Antisense transcription at the TRPM2 locus as a novel prognostic marker and therapeutic target in prostate cancer.

Overwhelming evidence indicates that cancer is a genetic disease caused by the accumulation of mutations in oncogenes and tumor suppressor genes. It is also increasingly apparent, however, that cancer depends not only on mutations in these coding genes but also on alterations in the large class of non-coding RNAs. Here, we report that one such long non-coding RNA, TRPM2-AS, an antisense transcript of TRPM2, which encodes an oxidative stress-activated ion channel, is overexpressed in prostate cancer (PCa). The high expression of TRPM2-AS and its related gene signature were found to be linked to poor clinical outcome, with the related gene signature working also independently of the patient's Gleason score. Mechanistically, TRPM2-AS knockdown led to PCa cell apoptosis, with a transcriptional profile that indicated an unbearable increase in cellular stress in the dying cells, which was coupled to cell cycle arrest, an increase in intracellular hydrogen peroxide and activation of the sense TRPM2 gene. Moreover, targets of existing drugs and treatments were found to be consistently associated with high TRPM2-AS levels in both targeted cells and patients, ultimately suggesting that the measurement of the expression levels of TRPM2-AS allows not only for the early identification of aggressive PCa tumors, but also identifies a subset of at-risk patients who would benefit from currently available, but mostly differently purposed, therapeutic agents.

Mandibular metastatic hepatocellular carcinoma: report of a case involving severe and uncontrollable hemorrhage.

Hepatocellular carcinoma (HCC) is a malignant tumor with a marked tendency to spread through the portal system. Metastases from HCC usually involve lungs, surrenal glands, the skeletal and gastroenteric systems, spleen, heart and kidneys. Secondary localizations to the mandible are rare. Generally, bone metastases from HCC appear as osteolytic lesions more likely localized to the ribs, spine, femor, omer, sternum, and then to the mandible. Mandibular metastatic HCC is hemorrhagic in nature because of its hypervascularity. Any diagnostic maneuver that could end in bleeding should be avoided. Non-invasive diagnostic procedures such as computer tomography (CT) scan should be preferred. Among the invasive diagnostic procedures, only fine needle biopsy should be attempted and palliative radiotherapy could be useful for the control of local symptoms. A case report of a hemorrhagic mandibular metastatic HCC that had to be treated surgically, in order to control the severe and profuse bleeding, is presented.

Were protein internal repeats formed by "bricolage"?

Is evolution an engineer, or is it a tinkerer--a "bricoleur"--building up complex molecules in organisms by increasing and adapting the materials at hand? An analysis of completely sequenced genomes suggests the latter, showing that increasing repetition of modules within the proteins encoded by these genomes is correlated with increasing complexity of the organism.

Temporally restricted expression of transcription factor betaFTZ-F1: significance for embryogenesis, molting and metamorphosis in Drosophila melanogaster.

FTZ-F1, a member of the nuclear receptor superfamily, has been implicated in the activation of the segmentation gene fushi tarazu during early embryogenesis of Drosophila melanogaster. We found that an isoform of FTZ-F1, betaFTZ-F1, is expressed in the nuclei of almost all tissues slightly before the first and second larval ecdysis and before pupation. Severely affected ftz-f1 mutants display an embryonic lethal phenotype, but can be rescued by ectopic expression of betaFTZ-F1 during the period of endogenous betaFTZ-F1 expression in the wild type. The resulting larvae are not able to molt, but this activity is rescued again by forced expression of betaFTZ-F1, allowing progression to the next larval instar stage. On the other hand, premature expression of betaFTZ-F1 in wild-type larvae at mid-first instar or mid-second instar stages causes defects in the molting process. Sensitive periods were found to be around the time of peak ecdysteroid levels and slightly before the start of endogenous betaFTZ-F1 expression. A hypomorphic ftz-f1 mutant that arrests in the prepupal stage can also be rescued by ectopic, time-specific expression of betaFTZ-F1. Failure of salivary gland histolysis, one of the phenotypes of the ftz-f1 mutant, is rescued by forced expression of the ftz-f1 downstream gene BR-C during the late prepupal period. These results suggest that betaFTZ-F1 regulates genes associated with ecdysis and metamorphosis, and that the exact timing of its action in the ecdysone-induced gene cascade is important for proper development.

The Otx2 homeoprotein regulates expression from the gonadotropin-releasing hormone proximal promoter.

