PI3K/AKT/mTOR pathway activation in actinic cheilitis and lip squamous cell carcinomas

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Fibrosarcoma Originating In The Mandible

Fibrosarcoma is a malignant mesenchymal neoplasm of fibroblasts that rarely affects the oral cavity and can cause local recurrences or metastasis. In this article we describe a case of primary fibrosarcoma in the mandible in a 16-year-old girl. Microscopically the tumor showed an intense proliferation of spindle-shaped cells, varying little in size and shape and arranged in parallel bands, partly crossing each other, the mitotic activity was increased and there was nuclear pleomorphism. Immunohistochemically the cells only showed immunoreactivity for vimentin and negativity for S-100 protein, CD 68, cytokeratin cocktail, HMB-45, CD34, pan actin HHF 35, desmin, smooth muscle actin and epithelial membrane antigen (EMA). Based on clinical, radiological, histological and immunohistochemical findings the final diagnosis was high-grade intra-osseous fibrosarcoma. The treatment choice was radical surgery with mandibular reconstruction. After one year and nine months of the treatment the patient displayed multiple metastases. Radiation therapy and chemotherapy were used as adjuvant treatment. Unfortunately, the girl died two years after the initial diagnosis. © Medicina Oral S. L. C.I.F. B 96689336.113191194Lo Muzio, L., Mignogna, M.D., Pannone, G., Staibano, S., Testa, N.F., A rare case of fibrosarcoma of the jaws in a 4-year-old male (1998) Oral Oncol, 34, pp. 383-386Richardson, J.F., Fine, M.A., Goldman, H.M., Fibrosarcoma of the mandible: A clinicopathologic controversy: Report of a case (1972) J Oral Surg, 30, pp. 664-668Mark, R.J., Sercarz, J.A., Tran, L., Selch, M., Calcaterra, T.C., Fibrosarcoma of the Head and Neck. The UCLA experience (1991) Arch Otolaryngol Head Neck Surg, 117, pp. 396-401McKenna, W.G., Barnes, M.M., Kinsella, T.J., Rosenberg, S.A., Lack, E.E., Glatstein, E., Combined modality treatment of adult soft tissue sarcomas of the head and neck (1987) Int J Radiat Oncol Biol Phys, 13, pp. 1127-1133Van Blarcom, C.W., Masson, J.K., Dahlin, D.C., Fibrosarcoma of the mandible. A clinicopathologic study (1971) Oral Surg Oral Med Oral Pathol, 32, pp. 428-439Sadoff, R.S., Rubin, M.M., Fibrosarcoma of the mandible: A case report (1990) J Am Dent Assoc, 121, pp. 247-248Handlers, J.P., Abrams, A.M., Melrose, R.J., Milder, J., Fibrosarcoma of the mandible presenting as a periodontal problem (1985) J Oral Pathol, 14, pp. 351-356Pereira, C.M., Jorge Junior, J., Di Hipólito, O., Kowalski, L.P., Lopes, M.A., Primary intraosseous fibrosarcoma of jaw (2005) Int J Oral Maxillofac Surg, 34, pp. 579-581Antonescu, C.R., Erlandson, R.A., Huvos, A.G., Primary fibrosarcoma and malignant fibrous histiocytoma of bone - A comparitive ultrastructural study: Ecidence of a spectrum of fibroblastic differentiation (2000) Ultrastruct Pathol, 24, pp. 83-91Mosqueda-Taylor, A., Meneses-García, A., Ruíz-Godoyrivera Lm Suárez-Roa, M.I., Luna-Ortiz, K., Malignant odontogenic tumors. A retrospective and collaborative study of seven cases (2003) Med Oral, 8, pp. 110-121Huguet, P., Castellvi, J., Avila, M., Alejo, M., Autonell, F., Basas, C., Ameloblastic fibrosarcoma: Report of a case. Immunohistochemical study and review of the literature (2001) Med Oral, 6, pp. 173-179Yamaguchi, S., Nagasawa, H., Suzuki, T., Fujii, E., Iwaki, H., Takagi, M., Sarcomas of the oral and maxillofacial region: A review of 32 cases in 25 years (2004) Clin Oral Invest, 8, pp. 52-55Lukinmaa, P.L., Hietanen, J., Swan, H., Ylipaavalniemi, P., Perkki, K., Maxillary fibrosarcoma with extracellular immuno-characterization (1988) Br J Oral Maxillofac Surg, 26, pp. 36-4

