Relevant proteins for the monitoring of engraftment phases after allogeneic hematopoietic stem cell transplantation.

INTRODUCTION: Hematopoietic Stem Cell Transplant (HSCT) has been successfully used as standard therapy for hematological disorders. After conditioning therapy, patients undergoing allogeneic HSCT, present three different phases of engraftment: early pre-engraftment, early post-engraftment, and late engraftment. Severe complications are associated with morbidity, mortality, and malignancies in these phases, which include effects on the oral cavity. OBJECTIVES: The changes in the salivary composition after HSCT may contribute to identifying relevant proteins that could map differences among the phases of diseases, driven for personalized diagnostics and therapy. METHODS: Unstimulated whole saliva was collected from patients submitted to HSCT. The samples were submitted to trypsin digestion for a Mass spectrometry analysis. MaxQuant processed the Data analysis, and the relevant expressed proteins were subjected to pathway and network analyses. RESULTS: Differences were observed in the most identified proteins, specifically in proteins involved with the regulation of body fluid levels and the mucosal immune response. The heatmap showed a list of proteins exclusively expressed during the different phases of HSCT: HBB, KNG1, HSPA, FGB, APOA1, PFN1, PRTN3, TMSB4X, YWHAZ, CAP1, ACTN1, CLU and ALDOA. Bioinformatics analysis implicated pathways involved in protein processing in the endoplasmic reticulum, complement and coagulation cascades, apoptosis signaling, and cholesterol metabolism. CONCLUSION: The compositional changes in saliva reflected the three phases of HSCT and demonstrated the usefulness of proteomics and computational approaches as a revolutionary field in diagnostic methods.

Relevant proteins for the monitoring of engraftment phases after allogeneic hematopoietic stem cell transplantation

Abstract Introduction Hematopoietic Stem Cell Transplant (HSCT) has been successfully used as standard therapy for hematological disorders. After conditioning therapy, patients undergoing allogeneic HSCT, present three different phases of engraftment: early pre-engraftment, early post-engraftment, and late engraftment. Severe complications are associated with morbidity, mortality, and malignancies in these phases, which include effects on the oral cavity. Objectives The changes in the salivary composition after HSCT may contribute to identifying relevant proteins that could map differences among the phases of diseases, driven for personalized diagnostics and therapy. Methods Unstimulated whole saliva was collected from patients submitted to HSCT. The samples were submitted to trypsin digestion for a Mass spectrometry analysis. MaxQuant processed the Data analysis, and the relevant expressed proteins were subjected to pathway and network analyses. Results Differences were observed in the most identified proteins, specifically in proteins involved with the regulation of body fluid levels and the mucosal immune response. The heatmap showed a list of proteins exclusively expressed during the different phases of HSCT: HBB, KNG1, HSPA, FGB, APOA1, PFN1, PRTN3, TMSB4X, YWHAZ, CAP1, ACTN1, CLU and ALDOA. Bioinformatics analysis implicated pathways involved in protein processing in the endoplasmic reticulum, complement and coagulation cascades, apoptosis signaling, and cholesterol metabolism. Conclusion The compositional changes in saliva reflected the three phases of HSCT and demonstrated the usefulness of proteomics and computational approaches as a revolutionary field in diagnostic methods.

Claudin expression is maintained in mucoepidermoid carcinoma of the salivary gland.

OBJECTIVE: The aim of the present study was to investigate the expression of claudin-1, -3, -4, -5 and -7 proteins in mucoepidermoid carcinoma of oral cavity and analyze whether EGF may interfere in the expression of the genes that encode claudins using in vitro models. MATERIAL AND METHODS: Using immunohistochemistry, the expression of claudins was searched in 36 histologically graded cases of mucoepidermoid carcinoma. The association of expression of claudins with clinical-pathological parameters was evaluated. An in vitro step investigated the influence of EGF on gene expression of claudins by real time RT-PCR technique. RESULTS: Claudin-1, -3, -4, -5, and -7 were highly expressed in most mucoepidermoid carcinomas. These expressions were compared with clinicopathological parameters. High expression of claudin-1 was associated with patients over 40 years-old (p = 0.05) and Caucasians (p = 0.024). In vitro experiments demonstrated a tendency for Claudin gene expression increase after EGF stimulus. CONCLUSIONS: The expression of claudins is maintained in mucoepidermoid carcinoma cells and EGF could be related with this expression. Our results point out to a fundamental biological importance to CLDNs in normal and neoplastic tissue. The expression patterns of CLDNs does not yet allow a clinical application, but the biological knowledge will ground evidence to new studies towards possible target-therapies.

A Rare Case of Concomitant Maxilla and Mandible Brown Tumours, Papillary Thyroid Carcinoma, Parathyroid Adenoma, and Osteitis Fibrosa Cystica.

