Loss of Expression and Function of SOCS3 Is an Early Event in HNSCC: Altered Subcellular Localization as a Possible Mechanism Involved in Proliferation, Migration and Invasion

Background: Suppressor of cytokine signaling 3 (SOCS3) is an inducible endogenous negative regulator of signal transduction and activator of transcription 3 (STAT3). Epigenetic silencing of SOCS3 has been shown in head and neck squamous cell carcinoma (HNSCC), which is associated with increased activation of STAT3. There is scarce information on the functional role of the reduction of SOCS3 expression and no information on altered subcellular localization of SOCS3 in HNSCC.Methodology/Principal Findings: We assessed endogenous SOCS3 expression in different HNSCC cell lines by RT-qPCR and western blot. Immunofluorescence and western blot were used to study the subcellular localization of endogenous SOCS3 induced by IL-6. Overexpression of SOCS3 by CMV-driven plasmids and siRNA-mediated inhibition of endogenous SOCS3 were used to verify the role of SOCS3 on tumor cell proliferation, viability, invasion and migration in vitro. In vivo relevance of SOCS3 expression in HNSCC was studied by quantitative immunohistochemistry of commercially-available tissue microarrays. Endogenous expression of SOCS3 was heterogeneous in four HNSCC cell lines and surprisingly preserved in most of these cell lines. Subcellular localization of endogenous SOCS3 in the HNSCC cell lines was predominantly nuclear as opposed to cytoplasmic in non-neoplasic epithelial cells. Overexpression of SOCS3 produced a relative increase of the protein in the cytoplasmic compartment and significantly inhibited proliferation, migration and invasion, whereas inhibition of endogenous nuclear SOCS3 did not affect these events. Analysis of tissue microarrays indicated that loss of SOCS3 is an early event in HNSCC and was correlated with tumor size and histological grade of dysplasia, but a considerable proportion of cases presented detectable expression of SOCS3.Conclusion: Our data support a role for SOCS3 as a tumor suppressor gene in HNSCC with relevance on proliferation and invasion processes and suggests that abnormal subcellular localization impairs SOCS3 function in HNSCC cells.

Annexin A1 subcellular expression in laryngeal squamous cell carcinoma

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Apoptosis in tongue squamous cell carcinoma and its correlation with clinically occult cervical metastasis

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Expression pattern of claudins 1 and 3-an auxiliary tool in predicting behavior of mucoepidermoid carcinoma of salivary gland origin

Claudins (CLDNs) are a family of membrane proteins important for permeability of tight junctions. They have also been implicated in carcinogenesis and tumor progression. We analyzed patterns of distribution and intensity of expression of CLDNs 1, 3, 4, and 7 in mucoepidermoid carcinoma (MEC) of salivary gland in 39 patients. Correlations between the expression of CLDNs, tumor grade, and survival were explored. In immunohistochemical analysis, high expression of CLDN 1 was seen in low-grade MEC, and it appeared to be a suitable auxiliary marker of good prognosis. It classified MEC similarly to histological grading in 89.7% of cases (p=0.001). High CLDN 3 expression was seen in intermediate-and high-grade MEC, while it was low in low-grade MEC. CLDN 3 intensity correctly categorized tumors into grades in 71.8% of cases (p=0.017). However, in multivariate analysis CLDN 1 and CLDN 3 did not achieve significance over tumor grade in predicting patient behavior. We conclude that analysis of staining intensities of CLDN 1 and 3 is useful as an auxiliary diagnostic and prognostic tool in patients with salivary gland MEC.

Macro- and microstructure of the superior cervical ganglion in dogs, cats and horses during maturation