Salivary gland cancer in Southern Brazil: a prognostic study of 107 cases

Background: Salivary gland cancers (SGC) represent an uncommon group of heterogeneous tumors. We performed a retrospective survey of SGC diagnosed in a reference center for treatment of malignant tumors from the south of Brazil aiming to determine the prognostic value of demographic, clinic and pathologic features. Material and Methods: Cases diagnosed as SGC between 2006 and 2016 were retrospectively collected. Medical records were examined to extract demographic, clinic, pathologic and follow-up information. Results: One-hundred and seven cases of SGC were identified. The most common SGC were mucoepidermoid carcinoma (MEC) (n = 39) followed by adenoid cystic carcinoma (AdCC) (n = 29). Among AdCCs, 55.2% of cases were classified as cribriform, 27.6% as tubular and 17.2% as solid. The tubular subtype had the highest percentage of cases with perineural invasion (p=0.01). Among MEC, 61.5% of cases were classified as low grade, 15.4% as intermediate grade and 19.9% as high grade. Low grade MEC had the lowest percentage of cases with perineural invasion (p=0.04). The 5-year survival for loco-regional control, disease-free survival (DFS) and disease-specific survival were 75%, 70% and 84%, respectively. The following features were associated with poor DFS: advanced age (p=0.03), rural residency (p=0.01), being a smoker or former smoker (p=0.01), pain (p=0.03), nodal metastasis (p<0.001), need for chemotherapy (p=0.02), neck dissection (p=0.04), perineural invasion (p=0.01), and being diagnosed with AdCC compared to MEC (p=0.02). Conclusions: The clinco-demographic and pathologic features identified as prognostic factors reveal the profile of patients at increased risk of recurrence and who would benefit from closer follow-up

Alternativas de establecimiento de praderas.

Se describen tecnologías de establecimiento de praderas en empresas ganaderas de la altillanura de los Llanos Orientales de Colombia, para intensificar la producción de carne y leche de los sistemas productivos. Se indican las fincas seleccionadas, sus características agroecológicas, las labores de establecimiento, preparación y siembra de praderas y los resultados obtenidos en términos de producción de forraje y composición botánica. Se evaluó la producción animal y se observó que la introducción y manejo adecuado de leguminosas de las praderas, aumenta los nutrientes de la dieta y mejora la ganancia de peso en los animalesPastos y forraje

TrkB-targeted therapy for mucoepidermoid carcinoma

The brain-derived neurotrophic factor (BDNF)/tyrosine receptor kinase B (TrkB) pathway was previously associated with key oncogenic outcomes in a number of adenocarcinomas. The aim of our study was to determine the role of this pathway in mucoepidermoid carcinoma (MEC). Three MEC cell lines (UM-HMC-2, H253 and H292) were exposed to Cisplatin, the TrkB inhibitor, ANA-12 and a combination of these drugs. Ultrastructural changes were assessed through transmission electron microscopy; scratch and Transwell assays were used to assess migration and invasion; and a clonogenic assay and spheroid-forming assay allowed assessment of survival and percentage of cancer stem cells (CSC). Changes in cell ultrastructure demonstrated Cisplatin cytotoxicity, while the effects of ANA-12 were less pronounced. Both drugs, used individually and in combination, delayed MEC cell migration, invasion and survival. ANA-12 significantly reduced the number of CSC, but the Cisplatin effect was greater, almost eliminating this cell population in all MEC cell lines. Interestingly, the spheroid forming capacity recovered, following the combination therapy, as compared to Cisplatin alone. Our studies allowed us to conclude that the TrkB inhibition, efficiently impaired MEC cell migration, invasion and survival in vitro, however, the decrease in CSC number, following the combined treatment of ANA-12 and Cisplatin, was less than that seen with Cisplatin alone; this represents a limiting factor

Oral Melanoacanthoma And Oral Melanotic Macule: A Report Of 8 Cases, Review Of The Literature, And Immunohistochemical Analysis