The GnRH gene is expressed exclusively in a highly restricted population of approximately 800 neurons in the mediobasal hypothalamus in the mouse. The Otx2 homeoprotein has been shown to colocalize with GnRH in embryonic mouse brain. We have identified a highly conserved bicoid-related Otx target sequence within the proximal promoter region of the GnRH gene from several species. This element from the rat GnRH promoter binds baculovirus-expressed Otx2 protein and Otx2 protein in nuclear extracts of a hypothalamic GnRH-expressing neuronal cell line, GT1-7. Transient transfection assays indicate that the GnRH promoter Otx/bicoid site is required for specific expression of the GnRH gene in GT1-7 cells and that it can confer specificity to a neutral Rous sarcoma virus (RSV) promoter in GT1-7 cells but not in NIH3T3 cells. Overexpression of mouse Otx2 in GT1-7 cells induces expression of a GnRH promoter plasmid, an effect that is dependent upon the Otx binding site. Thus, the GnRH proximal promoter is regulated by the Otx2 homeoprotein. Finally, we have now demonstrated the presence of Otx2 protein in the GnRH neurons of the adult mouse hypothalamus. These data suggest that Otx2 is important in the development of the GnRH neuron and/or in the maintenance of GnRH expression in the adult mouse hypothalamus.

[Oncologic post-resection reconstruction of mandibular defects]. / Ricostruzione post-resezione oncologica dei difetti della mandibola.

BACKGROUND AND AIM: If not reconstructed, mandibular defects resulting from oncological surgery can leave major functional and cosmetic sequelae which may impede these patients from returning to professional and family life. Reconstruction may be immediate or deferred, but the authors clearly recommend immediate reconstruction. METHODS: An analysis is made of the different techniques used for the reconstruction of mandibular defects, specifying those which are currently used and the situations in which they are applied. The advantages and disadvantages of microsurgical flaps and pedicled flaps are emphasised. The immediate use of endosseous implants is also discussed. RESULTS: The results of the various types of reconstruction are compared from a cosmetic and functional point of view. The latter includes a study of the quality of speech, deglutition, mastication and labial competence. Mastication is studied in two types of patients: those with osteointegrated implants with neomandibular reconstruction and those in whom osteointegrated implants were not used. All these patients survived 5 years after surgery. CONCLUSIONS: The authors recommend the immediate reconstruction of mandibular defects. Microsurgical flaps and pedicled flaps can be used for this purpose. Bone flaps may be used for endosseous titanium implants, whereas osseous flaps which do not provide a sufficient guarantee of rehabilitation should not be used. Implants should be inserted during oncological surgery, since postoperative radiotherapy may alter osteointegration of titanium implants are then used. The overall survival of these patients depends on the margins of local resection which are much wider using these techniques.

Diffuse acute cellulitis with severe neurological sequelae. A clinical case.

The incidence of head and neck odontogenic infections considerably diminished in the last decades due to appropriate antibiotic therapy. Herein we describe a case of acute diffuse facial cellulitis following tooth extraction in a patient with no apparent risk factor. During the acute process, injury was caused to the hypoglossal, vagal, glossopharyngeal and recurrent nerves of both sides. For this reason the patient currently has a nasogastric line for enteral feedings and a tracheotomy tube, which significantly affects his quality of life.

TargetFinder: searching annotated sequence databases for target genes of transcription factors.

UNLABELLED: TargetFinder is a new software tool to search a database of annotated sequences for transcription factor binding sites located in context with other important transcription regulatory signals and regions, like the TATA element, the promoter, and so on, thereby greatly reducing the background usually associated with this kind of search. AVAILABILITY: The TargetFinder Web service is available at http://hercules.tigem.it/TargetFinder.html CONTACT: giovanni.lavorgna@hsr.it

Papillary carcinoma of the base of the tongue. Case clinic.

Ectopic lingual thyroid tissue is an uncommon developmental anomaly. Tumours of identical pathological characteristics as those arising in the eutropic thyroid tissue, may be present in ectopic locations. There are very few cases of malignant tumours reported in the literature. Here we report a review of this pathology and we describe a case of a papillary carcinoma of the base of the tongue, located in ectopic lingual thyroid tissue, in a 66 year-old white man, complaining of dysphagia and oral bleeding. Surgical treatment was carried out, consisting of radical resection of the right hemineck, tumour resection, right hemiglossectomy and total thyroidectomy. Postoperative treatment with 131I and substitutive thyroid hormonal therapy was prescribed.