The superior cervical ganglion (SCG) provides sympathetic input to the head and neck, its relation with mandible, submandibular glands, eyes (second and third order control) and pineal gland being demonstrated in laboratory animals. In addition, the SCG's role in some neuropathies can be clearly seen in Horner's syndrome. In spite of several studies published involving rats and mice, there is little morphological descriptive and comparative data of SCG from large mammals. Thus, we investigated the SCG's macro- and microstructural organization in medium (dogs and cats) and large animals (horses) during a very specific period of the post-natal development, namely maturation (from young to adults). The SCG of dogs, cats and horses were spindle shaped and located deeply into the bifurcation of the common carotid artery, close to the distal vagus ganglion and more related to the internal carotid artery in dogs and horses, and to the occipital artery in cats. As to macromorphometrical data, that is ganglion length, there was a 23.6% increase from young to adult dogs, a 1.8% increase from young to adult cats and finally a 34% increase from young to adult horses. Histologically, the SCG's microstructure was quite similar between young and adult animals and among the 3 species. The SCG was divided into distinct compartments (ganglion units) by capsular septa of connective tissue. Inside each ganglion unit the most prominent cellular elements were ganglion neurons, glial cells and small intensely fluorescent cells, comprising the ganglion's morphological triad. Given this morphological arrangement, that is a summation of all ganglion units, SCG from dogs, cats and horses are better characterized as a ganglion complex rather than following the classical ganglion concept. During maturation (from young to adults) there was a 32.7% increase in the SCG's connective capsule in dogs, a 25.8% increase in cats and a 33.2% increase in horses. There was an age-related increase in the neuronal profile size in the SCG from young to adult animals, that is a 1.6-fold, 1.9-fold and 1.6-fold increase in dogs, cats and horses, respectively. on the other hand, there was an age-related decrease in the nuclear profile size of SCG neurons from young to adult animals (0.9-fold, 0.7-fold and 0.8-fold in dogs, cats and horses, respectively). Ganglion connective capsule is composed of 2 or 3 layers of collagen fibres in juxtaposition and, as observed in light microscopy and independently of the animal's age, ganglion neurons were organised in ganglionic units containing the same morphological triad seen in light microscopy. Copyright (c) 2007 S. Karger AG, Basel.

Angiogenesis and skin carcinomas with skull base invasion: A case-control study

Background. Some skin carcinomas may be very aggressive. Intensity of angiogenesis, measured by intratumoral vessel density using expression of CD34, has been associated with tumor aggressiveness. In this study, the expression of CD34 in basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) with skull base invasion was compared with that in tumors with good outcome.Methods. Expression of CD34 was graded as mild, moderate, and intense, in 24 BCCs and 11 SCCs with skull base invasion. The control group included 23 BCCs and 10 SCCs.Results. Intense expression of CD34 was noted in 25.00% of BCCs with skull base invasion, compared with 4.35% in the control group (p =.058). Regarding SCCs, intense expression of CD34 was found in 54.55% of aggressive tumors, compared with 10.00% in the control group (p = 133).Conclusions. A trend toward denser microvascular angiogenesis was observed in both BCCs and SCCs with skull base invasion compared with less aggressive controls. (C) 2004 Wiley Periodicals, Inc.

Second, primary tumours in patients with mouth cancer

Over the last decades, technical-scientific advances of oncology have brought about an increased survival rate for cancer patients. As a result, oncologists have detected an increased number of patients presenting with other neoplasms. This research aimed to analyze factors related to demography and to the anatomic site in patients having a FPT of the mouth who developed a SPT. Medical charts of 848 patients neoplasm admitted for treatment at the Head and Neck Surgery Department of the Hospital do Cancer, Antonio Candido Camargo, Brazil, from January of 1984 to December, were analysed. of these, 12 6 developed a SPT. 49.21 % were from 51 to 65 years of age, while 83.33% were of the male gender and Caucasian. Regarding FPT site 38.89% were of the tongue, and 28.5% were of the floor of the mouth. The esophagus, excepting skin (13.49%), was more often subject to SPT (11.9%), of these 74.6% were metachronic, 15.87% simultaneous and 9.52% synchronous.

Morphology of the head and frontal gland in neotropical Nasutitermitinae (Isoptera, Termitidae)

The Nasutitermitinae species are the most diverse and derived of the Isoptera. The phylogeny of this subfamily has been a point of divergence. In an attempt to solve this problem, we propose the use of the morphological features of the head, frontal gland and its associated muscles as phylogenetic characters in some Nasutitermitinae genera. Results found about the head and frontal gland morphology are discussed and suggested to be used in future systematic studies of termites.