Oral melanoacanthoma (MA) is a rare, benign pigmented lesion, similar to cutaneous MA, characterized by hyperplasia of spinous keratinocytes and dendritic melanocytes. The pathogenesis of oral MA remains uncertain, although its clinical behavior is suggestive of a reactive origin. The most common intraoral sites are the buccal mucosa, lip, palate and gingiva. The average age of presentation is 28 years, mainly in blacks, with a strong female predilection. The oral melanotic macule (MM) is a small, well-circumscribed brown-to-black macule that occurs on the lips and mucous membranes. The etiology is not clear and it may represent a physiologic or reactive process. The average age of presentation is 43 years, with a female predilection. A biopsy is recommended to distinguish these lesions from each other and from other oral melanocytic lesions. We depict four cases each of oral MA and MM, affecting Caucasian and Latin American mestizo patients. The clinicopathological features of these cases reflect its ample spectrum, and to the best of our knowledge, it is the first example of oral MA affecting a Caucasian boy reported in the English literature. Therefore oral MA and MM should be considered in the differential diagnosis of pigmented lesions in the oral mucosa in these populations. © Medicina Oral.125E374E379Mishima, Y., Pinkus, H., Benign mixed tumor of melanocytes and malpighian cells. Melanoacanthoma: Its relationship to Bloch's benign non-nevoid melanoepithelioma (1960) Arch Dermatol, 81, pp. 539-550Buchner, A., Merrell, P.W., Carpenter, W.M., Relative frequency of solitary melanocytic lesions of the oral mucosa (2004) J Oral Pathol Med, 33, pp. 550-557Wright, J.M., Binnie, W.H., Byrd, D.L., Dunsworth, A.R., Intraoral melanoacanthomas (1983) J Periodontol, 54, pp. 107-111Buchner, A., Merrell, P., Hanson, L., Leider, A., Melanocytic hyperplasia of the oral mucosa (1991) Oral Surg, Oral Med Oral Pathol, 71, pp. 58-62Wright, J.M., Intraoral melanoacanthoma: A reactive melanocytic hyperplasia. Case report (1988) J Periodontol, 59, pp. 53-55Tomich, C., Zunt, S.L., Melanoacanthosis (melanoacanthoma) of the oral mucosa (1990) J Dermatol Surg Oncol, 16, pp. 231-236Contreras, E., Carlos, R., Oral melanoacanthosis (melanoachantoma): Report of a case and review of the literature (2005) Med Oral Patol Oral Cir Bucal, 10 (1), pp. 11-12,9-11Fornatora, M.L., Reich, R.F., Haber, S., Solomon, F., Freedman, P.D., Oral melanoacanthomas: A report of 10 cases, review of the literature, and immunohistochemical analysis for HMB-45 reactivity (2003) Am J Dermatopathol, 25, pp. 12-15Matsuoka, L.Y., Glasser, S., Barsky, S., Melanoacanthoma of the lip (1979) Arch Dermatol, 115, pp. 1116-1117Goode, R.K., Crawford, B.E., Callihan, M.D., Neville, B.W., Oral melanoacanthoma. Review of the literature and report of ten cases (1983) Oral Surg Oral Med Oral Pathol, 56, pp. 622-628Scheneider, L.C., Mesa, M.L., Haber, S.M., Melanoacanthoma of the oral mucosa (1981) Oral Surg Oral Med Oral Pathol, 52, pp. 284-287Fatahzadeh, M., Sirois, D.A., Multiple intraoral melanoacanthomas: A case report with unusual findings (2002) Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 94, pp. 54-56Ho, K.K., Dervan, P., O'Loughlin, S., Powell, F.C., Labial melanotic macule: A clinical, histopathologic, and ultrastructural study (1993) J Am Acad of Dermatol, 28, pp. 33-39Sexton, F.M., Maize, J.C., Melanotic macules and melanoacanthomas of the lip. A comparative study with census of the basal melanocyte population (1987) Am J Dermatopathol, 9, pp. 438-444Horlick, H.P., Walther, R.R., Zegarelli, D.J., Silvers, D.N., Eliezri, Y.D., Mucosal melanotic macule, reactive type: A simulation of melanoma (1988) J Am Acad Dermatol, 19, pp. 786-791Buchner, A., Hansen, L.S., Pigmented nevi of the oral mucosa: A clinicopathologic study of 32 new cases and review of 75 cases from the literature: Part I. A clinicopathologic study of 32 new cases (1979) Oral Surg Oral Med Oral Pathol, 48, pp. 131-142Barker, B.F., Carpenter, W.M., Daniels, T.E., Kahn, M.A., Leider, A.S., Lozada-Nur, F., (1997) Oral mucosal melanomas: The WESTOP Banff workshop proceedings, 83, pp. 672-679. , Western Society of Teachers of Oral Pathology. Oral Surg Oral Med Oral Pathol Oral Radiol EndodBarrett, A.W., Raja, A.M., The immunohistochemical identification of human oral mucosal melanocytes (1997) Arch Oral Biol, 42, pp. 77-8

Convolutional neural network-based clinical predictors of oral dysplasia: class activation map analysis of deep learning results

Oral cancer/oral squamous cell carcinoma is among the top ten most common cancers globally, with over 500,000 new cases and 350,000 associated deaths every year worldwide. There is a critical need for objective, novel technologies that facilitate early, accurate diagnosis. For this purpose, we have developed a method to classify images as “suspicious” and “normal” by performing transfer learning on Inception-ResNet-V2 and generated automated heat maps to highlight the region of the images most likely to be involved in decision making. We have tested the developed method’s feasibility on two independent datasets of clinical photographic images of 30 and 24 patients from the UK and Brazil, respectively. Both 10-fold cross-validation and leave-one-patient-out validation methods were performed to test the system, achieving accuracies of 73.6% (±19%) and 90.9% (±12%), F1-scores of 97.9% and 87.2%, and precision values of 95.4% and 99.3% at recall values of 100.0% and 81.1% on these two respective cohorts. This study presents several novel findings and approaches, namely the development and validation of our methods on two datasets collected in different countries showing that using patches instead of the whole lesion image leads to better performance and analyzing which regions of the images are predictive of the classes using class activation map analysis