[Three-dimensional imaging with computerized tomography. Etiologic considerations and methods for studying temporo-mandibular joints]. / Imaging tridimensionale con Tomografia Computerizzata. Presupposti eidologici e metodologia dello studio dell'articolazione temporo-mandibolare.

INTRODUCTION: The temporomandibular joint (TMJ) had always been studied with conventional tomography and, more recently, with Magnetic Resonance Imaging. Computed Tomography (CT) can demonstrate periarticular soft tissues only. Recently, the introduction of three-dimensional (3D) CT reconstructions with dedicated softwares permitted to demonstrate functional changes in the TMJ with a simple and accurate measurement system. MATERIAL AND METHODS: We examined 347 patients with TMJ disorders using two different 3rd generation CT units and acquiring two series of scans, with the mouth closed and in maximum opening. 3D reconstructions on predefined planes were obtained with a dedicated software and integrated with the electronic measurements of the following morphologic and functional parameters: zygomatic tubercle height, axis of sagittal inclination of the mandibular condyle, TMJ movement range and changes in torsion/dislocation of condylar angle. RESULTS AND DISCUSSION: CT showed the TMJ easily. This examination lasts about 10 minutes, plus 10-15 more minutes for 3D reconstructions. Some artifacts were found on 3D images--thresholding artifacts, defined as pseudoforamina and pseudocalcifications. Neverthless, 3D imaging can easily demonstrate an articular district which is very complex in both morphology and function, supporting or replacing similar subconscious processes made by radiologists themselves. This technique was well accepted by all our patients and functional results were always in agreement with clinical findings. Moreover, CT is the only technique showing both TMJ sides at the same time. Our measurement system was easy to perform, repeatable and comparable also thanks to its potentials of standardization on different CT units. CONCLUSIONS: CT with 3D reconstructions appears the gold standard technique for functional TMJ studies. Even though it provides no information on the joint disk--which MRI does--3D CT permits easy and accurate measurements of both TMJ sides which can support clinical findings.

[A statistical contribution to fractures of the maxillofacial area]. / Contributo statistico alle fratture del distretto maxillo-facciale.

Twenty years experience (from 1975 to 1994), on 483 patients with injury of the maxillo-facial area observed at the Department of Maxillo-Facial Surgery of the University of Naples "Federico II" is reported. The analysis of the data, according to the literature, shows that the sex most involved is male (76%) with a prevalence of the second decade of life (38%); street injury is the most frequent cause of maxillo-facial fracture (48.5%), while in 1.6% the cause is not reported. Mandibular fractures (57%), particularly those of the left condyle, are more frequent. The type of treatment is discussed in relation to the site of fracture, in particular the therapy of the condylar ones. In fact, in the treatment of those fractures the authors use sequential functional plates, the first of whose presents a monolateral byte, homolateral to the injury, while the second a contralateral guide in closure. The use of such plates, even if it doesn't often obtain a perfect anatomical realignment of the fracture, allows an optimal functional rehabilitation due to the potential of remodelling of the condyle, avoiding complications related to surgical intervention.

[Consideration on a case of carcinoma ex pleomorphic adenoma of the parotid gland]. / Considerazioni su di un caso di carcinoma ex adenoma pleomorfo della parotide.

The authors report a case of carcinoma in an ex pleomorphic adenoma of the parotid gland that was recently referred to their attention. This form of carcinoma is not very frequent and in the literature it is reported in a percentage of cases ranging from 1.5 to 12%. The pathogenesis of this neoplasia is controversial and at the present state of the art there are authors who support the hypothesis of a malignant transformation of a previous pleomorphic adenoma, and those who sustain the onset of the tumour ex novo. At present, there is a tendency to differentiate the carcinoma ex pleomorphic adenoma from the malignant mixed tumour: the histological analysis of the former in fact shows a benign stromal component typical of pleomorphic adenoma associated with a malignant epithelial component, whereas in the malignant mixed tumour both the mesenchymal and epithelial components are malignant. The authors use this case report as a starting point to review their 20-year experience, of pleomorphic adenoma in order to evaluate the behaviour of this tumour, above all in relation to the phenomenon of recidivation and cancerization. They report recidivation in 3.5% of cases and no malignant degeneration. The surgical approach used varied depending on the site and size of the neoformation, as well as on whether the tumour was primary or recurrent.

[Injuries of the nasal bone in boxing]. / I traumi dello scheletro nasale nella pratica pugilistica.

Nose fractures in boxers ar clamfied and their pathogenesis described. Therapy is related to boxer's activity; in fact in boxers in activity the respiratory tract was reinstated; in that one retired over respiratory tract, nose aesthetics was treated too.