Possible implication of Mdm2 as a prognostic marker in invasive laryngeal carcinoma

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Detection of HPV in mouth floor squamous cell carcinoma and its correlation with clinicopathologic variables, risk factors and survival

The human papillomavirus (HPV) has been historically associated with head and neck cancers, although its role in oral carcinogenesis remains poorly defined. The purpose of this study was to investigate the prevalence of HPV in mouth floor squamous cell carcinoma and correlate it with clinicopathologic variables, risk factors and survival. HPV presence was evaluated by nested polymerase chain reaction (nPCR) in 29 paraffin-embedded specimens of mouth floor squamous cell carcinoma. HPV DNA was detected in 17.2% (5 of 29) of the specimens; the highest prevalence was observed in non-smoking patients over the age of 60 years. All HPV DNA positive specimens were detected in men with clinical stage III and IV lesions, being most of which were moderately differentiated. Despite this correlation there were no statistically significant differences observed among the analyzed variables, including patients' survival. The relatively low incidence of HPV DNA present in these tumors suggests that this virus does not, by itself, have a significant role in the development of mouth floor squamous cell carcinoma. J Oral Pathol Med (2008) 37: 593-598

Comparison of exfoliative pap stain and AgNOR counts of the tongue in smokers and nonsmokers

Objective To compare exfoliative cytology from the oral mucosa of smokers and nonsmokers, with emphasis on proliferative activity. Methods Exfoliative cytology specimens were obtained from clinical normal mucosa from the lateral border of the tongue in 30 nonsmokers and 30 smokers ranging in age from 40 to 70 years of age, who were seen at the Heart Institute's Patient Center and the Smoking Cessation Program of the University Hospital, University of São Paulo Medical School (InCor-HCFMUSP). The cytologic specimens were evaluated by Papanicolaou staining and AgNOR quantification in order to evaluate the presence of cytological alterations suggestive of inflammation, dysplasia, keratinization, and proliferative activity of epithelial cells. Results Only Papanicolaou Class I and Class II smears were observed. Inflammatory alterations were found in 90% of smokers and in 87% of nonsmokers. The number of AgNORs/nucleus differed significantly between smokers and nonsmokers (3.372 ± 0.375 versus 2.732 ± 0.236). Conclusions Within the limitations of this research, the results indicate higher proliferative activity in smoking patients compared to nonsmoking patients, even in the absence of clinical lesions. © The Author(s) 2008.

Lip cavernous hemangioma in a young child

Hemangiomas are benign tumors of infancy and childhood, characterized by a phase of fast growth with endothelial cell proliferation, occurring in 10-12% of children at 1 year of age. It is known that hemangiomas of infancy are most commonly located on the head and neck region (around 60% of cases) and occur more frequently in the lips, tongue, and palate. Approximately 50% of hemangiomas have complete resolution, and 90% of them are resolved up to the age of 9. Complications occur in only 20% of the cases, the most common problem being ulceration with or without infection. The treatment depends on lesion location, size and evolution stage, and the patient's age. Surgery is usually indicated when there is no response to systemic treatments, or even for esthetic reasons, being performed as a simple excision in combination or not with plastic surgery. This paper reports a case of lip cavernous hemangioma in a 4-year-old child, who was submitted to 3 sessions of vascular sclerosis due to the size of the lesion, before undergoing simple excision of the hemangioma. Two years of postoperative clinical follow-up shows treatment success with no recurrence of the lesion.

Intermuscular lipoma of the submandibular space

Deep lipomas, especially in the head and neck region, are uncommon. This report describes the case of a patient with a large intermuscular lipoma of the submandibular space, which had been present for 10 years and was diagnosed by computed tomography. The clinical, imaging, and histopathological features, as well as the management of the tumor, are described.

Jugular thrombophlebitis in horses: A review of fibrinolysis, thrombus formation, and clinical management

Thrombophlebitis of the jugular vein is commonly observed in horses, particularly during intensive care, and leads to local and systemic inflammatory responses as well as head and neck circulatory impairment. Thrombolytic therapy is widely used in human practice with the aim of thrombus dissolution and recanalization of the injured vessels. There are similarities between human and horse coagulation and fibrinolytic processes. This review examines the fibrinolytic system, thrombus formation, and the clinical management of jugular thrombophlebitis, including thrombolytic therapy. There is evidence that early regional thrombolytic therapy for jugular thrombophlebitis in horses may be effective to achieve sustained recanalization.