Regional Development Fund. The study was also funded by ‘‘La Caixa Banking Foundation’’ (grant no. HR17-00016 to F.S.-M.) and ‘‘Fondos Supera COVID19’’ by Banco de Santander and CRUE. None of these sponsors have had any role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publicatio