[The correlation between sonoarthrographic and arthroscopic data. Its verification in a clinical case]. / Correlazione tra dati sonoartrografici ed artroscopia. Verifica su di un caso clinico.

Surgical arthroscopy is an important option in the treatment of TMJ pain and disfunction. Also sonography of the TMJ is a technique that with recent improvements graphically displays and analyzes joint sounds. A comparison was performed between presurgical data obtained by sonography, clinical findings obtained by surgical arthroscopy, and post surgical control performed by sonography. Precise correlation between these data was found in the case reported.

[Occlusal re-equilibrium in patients with the craniomandibular dysfunctional syndrome. The use of a functional plate]. / Il riequilibrio occlusale nei pazienti affetti da sindrome disfunzionale cranio mandibolare. L'impiego di una placca funzionale.

To elaborate any protocol treatment it is vitally important to start therapy with the aim of resolving the etiological factor in order to avoid the risk of recidivation. For this purpose the stages which have led to the loss of functional equilibrium must be traced backwards. The most striking symptoms of this damage are represented by the altered occlusal ratios, but the etiopathogenesis must be sought not only in occlusal causes but, more often, in dysmorphic, postural or neuro-muscular causes. It is necessary to start working backwards having restored the spatial position of the jaw in all three dimensions. In order to achieve this for the past three years the authors have routinely used an occlusal plate that they have perfected in the treatment of the majority of patients with dysfunctional syndrome of the stomatognathic apparatus. Over 70% of approximately 600 cases referred to the authors during the same period were treated in this way. The choice of these cases was conditioned by the facial typology of patients. In fact, these patients were characterised by a facial typology which tended to be hypo-divergent. This provoked a condition of "mandibular imprisonment" with an occlusal ratio which locks the jaw in a retruded position. This condition is identified by the authors as the factor that triggers the syndrome not only in those patients in which it is clearly possible to diagnose occlusal diagnosis, but also in those cases in which the pathogenetic motive has a number of causes, for example, poor posture and cases of dysmorphosis.(ABSTRACT TRUNCATED AT 250 WORDS)

[Fractures of maxillo-facial bones in children. Our experience]. / Le fratture dello scheletro maxillo-facciale in età pediatrica. Nostra esperienza.

A clinic-statistical study of maxillo-facial fractures in a series of 52 children is reported. This group presents a higher involvement of mandibular body and a low rate M:F than in the literature. Factors responsible for increasing of maxillo-facial traumas in little girls and in school age are analyzed.

Vertebrate homeobox genes.

In the former part of the review the principal available data about Hox genes, their molecular organisation and their expression in vertebrate embryos, with particular emphasis for mammals, are briefly summarized. In the latter part we analysed the expression of four mouse homeobox genes related to two Drosophila genes expressed in the developing head of the fly: Emx1 and Emx2, related to ems, and Otx1 and Otx2, related to otd.

Potential role for a FTZ-F1 steroid receptor superfamily member in the control of Drosophila metamorphosis.

FTZ-F1, a member of the steroid receptor superfamily, has been implicated in the activation of the homeobox segmentation gene fushi tarazu early in Drosophila embryogenesis. We have cloned a developmental isoform of FTZ-F1 and found that it is expressed as a product of the previously identified, midprepupal chromosome puff at 75CD. The 75CD puff occurs in the midst of a period of intense puffing activity that is triggered in response to the steroid hormone ecdysone at the onset of metamorphosis. Indirect immunofluorescent staining for FTZ-F1 on Drosophila polytene chromosomes reveals binding to over 150 chromosomal targets, which include 75CD itself and prominent late prepupal puffs that are predicted to be regulated by midprepupal puff proteins. These results suggest a role for FTZ-F1 as a regulator of insect metamorphosis and underscore the repeated utilization of a regulatory protein for widely separate developmental pathways.

[A case of osteoma of the mandible]. / Considerazioni su di un caso di osteoma della mandibola.

Osteoma is a benign bone tumour with a very slow growth. In the maxillofacial district the paranasal sinuses and the mandible are more frequently involved. This type of tumour is clinically asymptomatic and the signs of its presence are due to the fact that its expansive and centrifugal growth changes the face features. The surgical operation has a double aim: to solve the aesthetic problem and to prevent complications. In fact, obstructions and compressions ab estrinseco may compromise the function of the nearest organs. The aim of our work has been to show a clinical case which is interesting from a clinical, diagnostic and therapeutic point of view.