Objective. The brown tumour of hyperparathyroidism is a result of a metabolic disorder caused by primary hyperparathyroidism. Report. We described a case of a 37-year-old female patient presenting bimaxillary intraoral lesions and swelling in the neck. Incisional biopsy of the oral lesion was performed and histopathological examination revealed a central giant cell lesion composed by intense haemorrhagic exudate, abundant presence of giant cells, and areas with hemosiderin pigment. The patient also presented high levels of serum calcium and parathyroid hormone, hyperfunctioning parathyroid tissue, bilateral parenchymal nephropathy, and densitometry lower than expected, showing an advanced stage of osteitis fibrosa cystica. Synchronous parathyroid adenoma and papillary thyroid carcinoma were confirmed by imaging exams and histopathologically. Conclusion. The composition of all the clinical, pathological, and imaging findings led to the final diagnosis of brown tumour of hyperparathyroidism. The occurrence of parathyroid adenoma, papillary thyroid carcinoma, and brown tumours of hyperparathyroidism in their late stage (osteitis fibrosa cystica) associated with oral brown tumours involving the mandible and maxilla is extremely rare.

An atrophic, telangiectatic patch at the distal border of the tongue: a mucous membrane manifestation of xeroderma pigmentosum.

Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder characterized by clinical and cellular sensitivity, pigmentary changes, and early development of malignancies in sun-exposed mucocutaneous and ocular structures due to a defective ability to repair intracellular DNA damage. Individuals with XP also have a greater frequency of oral cancer, particularly squamous cell carcinoma of the anterior third of the tongue. The current study reports four cases of XP that exhibited a characteristic crescent-shaped, atrophic, telangiectatic area on the distal border of the tongue and correlates this lesion with the development of tumors at this site during follow-up. The tongue lesion was photographed and biopsied in the four patients. During routine follow-up visits, new biopsies were performed if additional tongue lesions were observed. The studied lesions were similar in the four patients. During follow-up, squamous cell carcinoma developed in one patient and pyogenic granuloma developed in three patients and was relapsing in one. The lesion remained stable in one patient during the study. The atrophic and telangiectatic patches probably occur because of chronic sun damage to the exposed portion of the tongue, and this area has a high predisposition for the development of benign and malignant tumors.

Adhesion molecules in primary oral mucosal melanoma: study of claudins, integrins and immunoglobulins in a series of 35 cases.

Primary oral mucosal melanoma is a rare aggressive tumor. Recent studies have demonstrated a correlation between increased tumor invasion and the metastatic phenotype and altered adhesion molecule expression profiles. The present study analyzed the expression of integrins, claudins, and immunoglobulin-like adhesion molecules in oral mucosal melanomas and correlated results with clinical parameters. Immunohistochemical analyses of the expression patterns of these molecules were performed on thirty-five cases of primary oral mucosal melanomas organized in a tissue microarray. The results were correlated with clinical and histological features of the cohort. A number of integrin subunits were negative and this was related with vascular invasion. Positivity of integrin beta-3 and CD166 (activated leukocyte cell adhesion molecule) was statistically associated with extensive vascular invasion (P < 0.05). Lower expression of CD54 (intercellular cell adhesion molecule) was associated with cases with extensive necrosis. Most cases with metastatic disease were negative for CD66 (carcinoembryonic antigen-related cell adhesion molecule). Several subunits of claudins were negative and, although not statistically significant, this lack of expression was partially associated with histological factors of poor prognosis. Altered patterns of adhesion molecule expression, mainly integrins and immunoglobulin-like proteins, may participate in the pathogenesis and outcome of oral mucosal melanomas.

Facial lesions caused by renal osteodystrophy in a patient with chronic renal insufficiency: a case report / Lesões faciais por osteodistrofia renal em paciente com insuficiência renal crônica: relato de caso

PURPOSE: Chronic renal insufficiency (CRI) is the last stage of a chronic renal condition in which the kidney loses its filtration and endocrine functions. Chronic endocrine hypofunction causes generalized damage to the body known as Uremic Syndrome, which affects the central nervous system as well as the cardiovascular, hematologic, dermatologic, ophthalmic, endocrine, respiratory, gastrointestinal and skeletal systems. The present study reports the case of a female patient with CRI who presented facial osteodystrophy of the osteitis fibrosa type, and highlights the main features of this condition. CASE DESCRIPTION: A 24-year old, female, Caucasian patient presented chronic glomerulonephritis recurrence and lost the transplanted kidney five years before, undergoing arteriovenous fistula hemodialysis three times a week. She presented swelling of the left masseter area with a hard consistency on palpation, covered by intact skin, swelling at the bottom of the left atrium, with a hard consistency on palpation, a mucosa-like color and absence of inflammation signs, suggesting expansive bone lesions on the face. These features were compatible with hyperparathyroidism brown tumor and/or osteodystrophy. The CT scan showed expansive bone lesions of heterogeneous appearance on the left jaw, maxilla/nasal floor, and right frontotemporal suture areas. The clinical and histopathological characteristics of the lesion, in association with PHT hormone high serum levels led to renal osteodystrophy diagnosis. The patient was referred to the nephrology services. CONCLUSION: Osteodystrophic bone alterations have a high prevalence in renal disease patients, and the dentist must take these alterations into consideration in bone lesion diagnosis for this specific group of patients.