MutSα expression predicts a lower disease-free survival in malignant salivary gland tumors: an immunohistochemical study

Background: Appropriate DNA replication is vital to maintain cell integrity at the genomic level. Malfunction on DNA repair mechanisms can have implications related to tumor behavior. Our aim was to evaluate the expression of key complexes of the DNA mismatch-repair system MutSα (hMSH2-hMSH6) and MutSβ (hMSH2-hMSH3) in a panel comprising the most common benign and malignant salivary gland tumors (SGT), and to determine their association with disease-free survival. Material and Methods: Ten cases of normal salivary gland (NSG) and 92 of SGT (54 benign and 38 malignant) were retrieved. Immunohistochemistry was performed for hMSH2, hMSH3, hMSH6. Scanned slides were digitally analyzed based on the percentage of positive cells with nuclear staining. Cases were further classified in MutSαhigh and MutSβhigh based on hMSH2-hMSH6 and hMSH3-hMSH6 expression, respectively. Results: hMSH3 expression was lower in malignant SGT compared to NSG and benign cases. Adenoid cystic carcinoma (ACC) cases with perineural invasion presented a lower percentage of hMSH3 positive cells. hMSH6 was downregulated in both benign and malignant SGT compared to NSG. Malignant SGT cases with MutSαhigh expression had lower disease-free survival compared to MutSαlow cases. A 10.26-fold increased risk of presenting local recurrence was observed. Conclusions: Our findings suggest that a lack of hMSH3 protein function is associated with a more aggressive phenotype (malignancy and perineural invasion) and that MutSα overexpression predicts a poor clinical outcome in malignant SGT

The impact of flooding on aquatic ecosystem services

Flooding is a major disturbance that impacts aquatic ecosystems and the ecosystem services that they provide. Predicted increases in global flood risk due to land use change and water cycle intensification will likely only increase the frequency and severity of these impacts. Extreme flooding events can cause loss of life and significant destruction to property and infrastructure, effects that are easily recognized and frequently reported in the media. However, flooding also has many other effects on people through freshwater aquatic ecosystem services, which often go unrecognized because they are less evident and can be difficult to evaluate. Here, we identify the effects that small magnitude frequently occurring floods ( 100-year recurrence interval) have on ten aquatic ecosystem services through a systematic literature review. We focused on ecosystem services considered by the Millennium Ecosystem Assessment including: (1) supporting services (primary production, soil formation), (2) regulating services (water regulation, water quality, disease regulation, climate regulation), (3) provisioning services (drinking water, food supply), and (4) cultural services (aesthetic value, recreation and tourism). The literature search resulted in 117 studies and each of the ten ecosystem services was represented by an average of 12 ± 4 studies. Extreme floods resulted in losses in almost every ecosystem service considered in this study. However, small floods had neutral or positive effects on half of the ecosystem services we considered. For example, small floods led to increases in primary production, water regulation, and recreation and tourism. Decision-making that preserves small floods while reducing the impacts of extreme floods can increase ecosystem service provision and minimize losses

MDM2 Integrates Cellular Respiration and Apoptotic Signaling through NDUFS1 and the Mitochondrial Network

Signaling diversity and subsequent complexity in higher eukaryotes is partially explained by one gene encoding a polypeptide with multiple biochemical functions in different cellular contexts. For example, mouse double minute 2 (MDM2) is functionally characterized as both an oncogene and a tumor suppressor, yet this dual classification confounds the cell biology and clinical literatures. Identified via complementary biochemical, organellar, and cellular approaches, we report that MDM2 negatively regulates NADH:ubiquinone oxidoreductase 75 kDa Fe-S protein 1 (NDUFS1), leading to decreased mitochondrial respiration, marked oxidative stress, and commitment to the mitochondrial pathway of apoptosis. MDM2 directly binds and sequesters NDUFS1, preventing its mitochondrial localization and ultimately causing complex I and supercomplex destabilization and inefficiency of oxidative phosphorylation. The MDM2 amino-terminal region is sufficient to bind NDUFS1, alter supercomplex assembly, and induce apoptosis. Finally, this pathway is independent of p53, and several mitochondrial phenotypes are observed in Drosophila and murine models expressing transgenic Mdm2