OBJETIVO: A Insuficiência Renal Crônica (IRC) é o último estágio da doença renal crônica, na qual o rim perde sua função de filtração e endócrina. A hipofunção endócrina renal ocasiona danos generalizados ao organismo, que no conjunto são conhecidos como Síndrome Urêmica, sendo composta por danos que comprometem o sistema nervoso central, assim como os sistemas cardiovasculares, hematológicos, dermatológicos, oftálmicos, endócrinos, respiratórios, gastrointestinais e ósseos. O presente estudo irá relatar o caso de uma paciente portadora de IRC apresentando osteodistrofia em face do tipo osteíte fibrosa, evidenciando as principais características dessa doença. DESCRIÇÃO DO CASO: Uma paciente de 24 anos, sexo feminino, caucasiana, apresentou glomerulonefrite recorrente após perda do rim transplantado, estando sob hemodiálise três vezes por semana. Apresentou inchaço da área do m. masseter esquerdo com consistência dura à palpação, coberto por pelo de aspecto normal, inchaço do átrio esquerdo, com consistência dura e ausência de sinais inflamatórios, sugerindo lesões ósseas na face. Estas características eram compatíveis com tumor marrom de hiperparatireoidismo e/ou osteodistrofia. A imagem de tomografia computadorizada mostrou lesões ósseas expansivas de aparência heterogênea na mandíbula esquerda, assoalho da maxila e nasal, e nas áreas de sutura frontotemporal direita. As características clínicas e histopatológicas da lesão, em associação com níveis séricos elevados de hormônio PHT conduziram ao diagnóstico de osteodistrofia renal. A paciente foi encaminhada para o serviço de nefrologia. CONCLUSÃO: As alterações ósseas osteodistróficas são de grande prevalência em pessoas com doença renal, tendo o cirurgião-dentista o dever de levá-las em consideração no diagnóstico de lesões ósseas neste grupo específico de pessoas.

Oral mucosal melanoma of the mandibular gingiva: a case report.

Oral mucosal melanoma is rare and is reported to be more aggressive than cutaneous melanoma. The incidence of oral mucosal melanoma peaks at 41 to 60 years of age and the male to female ratio is 2 to 1. Preferred sites in the oral mucosa include the hard palate and maxillary alveolar crests. Risk factors have not been clearly identified, but melanotic pigmentation is present in one-third of patients prior to the diagnosis of melanoma. We report an unusual case of oral mucosal melanoma of the mandibular gingiva with the main characteristics of an in situ lesion and areas of superficial invasion in a 45-year-old woman. The patient was treated with surgical resection of the lesion and a 54-month follow-up shows no evidence of recurrence. Oral mucosal melanomas are aggressive neoplasms that may arise from prior pigmented lesions in the oral mucosa. Classification of these tumors is not well-established and the main prognostic factor appears to be lymph node compromise. The main treatment modality is surgical resection.

Lichen planus sialadenitis: a mucosal analog of lichen planopilaris and lichen planoporitis.

Lichen planus (LP) is the most prevalent dermatological disorder with oral manifestation. Oral lesions comprise a broad spectrum of clinical presentations. We report the case of a 56-year-old woman who presented erosive LP on the buccal and lower lip mucosae. Besides typical erosions, small white keratotic papules on an erythematosus background on the lower lip mucosa were observed. Biopsy of lower lip lesions showed an unusual histopathological presentation consisting of a lichenoid inflammation targeted to salivary gland ducts. This is probably a salivary gland analog of lichen planopilaris and lichen planoporitis.

Primary oral mucosal melanoma: a series of 35 new cases from South America.

Oral mucosal melanoma is rare and reported to be more aggressive than its cutaneous counterpart. Due to the rarity of this entity, data on epidemiology, tumor behavior, treatment, follow-up, and survival of patients are mainly based on single case reports. The few existing series of patients show that oral mucosa melanoma has its peak between 41 and 60 years of age, and male to female ratio is 2:1. Preferred oral sites include hard palate and maxillary alveolar crests. Risk factors have not been clearly identified, and surgical treatment is still the treatment of choice for oral mucosal melanomas. The authors retrospectively studied 35 patients with primary melanoma of the oral cavity to report their clinical and pathological features, such as age, sex, site of the tumor, metastasis, treatment, response to therapy, and outcome. We found no significant sex predominance, and the mean age of the patients was 60.6 years, with a range from 9 to 91 years. The majority of the patients (71.42%) had palate commitment, and invasive histopathological aspect was observed in 80% of the specimens (grade 3). Long-distance metastasis was found in 60% of the cases. Fourteen patients were submitted to wide surgical resections, with local relapse being observed in 11 of them (78.5%). The authors suggest that improved outcome in oral malignant melanoma requires the development of new therapies and the prevention of distant metastasis.